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Sample records for molecular imaging non-invasive

  1. 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

  2. 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

  3. Non-Invasive Molecular Imaging of Disease Activity in Atherosclerosis

    PubMed Central

    Dweck, Marc R; Aikawa, Elena; Newby, David E; Tarkin, Jason; Rudd, James; Narula, Jagat; Fayad, Zahi A.

    2016-01-01

    Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is therefore shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis and the advantages and challenges posed by these techniques. PMID:27390335

  4. Non-invasive molecular profiling of cancer using photoacoustic imaging of functionalized gold nanorods

    NASA Astrophysics Data System (ADS)

    Shah, Anant J.; Alles, Erwin J.; Box, Carol; Eccles, Suzanne A.; Robinson, Simon P.; deSouza, Nandita; Bamber, Jeffrey C.

    2014-03-01

    Although molecularly targeted cancer therapies have shown great promise, it is now evident that responses are dependent upon the molecular genetic context. Spatial and temporal tumour heterogeneity renders biopsy of solid tumours unsuitable for determining the genetic profile of the disease, making adaptation of appropriate therapy difficult. We have utilized the tunable optical absorption characteristic of gold nanorods to assess the potential of photoacoustics for non-invasive multiplexed molecular imaging. Gold nanorods with resonance peaks at 700nm and 900nm were functionalised with in-house antibodies ICR55 and ICR62, targeted to HER2 and EGFR transmembrane receptors, respectively. Three human squamous carcinoma cell lines (LICR-LON-HN4 expressing high HER2 and low EGFR, LICR-LON-HN3 expressing intermediate levels of HER2 and EGFR and A431 expressing high EGFR and low HER2) were incubated with the targeted nanorods for 24 hours. Cells were then incorporated as simulated tumours in tissue-like phantoms composed of 7.5% gelatin containing 0.5% Intralipid® for optical scattering and imaged at a depth of 2.5 cm, using a new clinical in-house multi-spectral photoacoustic imaging system. Images were obtained from the cell inclusions for wavelengths ranging from 710 to 950 nm at 40 nm intervals, and the mean amplitude of the photoacoustic image was computed for each wavelength, to determine their relative receptor expression levels. The molecular profile of the cells obtained using multi-wavelength photoacoustics had substantial similarity to that obtained using flow cytometry. These preliminary results confirm selective uptake of the functionalised nanorods, which reflects the cellular expression of therapeutically important oncoproteins, and give an indication of the potential of photoacoustics for multiplexed molecular profiling.

  5. Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging

    PubMed Central

    Song, Jiasheng; Cai, Zhengxin; White, Alexander G.; Jin, Tao; Wang, Xiaolei; Kadayakkara, Deepak; Anderson, Carolyn J.; Ambrose, Zandrea

    2015-01-01

    In vivo imaging can provide real-time information and three-dimensional (3D) non-invasive images of deep tissues and organs, including the brain, whilst allowing longitudinal observation of the same animals, thus eliminating potential variation between subjects. Current in vivo imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) and bioluminescence imaging (BLI), can be used to pinpoint the spatial location of target cells, which is urgently needed for revealing human immunodeficiency virus (HIV) dissemination in real-time and HIV-1 reservoirs during suppressive antiretroviral therapy (ART). To demonstrate that in vivo imaging can be used to visualize and quantify simian immunodeficiency virus (SIV)-transduced cells, we genetically engineered SIV to carry different imaging reporters. Based on the expression of the reporter genes, we could visualize and quantify the SIV-transduced cells via vesicular stomatitis virus glycoprotein pseudotyping in a mouse model using BLI, PET-CT or MRI. We also engineered a chimeric EcoSIV for in vivo infection study. Our results demonstrated that BLI is sensitive enough to detect as few as five single cells transduced with virus, whilst PET-CT can provide 3D images of the spatial location of as few as 10 000 SIV-infected cells. We also demonstrated that MRI can provide images with high spatial resolution in a 3D anatomical context to distinguish a small population of SIV-transduced cells. The in vivo imaging platform described here can potentially serve as a powerful tool to visualize lentiviral infection, including when and where viraemia rebounds, and how reservoirs are formed and maintained during latency or suppressive ART. PMID:26297664

  6. Non-invasive molecular imaging of prostate cancer lymph node metastasis

    PubMed Central

    Pouliot, Frédéric; Johnson, Mai; Wu, Lily

    2009-01-01

    Imaging in medicine has been classically based on the anatomical description of organs. In the past 15 years, new imaging techniques based on gene expression that characterize a pathological process have been developed. Molecular imaging is the use of such molecules to image cell-specific characteristics. Here, we review recent advances in molecular imaging, taking as our prime example lymph node (LN) metastasis in prostate cancer. We describe the new techniques and compare their accuracy in detecting LN metastasis in prostate cancer. We also present new molecular strategies for improving tumor detection using adenoviruses, molecular promoters and amplification systems. Finally, we present the concept of ‘in vivo pathology’, which envisages using molecular imaging to accurately localize metastatic lesions based on the molecular signature of the disease. PMID:19482514

  7. In Vivo Non Invasive Molecular Imaging for Immune Cell Tracking in Small Animals

    PubMed Central

    Hong, Kee-Jong

    2012-01-01

    Clinical and preclinical in vivo immune cell imaging approaches have been used to study immune cell proliferation, apoptosis and interaction at the microscopic (intra-vital imaging) and macroscopic (whole-body imaging) level by use of ex vivo or in vivo labeling method. A series of imaging techniques ranging from non-radiation based techniques such as optical imaging, MRI, and ultrasound to radiation based CT/nuclear imaging can be used for in vivo immune cell tracking. These imaging modalities highlight the intrinsic behavior of different immune cell populations in physiological context. Fluorescent, radioactive or paramagnetic probes can be used in direct labeling protocols to monitor the specific cell population. Reporter genes can also be used for genetic, indirect labeling protocols to track the fate of a given cell subpopulation in vivo. In this review, we summarized several methods dealing with dendritic cell, macrophage, and T lymphocyte specifically labeled for different macroscopic wholebody imaging techniques both for the study of their physiological function and in the context of immunotherapy to exploit imaging-derived information and immune-based treatments. PMID:23396713

  8. New Concepts in Molecular Imaging: Non-Invasive MRI Spotting of Proteolysis Using an Overhauser Effect Switch

    PubMed Central

    Mellet, Philippe; Massot, Philippe; Madelin, Guillaume; Marque, Sylvain R. A.; Harte, Etienne; Franconi, Jean-Michel; Thiaudière, Eric

    2009-01-01

    Background Proteolysis, involved in many processes in living organisms, is tightly regulated in space and time under physiological conditions. However deregulation can occur with local persistent proteolytic activities, e.g. in inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is known about the role of many proteases, hence there is a need of new imaging methods to visualize specifically normal or disease-related proteolysis in intact bodies. Methodology/Principal Findings In this paper, a new concept for non invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance Imaging (OMRI) at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon proteolysis due to the associated decrease in the motional correlation time of the substrate. The OMRI experimental device used in this study is consistent with protease imaging in mice at 0.2 T without significant heating. Simulations show that this enzymatic-driven OMRI signal switch can be obtained at lower frequencies suitable for larger animals or humans. Conclusions/Significance The method is highly sensitive and makes possible proteolysis imaging in three dimensions with a good spatial resolution. Any protease could be targeted specifically through the use of taylor-made cleavable macromolecules. At short term OMRI of proteolysis may be applied to basic research as well as to evaluate therapeutic treatments in small animal models of experimental diseases. PMID:19396361

  9. A Preclinical Evaluation of Antrodia camphorata Alcohol Extracts in the Treatment of Non-Small Cell Lung Cancer Using Non-Invasive Molecular Imaging

    PubMed Central

    Chiou, Jeng-Feng; Wu, Alexander T. H.; Wang, Wei-Tin; Kuo, Tsu-Hsiang; Gelovani, Juri G.; Lin, I-Hsin; Wu, Chih-Hsiung; Chiu, Wen-Ta; Deng, Win-Ping

    2011-01-01

    This study was carried out to provide a platform for the pre-clinical evaluation of anti-cancer properties of a unique CAM (complementary and alternative medicine) agent, Antrodia camphorata alcohol extract (ACAE), in a mouse model with the advantageous non-invasive in vivo bioluminescence molecular imaging technology. In vitro analyses on the proliferation, migration/invasion, cell cycle and apoptosis were performed on ACAE-treated non-small cell lung cancer cells, H441GL and control CGL1 cells. In vivo, immune-deficient mice were inoculated subcutaneously with H441GL followed by oral gavages of ACAE. The effect of ACAE on tumor progression was monitored by non-invasive bioluminescence imaging. The proliferation and migration/invasion of H441GL cells were inhibited by ACAE in a dose-dependent manner. In addition, ACAE induced cell cycle arrest at G0/G1 phase and apoptosis in H441GL cells as shown by flow cytometric analysis, Annexin-V immunoflourescence and DNA fragmentation. In vivo bioluminescence imaging revealed that tumorigenesis was significantly retarded by oral treatment of ACAE in a dose-dependent fashion. Based on our experimental data, ACAE contains anti-cancer properties and could be considered as a potential CAM agent in future clinical evaluation. PMID:21785640

  10. Non-invasive imaging through opaque scattering layers.

    PubMed

    Bertolotti, Jacopo; van Putten, Elbert G; Blum, Christian; Lagendijk, Ad; Vos, Willem L; Mosk, Allard P

    2012-11-08

    Non-invasive optical imaging techniques, such as optical coherence tomography, are essential diagnostic tools in many disciplines, from the life sciences to nanotechnology. However, present methods are not able to image through opaque layers that scatter all the incident light. Even a very thin layer of a scattering material can appear opaque and hide any objects behind it. Although great progress has been made recently with methods such as ghost imaging and wavefront shaping, present procedures are still invasive because they require either a detector or a nonlinear material to be placed behind the scattering layer. Here we report an optical method that allows non-invasive imaging of a fluorescent object that is completely hidden behind an opaque scattering layer. We illuminate the object with laser light that has passed through the scattering layer. We scan the angle of incidence of the laser beam and detect the total fluorescence of the object from the front. From the detected signal, we obtain the image of the hidden object using an iterative algorithm. As a proof of concept, we retrieve a detailed image of a fluorescent object, comparable in size (50 micrometres) to a typical human cell, hidden 6 millimetres behind an opaque optical diffuser, and an image of a complex biological sample enclosed between two opaque screens. This approach to non-invasive imaging through strongly scattering media can be generalized to other contrast mechanisms and geometries.

  11. Non-invasive Imaging of Colitis using Multispectral Optoacoustic Tomography.

    PubMed

    Bhutiani, Neal; Grizzle, William E; Galandiuk, Susan; Otali, Denis; Dryden, Gerald W; Egilmez, Nejat K; McNally, Lacey R

    2016-12-01

    Currently, several non-invasive modalities, including MRI and PET, are being investigated to identify early intestinal inflammation, longitudinally monitor disease status, or detect dysplastic changes in patients with inflammatory bowel disease (IBD). Here, we assess the applicability and utility of multispectral optoacoustic tomography (MSOT) in evaluating the presence and severity of colitis. Mice with bacterial colitis demonstrated a temporally associated increase in mesenteric and colonic vascularity with an increase in mean signal intensity of oxygenated hemoglobin (p=0.004) by MSOT two days after inoculation. These findings were significantly more prominent 7 days after inoculation, with increased mean signal intensity of oxygenated hemoglobin (p=0.0002) and the development of punctate vascular lesions on the colonic surface, which corresponded to changes observed on colonoscopy as well as histology. With improvements in depth of tissue penetration, MSOT may hold potential as a sensitive, accurate, non-invasive imaging tool in evaluation of patients with IBD.

  12. Non-invasive assessment of the liver using imaging

    NASA Astrophysics Data System (ADS)

    Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.

    2016-12-01

    Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.

  13. Non-invasive diagnostic imaging of colorectal liver metastases

    PubMed Central

    Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone

    2015-01-01

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs. PMID:26217455

  14. Non-invasive diagnostic imaging of colorectal liver metastases.

    PubMed

    Mainenti, Pier Paolo; Romano, Federica; Pizzuti, Laura; Segreto, Sabrina; Storto, Giovanni; Mannelli, Lorenzo; Imbriaco, Massimo; Camera, Luigi; Maurea, Simone

    2015-07-28

    Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.

  15. Non-invasive imaging of microcirculation: a technology review.

    PubMed

    Eriksson, Sam; Nilsson, Jan; Sturesson, Christian

    2014-01-01

    Microcirculation plays a crucial role in physiological processes of tissue oxygenation and nutritional exchange. Measurement of microcirculation can be applied on many organs in various pathologies. In this paper we aim to review the technique of non-invasive methods for imaging of the microcirculation. Methods covered are: videomicroscopy techniques, laser Doppler perfusion imaging, and laser speckle contrast imaging. Videomicroscopy techniques, such as orthogonal polarization spectral imaging and sidestream dark-field imaging, provide a plentitude of information and offer direct visualization of the microcirculation but have the major drawback that they may give pressure artifacts. Both laser Doppler perfusion imaging and laser speckle contrast imaging allow non-contact measurements but have the disadvantage of their sensitivity to motion artifacts and that they are confined to relative measurement comparisons. Ideal would be a non-contact videomicroscopy method with fully automatic analysis software.

  16. Advances in non-invasive imaging of intracranial vascular disease.

    PubMed Central

    Jäger, H. R.; Grieve, J. P.

    2000-01-01

    Intra-arterial catheter angiography has, in the past, been the mainstay for the investigation of intracranial vascular disease. It is, however, invasive, usually requires in-patients admission, and is associated with a rate of neurological complications between 1% and 3%. In recent years, magnetic resonance angiography (MRA) and CT angiography (CTA) have emerged as non-invasive alternatives for imaging blood vessels and have made a significant impact on neuroradiological investigations. It is the purpose of this article to explain the basic technical principles of these two methods and to give an overview of their current clinical applications. PMID:10700757

  17. [Hybrid imaging: present and future of non-invasive diagnosis].

    PubMed

    Panetta, Daniele; Marinelli, Martina; Todiere, Giancarlo; Tripodi, Maria; Salvadori, Piero A; Neglia, Danilo

    2012-05-01

    The integration of complementary information from different medical imaging techniques opened, since the 90s, new scenarios and possibilities for non-invasive diagnosis. The anatomo-functional information obtained with the image fusion (i.e., by composing PET and CT or SPECT and CT), is greater than the sum of information given by each modality, and allows quantitative evaluation of functional parameters through the application of specific model-based image processing. Before the introduction of integrated multimodal scanners from most manufacturers (hardware fusion), many software techniques have been used to allow image fusion from different modalities; such methods of software fusion is still important for all modalities that cannot by merged in a single scanner, or whenever the patient movement can introduce inter-modality misalignments within the same exam in an integrated scanner or if each modality is utilized at different times and on separate scanners. This article summarizes the software and hardware evolution of clinical and preclinical hybrid imaging, and discusses the outcome of this technology in the clinical environment with particular emphasis on the cardiovascular application.

  18. Mouse models in neurological disorders: applications of non-invasive imaging.

    PubMed

    Waerzeggers, Yannic; Monfared, Parisa; Viel, Thomas; Winkeler, Alexandra; Jacobs, Andreas H

    2010-10-01

    Neuroimaging techniques represent powerful tools to assess disease-specific cellular, biochemical and molecular processes non-invasively in vivo. Besides providing precise anatomical localisation and quantification, the most exciting advantage of non-invasive imaging techniques is the opportunity to investigate the spatial and temporal dynamics of disease-specific functional and molecular events longitudinally in intact living organisms, so called molecular imaging (MI). Combining neuroimaging technologies with in vivo models of neurological disorders provides unique opportunities to understand the aetiology and pathophysiology of human neurological disorders. In this way, neuroimaging in mouse models of neurological disorders not only can be used for phenotyping specific diseases and monitoring disease progression but also plays an essential role in the development and evaluation of disease-specific treatment approaches. In this way MI is a key technology in translational research, helping to design improved disease models as well as experimental treatment protocols that may afterwards be implemented into clinical routine. The most widely used imaging modalities in animal models to assess in vivo anatomical, functional and molecular events are positron emission tomography (PET), magnetic resonance imaging (MRI) and optical imaging (OI). Here, we review the application of neuroimaging in mouse models of neurodegeneration (Parkinson's disease, PD, and Alzheimer's disease, AD) and brain cancer (glioma).

  19. Autoimmune pancreatitis: Multimodality non-invasive imaging diagnosis

    PubMed Central

    Crosara, Stefano; D'Onofrio, Mirko; De Robertis, Riccardo; Demozzi, Emanuele; Canestrini, Stefano; Zamboni, Giulia; Pozzi Mucelli, Roberto

    2014-01-01

    Autoimmune pancreatitis (AIP) is characterized by obstructive jaundice, a dramatic clinical response to steroids and pathologically by a lymphoplasmacytic infiltrate, with or without a pancreatic mass. Type 1 AIP is the pancreatic manifestation of an IgG4-related systemic disease and is characterized by elevated IgG4 serum levels, infiltration of IgG4-positive plasma cells and extrapancreatic lesions. Type 2 AIP usually has none or very few IgG4-positive plasma cells, no serum IgG4 elevation and appears to be a pancreas-specific disorder without extrapancreatic involvement. AIP is diagnosed in approximately 2%-6% of patients that undergo pancreatic resection for suspected pancreatic cancer. There are three patterns of autoimmune pancreatitis: diffuse disease is the most common type, with a diffuse, “sausage-like” pancreatic enlargement with sharp margins and loss of the lobular contours; focal disease is less common and manifests as a focal mass, often within the pancreatic head, mimicking a pancreatic malignancy. Multifocal involvement can also occur. In this paper we describe the features of AIP at ultrasonography, computed tomography, magnetic resonance and positron emission tomography/computed tomography imaging, focusing on diagnosis and differential diagnosis with pancreatic ductal adenocarcinoma. It is of utmost importance to make an early correct differential diagnosis between these two diseases in order to identify the optimal therapeutic strategy and to avoid unnecessary laparotomy or pancreatic resection in AIP patients. Non-invasive imaging plays also an important role in therapy monitoring, in follow-up and in early identification of disease recurrence. PMID:25493001

  20. Diagnostic and prognostic utility of non-invasive imaging in diabetes management

    PubMed Central

    Barsanti, Cristina; Lenzarini, Francesca; Kusmic, Claudia

    2015-01-01

    Medical imaging technologies are acquiring an increasing relevance to assist clinicians in diagnosis and to guide management and therapeutic treatment of patients, thanks to their non invasive and high resolution properties. Computed tomography, magnetic resonance imaging, and ultrasonography are the most used imaging modalities to provide detailed morphological reconstructions of tissues and organs. In addition, the use of contrast dyes or radionuclide-labeled tracers permits to get functional and quantitative information about tissue physiology and metabolism in normal and disease state. In recent years, the development of multimodal and hydrid imaging techniques is coming to be the new frontier of medical imaging for the possibility to overcome limitations of single modalities and to obtain physiological and pathophysiological measurements within an accurate anatomical framework. Moreover, the employment of molecular probes, such as ligands or antibodies, allows a selective in vivo targeting of biomolecules involved in specific cellular processes, so expanding the potentialities of imaging techniques for clinical and research applications. This review is aimed to give a survey of characteristics of main diagnostic non-invasive imaging techniques. Current clinical appliances and future perspectives of imaging in the diagnostic and prognostic assessment of diabetic complications affecting different organ systems will be particularly addressed. PMID:26131322

  1. Estimating Trabecular Bone Mechanical Properties From Non-Invasive Imaging

    NASA Technical Reports Server (NTRS)

    Hogan, Harry A.; Webster, Laurie

    1997-01-01

    An important component in developing countermeasures for maintaining musculoskeletal integrity during long-term space flight is an effective and meaningful method of monitoring skeletal condition. Magnetic resonance imaging (MRI) is an attractive non-invasive approach because it avoids the exposure to radiation associated with X-ray based imaging and also provides measures related to bone microstructure rather than just density. The purpose of the research for the 1996 Summer Faculty Fellowship period was to extend the usefulness of the MRI data to estimate the mechanical properties of trabecular bone. The main mechanical properties of interest are the elastic modulus and ultimate strength. Correlations are being investigated between these and fractal analysis parameters, MRI relaxation times, apparent densities, and bone mineral densities. Bone specimens from both human and equine donors have been studied initially to ensure high-quality MR images. Specimens were prepared and scanned from human proximal tibia bones as well as the equine distal radius. The quality of the images from the human bone appeared compromised due to freezing artifact, so only equine bone was included in subsequent procedures since these specimens could be acquired and imaged fresh before being frozen. MRI scans were made spanning a 3.6 cm length on each of 5 equine distal radius specimens. The images were then sent to Dr. Raj Acharya of the State University of New York at Buffalo for fractal analysis. Each piece was cut into 3 slabs approximately 1.2 cm thick and high-resolution contact radiographs were made to provide images for comparing fractal analysis with MR images. Dual energy X-ray absorptiometry (DEXA) scans were also made of each slab for subsequent bone mineral density determination. Slabs were cut into cubes for mechanical using a slow-speed diamond blade wafering saw (Buehler Isomet). The dimensions and wet weights of each cube specimen were measured and recorded. Wet weights

  2. Non-invasive multiphoton imaging of extracellular matrix structures

    PubMed Central

    Schenke-Layland, Katja

    2015-01-01

    Multiphoton microscopy has become a powerful method for the artifact-free, nondestructive evaluation of deep-tissue cells and extracellular matrix (ECM) structures in their native environment. By interacting with highly non-centrosymmetric molecular assemblies such as fibrillar collagen, the non-linear process called second harmonic generation (SHG) has also proven to be an important diagnostic tool for the visualization of ECM compartments in situ with submicron resolution without the need for tissue processing. This review reports on applications of multiphoton-induced autofluorescence and SHG microscopy to identify collagen and elastic fiber orientation in native, tissue-engineered and processed, as well as healthy and diseased, tissues and organs. SHG signal profiling was used to quantify ECM damage in various cardiovascular and exocrine tissues, as well as cartilage. These novel imaging modalities open the general possibility of high-resolution in situ and more important in vivo imaging of ECM structures, cells and intracellular organelles in living intact tissues. Heart valve leaflets have a unique extracellular matrix that is organized in distinct layers, which can be non-destructively visualized by multiphoton imaging. PMID:19343671

  3. Retinal functional imager (RFI): non-invasive functional imaging of the retina.

    PubMed

    Ganekal, S

    2013-01-01

    Retinal functional imager (RFI) is a unique non-invasive functional imaging system with novel capabilities for visualizing the retina. The objective of this review was to show the utility of non-invasive functional imaging in various disorders. Electronic literature search was carried out using the websites www.pubmed.gov and www.google.com. The search words were retinal functional imager and non-invasive retinal imaging used in combination. The articles published or translated into English were studied. The RFI directly measures hemodynamic parameters such as retinal blood-flow velocity, oximetric state, metabolic responses to photic activation and generates capillary perfusion maps (CPM) that provides retinal vasculature detail similar to flourescein angiography. All of these parameters stand in a direct relationship to the function and therefore the health of the retina, and are known to be degraded in the course of retinal diseases. Detecting changes in retinal function aid early diagnosis and treatment as functional changes often precede structural changes in many retinal disorders.

  4. Quantitative molecular sensing in biological tissues: an approach to non-invasive optical characterization

    NASA Astrophysics Data System (ADS)

    Chandra, Malavika; Vishwanath, Karthik; Fichter, Greg D.; Liao, Elly; Hollister, Scott J.; Mycek, Mary-Ann

    2006-06-01

    A method to non-invasively and quantitatively characterize thick biological tissues by combining both experimental and computational approaches in tissue optical spectroscopy was developed and validated on fifteen porcine articular cartilage (AC) tissue samples. To the best of our knowledge, this study is the first to couple non-invasive reflectance and fluorescence spectroscopic measurements on freshly harvested tissues with Monte Carlo computational modeling of time-resolved propagation of both excitation light and multi-fluorophore emission. For reflectance, quantitative agreement between simulation and experiment was achieved to better than 11%. Fluorescence data and simulations were used to extract the ratio of the absorption coefficients of constituent fluorophores for each measured AC tissue sample. This ratio could be used to monitor relative changes in concentration of the constituent fluorophores over time. The samples studied possessed the complexity and variability not found in artificial tissue-simulating phantoms and serve as a model for future optical molecular sensing studies on tissue engineered constructs intended for use in human therapeutics. An optical technique that could non-invasively and quantitatively assess soft tissue composition or physiologic status would represent a significant advance in tissue engineering. Moreover, the general approach described here for optical characterization should be broadly applicable to quantitative, non-invasive molecular sensing applications in complex, three-dimensional biological tissues.

  5. Non-invasive Imaging of Idiopathic Pulmonary Fibrosis Using Cathepsin Protease Probes.

    PubMed

    Withana, Nimali P; Ma, Xiaowei; McGuire, Helen M; Verdoes, Martijn; van der Linden, Wouter A; Ofori, Leslie O; Zhang, Ruiping; Li, Hao; Sanman, Laura E; Wei, Ke; Yao, Shaobo; Wu, Peilin; Li, Fang; Huang, Hui; Xu, Zuojun; Wolters, Paul J; Rosen, Glenn D; Collard, Harold R; Zhu, Zhaohui; Cheng, Zhen; Bogyo, Matthew

    2016-01-22

    Idiopathic pulmonary fibrosis (IPF) is a lethal, chronic, progressive disease characterized by formation of scar tissue within the lungs. Because it is a disease of unknown etiology, it is difficult to diagnose, to predict disease course and to devise treatment strategies. Recent evidence suggests that activated macrophages play key roles in the pathology of IPF. Therefore, imaging probes that specifically recognize these pools of activated immune cells could provide valuable information about how these cells contribute to the pathobiology of the disease. Here we demonstrate that cysteine cathepsin-targeted imaging probes can be used to monitor the contribution of macrophages to fibrotic disease progression in the bleomycin-induced murine model of pulmonary fibrosis. Furthermore, we show that the probes highlight regions of macrophage involvement in fibrosis in human biopsy tissues from IPF patients. Finally, we present first-in-human results demonstrating non-invasive imaging of active cathepsins in fibrotic lesions of patients with IPF. Together, our findings validate small molecule cysteine cathepsin probes for clinical PET imaging and suggest that they have the potential to be used to generate mechanistically-informative molecular information regarding cellular drivers of IPF disease severity and progression.

  6. Non-invasive imaging of skin cancer with fluorescence lifetime imaging using two photon tomography

    NASA Astrophysics Data System (ADS)

    Patalay, Rakesh; Talbot, Clifford; Alexandrov, Yuriy; Munro, Ian; Breunig, Hans Georg; König, Karsten; Warren, Sean; Neil, Mark A. A.; French, Paul M. W.; Chu, Anthony; Stamp, Gordon W.; Dunsby, Christopher

    2011-07-01

    Multispectral fluorescence lifetime imaging (FLIM) using two photon microscopy as a non-invasive technique for the diagnosis of skin lesions is described. Skin contains fluorophores including elastin, keratin, collagen, FAD and NADH. This endogenous contrast allows tissue to be imaged without the addition of exogenous agents and allows the in vivo state of cells and tissues to be studied. A modified DermaInspect® multiphoton tomography system was used to excite autofluorescence at 760 nm in vivo and on freshly excised ex vivo tissue. This instrument simultaneously acquires fluorescence lifetime images in four spectral channels between 360-655 nm using time-correlated single photon counting and can also provide hyperspectral images. The multispectral fluorescence lifetime images were spatially segmented and binned to determine lifetimes for each cell by fitting to a double exponential lifetime model. A comparative analysis between the cellular lifetimes from different diagnoses demonstrates significant diagnostic potential.

  7. Non-invasive imaging using reporter genes altering cellular water permeability

    NASA Astrophysics Data System (ADS)

    Mukherjee, Arnab; Wu, Di; Davis, Hunter C.; Shapiro, Mikhail G.

    2016-12-01

    Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.

  8. Imaging and finite element analysis: a methodology for non-invasive characterization of aortic tissue.

    PubMed

    Flamini, Vittoria; Creane, Arthur P; Kerskens, Christian M; Lally, Caitríona

    2015-01-01

    Characterization of the mechanical properties of arterial tissues usually involves an invasive procedure requiring tissue removal. In this work we propose a non-invasive method to perform a biomechanical analysis of cardiovascular aortic tissue. This method is based on combining medical imaging and finite element analysis (FEA). Magnetic resonance imaging (MRI) was chosen since it presents relatively low risks for human health. A finite element model was created from the MRI images and loaded with systolic physiological pressures. By means of an optimization routine, the structural material properties were changed until average strains matched those measured by MRI. The method outlined in this work produced an estimate of the in situ properties of cardiovascular tissue based on non-invasive image datasets and finite element analysis.

  9. Non-invasive imaging using reporter genes altering cellular water permeability.

    PubMed

    Mukherjee, Arnab; Wu, Di; Davis, Hunter C; Shapiro, Mikhail G

    2016-12-23

    Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.

  10. Hyperspectral imaging coupled with chemometric analysis for non-invasive differentiation of black pens

    NASA Astrophysics Data System (ADS)

    Chlebda, Damian K.; Majda, Alicja; Łojewski, Tomasz; Łojewska, Joanna

    2016-11-01

    Differentiation of the written text can be performed with a non-invasive and non-contact tool that connects conventional imaging methods with spectroscopy. Hyperspectral imaging (HSI) is a relatively new and rapid analytical technique that can be applied in forensic science disciplines. It allows an image of the sample to be acquired, with full spectral information within every pixel. For this paper, HSI and three statistical methods (hierarchical cluster analysis, principal component analysis, and spectral angle mapper) were used to distinguish between traces of modern black gel pen inks. Non-invasiveness and high efficiency are among the unquestionable advantages of ink differentiation using HSI. It is also less time-consuming than traditional methods such as chromatography. In this study, a set of 45 modern gel pen ink marks deposited on a paper sheet were registered. The spectral characteristics embodied in every pixel were extracted from an image and analysed using statistical methods, externally and directly on the hypercube. As a result, different black gel inks deposited on paper can be distinguished and classified into several groups, in a non-invasive manner.

  11. Characterization of the Tumor Microenvironment and Tumor–Stroma Interaction by Non-invasive Preclinical Imaging

    PubMed Central

    Ramamonjisoa, Nirilanto; Ackerstaff, Ellen

    2017-01-01

    Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression. The resulting altered metabolic content in tumors has the ability to affect cell signaling and block cellular differentiation. Additional emerging evidence reveals that the interaction between tumor and stroma cells can alter tumor metabolism (leading to metabolic reprograming) as well as tumor growth and vascular features. This review will summarize previous and current preclinical, non-invasive, multimodal imaging efforts to characterize the tumor microenvironment, including its stromal components and understand tumor–stroma interaction in cancer development, progression, and treatment response. PMID:28197395

  12. Multispectral retinal image analysis: a novel non-invasive tool for retinal imaging

    PubMed Central

    Calcagni, A; Gibson, J M; Styles, I B; Claridge, E; Orihuela-Espina, F

    2011-01-01

    Purpose To develop a non-invasive method for quantification of blood and pigment distributions across the posterior pole of the fundus from multispectral images using a computer-generated reflectance model of the fundus. Methods A computer model was developed to simulate light interaction with the fundus at different wavelengths. The distribution of macular pigment (MP) and retinal haemoglobins in the fundus was obtained by comparing the model predictions with multispectral image data at each pixel. Fundus images were acquired from 16 healthy subjects from various ethnic backgrounds and parametric maps showing the distribution of MP and of retinal haemoglobins throughout the posterior pole were computed. Results The relative distributions of MP and retinal haemoglobins in the subjects were successfully derived from multispectral images acquired at wavelengths 507, 525, 552, 585, 596, and 611 nm, providing certain conditions were met and eye movement between exposures was minimal. Recovery of other fundus pigments was not feasible and further development of the imaging technique and refinement of the software are necessary to understand the full potential of multispectral retinal image analysis. Conclusion The distributions of MP and retinal haemoglobins obtained in this preliminary investigation are in good agreement with published data on normal subjects. The ongoing development of the imaging system should allow for absolute parameter values to be computed. A further study will investigate subjects with known pathologies to determine the effectiveness of the method as a screening and diagnostic tool. PMID:21904394

  13. Multispectral retinal image analysis: a novel non-invasive tool for retinal imaging.

    PubMed

    Calcagni, A; Gibson, J M; Styles, I B; Claridge, E; Orihuela-Espina, F

    2011-12-01

    To develop a non-invasive method for quantification of blood and pigment distributions across the posterior pole of the fundus from multispectral images using a computer-generated reflectance model of the fundus. A computer model was developed to simulate light interaction with the fundus at different wavelengths. The distribution of macular pigment (MP) and retinal haemoglobins in the fundus was obtained by comparing the model predictions with multispectral image data at each pixel. Fundus images were acquired from 16 healthy subjects from various ethnic backgrounds and parametric maps showing the distribution of MP and of retinal haemoglobins throughout the posterior pole were computed. The relative distributions of MP and retinal haemoglobins in the subjects were successfully derived from multispectral images acquired at wavelengths 507, 525, 552, 585, 596, and 611 nm, providing certain conditions were met and eye movement between exposures was minimal. Recovery of other fundus pigments was not feasible and further development of the imaging technique and refinement of the software are necessary to understand the full potential of multispectral retinal image analysis. The distributions of MP and retinal haemoglobins obtained in this preliminary investigation are in good agreement with published data on normal subjects. The ongoing development of the imaging system should allow for absolute parameter values to be computed. A further study will investigate subjects with known pathologies to determine the effectiveness of the method as a screening and diagnostic tool.

  14. A REVIEW OF NON-INVASIVE IMAGING METHODS AND APPLICATIONS IN CONTAMINANT HYDROGEOLOGY RESEARCH

    SciTech Connect

    Werth, Charles J.; Zhang, Changyong; Brusseau, M. L.; Oostrom, Martinus; Baumann, T.

    2010-03-08

    Contaminant hydrogeological processes occurring in porous media are typically not amenable to direct observation. As a result, indirect measurements (e.g., contaminant breakthrough at a fixed location) are often used to infer processes occurring at different scales, locations, or times. To overcome this limitation, non-invasive imaging methods are increasingly being used in contaminant hydrogeology research. The most common methods, and the subjects of this review, are optical imaging using UV or visible light, dual-energy gamma-radiation, X-ray microtomography, and magnetic resonance imaging (MRI). Non-invasive imaging techniques have provided valuable insights into a variety of complex systems and processes, including porous media characterization, multiphase fluid distribution, fluid flow, solute transport and mixing, colloidal transport and deposition, and reactions. In this paper we review the theory underlying these methods, applications of these methods to contaminant hydrogeology research, and methods’ advantages and disadvantages. As expected, there is no perfect method or tool for non-invasive imaging. However, optical methods generally present the least expensive and easiest options for imaging fluid distribution, solute and fluid flow, colloid transport, and reactions in artificial two-dimensional (2D) porous media. Gamma radiation methods present the best opportunity for characterization of fluid distributions in 2D at the Darcy scale. X-ray methods present the highest resolution and flexibility for three-dimensional (3D) natural porous media characterization, and 3D characterization of fluid distributions in natural porous media. And MRI presents the best option for 3D characterization of fluid distribution, fluid flow, colloid transport, and reaction in artificial porous media. Obvious deficiencies ripe for method development are the ability to image transient processes such as fluid flow and colloid transport in natural porous media in three

  15. A review of non-invasive imaging methods and applications in contaminant hydrogeology research.

    PubMed

    Werth, Charles J; Zhang, Changyong; Brusseau, Mark L; Oostrom, Mart; Baumann, Thomas

    2010-04-01

    Contaminant hydrogeological processes occurring in porous media are typically not amenable to direct observation. As a result, indirect measurements (e.g., contaminant breakthrough at a fixed location) are often used to infer processes occurring at different scales, locations, or times. To overcome this limitation, non-invasive imaging methods are increasingly being used in contaminant hydrogeology research. Four of the most common methods, and the subjects of this review, are optical imaging using UV or visible light, dual-energy gamma radiation, X-ray microtomography, and magnetic resonance imaging (MRI). Non-invasive imaging techniques have provided valuable insights into a variety of complex systems and processes, including porous media characterization, multiphase fluid distribution, fluid flow, solute transport and mixing, colloidal transport and deposition, and reactions. In this paper we review the theory underlying these methods, applications of these methods to contaminant hydrogeology research, and methods' advantages and disadvantages. As expected, there is no perfect method or tool for non-invasive imaging. However, optical methods generally present the least expensive and easiest options for imaging fluid distribution, solute and fluid flow, colloid transport, and reactions in artificial two-dimensional (2D) porous media. Gamma radiation methods present the best opportunity for characterization of fluid distributions in 2D at the Darcy scale. X-ray methods present the highest resolution and flexibility for three-dimensional (3D) natural porous media characterization, and 3D characterization of fluid distributions in natural porous media. And MRI presents the best option for 3D characterization of fluid distribution, fluid flow, colloid transport, and reaction in artificial porous media. Obvious deficiencies ripe for method development are the ability to image transient processes such as fluid flow and colloid transport in natural porous media in three

  16. Scanning superlens microscopy for non-invasive large field-of-view visible light nanoscale imaging

    NASA Astrophysics Data System (ADS)

    Wang, Feifei; Liu, Lianqing; Yu, Haibo; Wen, Yangdong; Yu, Peng; Liu, Zhu; Wang, Yuechao; Li, Wen Jung

    2016-12-01

    Nanoscale correlation of structural information acquisition with specific-molecule identification provides new insight for studying rare subcellular events. To achieve this correlation, scanning electron microscopy has been combined with super-resolution fluorescent microscopy, despite its destructivity when acquiring biological structure information. Here we propose time-efficient non-invasive microsphere-based scanning superlens microscopy that enables the large-area observation of live-cell morphology or sub-membrane structures with sub-diffraction-limited resolution and is demonstrated by observing biological and non-biological objects. This microscopy operates in both non-invasive and contact modes with ~200 times the acquisition efficiency of atomic force microscopy, which is achieved by replacing the point of an atomic force microscope tip with an imaging area of microspheres and stitching the areas recorded during scanning, enabling sub-diffraction-limited resolution. Our method marks a possible path to non-invasive cell imaging and simultaneous tracking of specific molecules with nanoscale resolution, facilitating the study of subcellular events over a total cell period.

  17. Non-invasive near-infrared fluorescence imaging of the neutrophil response in a mouse model of transient cerebral ischaemia.

    PubMed

    Vaas, Markus; Enzmann, Gaby; Perinat, Therese; Siler, Ulrich; Reichenbach, Janine; Licha, Kai; Kipar, Anja; Rudin, Markus; Engelhardt, Britta; Klohs, Jan

    2016-10-27

    Near-infrared fluorescence (NIRF) imaging enables non-invasive monitoring of molecular and cellular processes in live animals. Here we demonstrate the suitability of NIRF imaging to investigate the neutrophil response in the brain after transient middle cerebral artery occlusion (tMCAO). We established procedures for ex vivo fluorescent labelling of neutrophils without affecting their activation status. Adoptive transfer of labelled neutrophils in C57BL/6 mice before surgery resulted in higher fluorescence intensities over the ischaemic hemisphere in tMCAO mice with NIRF imaging when compared with controls, corroborated by ex vivo detection of labelled neutrophils using fluorescence microscopy. NIRF imaging showed that neutrophils started to accumulate immediately after tMCAO, peaking at 18 h, and were still visible until 48 h after reperfusion. Our data revealed accumulation of neutrophils also in extracranial tissue, indicating damage in the external carotid artery territory in the tMCAO model. Antibody-mediated inhibition of α4-integrins did reduce fluorescence signals at 18 and 24, but not at 48 h after reperfusion, compared with control treatment animals. Antibody treatment reduced cerebral lesion volumes by 19%. In conclusion, the non-invasive nature of NIRF imaging allows studying the dynamics of neutrophil recruitment and its modulation by targeted interventions in the mouse brain after transient experimental cerebral ischaemia.

  18. Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared fluorescence and positron-emission tomography

    PubMed Central

    Page, Michael J.; Lourenço, André L.; David, Tovo; LeBeau, Aaron M.; Cattaruzza, Fiore; Castro, Helena C.; VanBrocklin, Henry F.; Coughlin, Shaun R.; Craik, Charles S.

    2015-01-01

    Functional imaging of proteolytic activity is an emerging strategy to quantify disease and response to therapy at the molecular level. We present a new peptide-based imaging probe technology that advances these goals by exploiting enzymatic activity to deposit probes labelled with near-infrared (NIR) fluorophores or radioisotopes in cell membranes of disease-associated proteolysis. This strategy allows for non-invasive detection of protease activity in vivo and ex vivo by tracking deposited probes in tissues. We demonstrate non-invasive detection of thrombin generation in a murine model of pulmonary embolism using our protease-activated peptide probes in microscopic clots within the lungs with NIR fluorescence optical imaging and positron-emission tomography. Thrombin activity is imaged deep in tissue and tracked predominantly to platelets within the lumen of blood vessels. The modular design of our probes allows for facile investigation of other proteases, and their contributions to disease by tailoring the protease activation and cell-binding elements. PMID:26423607

  19. Chromatibody, a novel non-invasive molecular tool to explore and manipulate chromatin in living cells

    PubMed Central

    Jullien, Denis; Vignard, Julien; Fedor, Yoann; Béry, Nicolas; Olichon, Aurélien; Crozatier, Michèle; Erard, Monique; Cassard, Hervé; Ducommun, Bernard; Salles, Bernard

    2016-01-01

    ABSTRACT Chromatin function is involved in many cellular processes, its visualization or modification being essential in many developmental or cellular studies. Here, we present the characterization of chromatibody, a chromatin-binding single-domain, and explore its use in living cells. This non-intercalating tool specifically binds the heterodimer of H2A–H2B histones and displays a versatile reactivity, specifically labeling chromatin from yeast to mammals. We show that this genetically encoded probe, when fused to fluorescent proteins, allows non-invasive real-time chromatin imaging. Chromatibody is a dynamic chromatin probe that can be modulated. Finally, chromatibody is an efficient tool to target an enzymatic activity to the nucleosome, such as the DNA damage-dependent H2A ubiquitylation, which can modify this epigenetic mark at the scale of the genome and result in DNA damage signaling and repair defects. Taken together, these results identify chromatibody as a universal non-invasive tool for either in vivo chromatin imaging or to manipulate the chromatin landscape. PMID:27206857

  20. Molecular Diagnostic Trends in Urological Cancer: Biomarkers for Non-Invasive Diagnosis

    PubMed Central

    Urquidi, V.; Rosser, C. J.; Goodison, S.

    2012-01-01

    The early detection of urological cancers is pivotal for successful patient treatment and management. The development of molecular assays that can diagnose disease accurately, or that can augment current methods of evaluation, would be a significant advance. Ideally, such molecular assays would be applicable to non-invasively obtained body fluids, enabling not only diagnosis of at risk patients, but also asymptomatic screening, monitoring disease recurrence and response to treatment. The advent of advanced proteomics and genomics technologies and associated bioinformatics development is bringing these goals into focus. In this article we will discuss the promise of biomarkers in urinalysis for the detection and clinical evaluation of the major urological cancers, including bladder, kidney and prostate. The development of urine-based tests to detect urological cancers would be of tremendous benefit to both patients and the healthcare system. PMID:22680923

  1. Molecular diagnostic trends in urological cancer: biomarkers for non-invasive diagnosis.

    PubMed

    Urquidi, V; Rosser, C J; Goodison, S

    2012-01-01

    The early detection of urological cancers is pivotal for successful patient treatment and management. The development of molecular assays that can diagnose disease accurately, or that can augment current methods of evaluation, would be a significant advance. Ideally, such molecular assays would be applicable to non-invasively obtained body fluids, enabling not only diagnosis of at risk patients, but also asymptomatic screening, monitoring disease recurrence and response to treatment. The advent of advanced proteomics and genomics technologies and associated bioinformatics development is bringing these goals into focus. In this article we will discuss the promise of biomarkers in urinalysis for the detection and clinical evaluation of the major urological cancers, including bladder, kidney and prostate. The development of urine-based tests to detect urological cancers would be of tremendous benefit to both patients and the healthcare system.

  2. Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines

    NASA Astrophysics Data System (ADS)

    Zhang, Yumiao; Jeon, Mansik; Rich, Laurie J.; Hong, Hao; Geng, Jumin; Zhang, Yin; Shi, Sixiang; Barnhart, Todd E.; Alexandridis, Paschalis; Huizinga, Jan D.; Seshadri, Mukund; Cai, Weibo; Kim, Chulhong; Lovell, Jonathan F.

    2014-08-01

    There is a need for safer and improved methods for non-invasive imaging of the gastrointestinal tract. Modalities based on X-ray radiation, magnetic resonance and ultrasound suffer from limitations with respect to safety, accessibility or lack of adequate contrast. Functional intestinal imaging of dynamic gut processes has not been practical using existing approaches. Here, we report the development of a family of nanoparticles that can withstand the harsh conditions of the stomach and intestine, avoid systemic absorption, and provide good optical contrast for photoacoustic imaging. The hydrophobicity of naphthalocyanine dyes was exploited to generate purified ∼20 nm frozen micelles, which we call nanonaps, with tunable and large near-infrared absorption values (>1,000). Unlike conventional chromophores, nanonaps exhibit non-shifting spectra at ultrahigh optical densities and, following oral administration in mice, passed safely through the gastrointestinal tract. Non-invasive, non-ionizing photoacoustic techniques were used to visualize nanonap intestinal distribution with low background and remarkable resolution, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole-body imaging.

  3. Non-invasive imaging of apoptosis and its application in cancer therapeutics

    PubMed Central

    Coppola, Julia M.; Ross, Brian D.; Rehemtulla, Alnawaz

    2009-01-01

    Purpose Activation of the apoptotic cascade plays an important role in the response of tumors to therapy. Non-invasive imaging of apoptosis facilitates optimization of therapeutic protocols regarding dosing and schedule, and enables identification of efficacious combination therapies. Experimental Design We describe a hybrid polypeptide that reports on caspase-3 activity in living cells and animals in a non-invasive manner. This reporter, ANLucBCLuc, constitutes a fusion of small interacting peptides, peptide A and peptide B, with the NLuc and CLuc fragments of luciferase with a caspase-3 cleavage site (DEVD) between pepANLuc (ANLuc) and pepBCLuc (BCLuc). During apoptosis, caspase-3 cleaves the reporter, enabling separation of ANLuc from BCLuc. A high affinity interaction between peptide A and peptide B restores luciferase activity by NLuc and CLuc complementation. Using a D54 glioma model, we demonstrate the reporter’s utility in imaging of apoptosis in living subjects in response to various chemo- and radiation therapy regimens. Results Treatment of live cells and mice carrying D54 tumor xenografts with chemotherapeutic agents such as temozolomide and perifosine resulted in induction of bioluminescence activity, which correlated with activation of caspase-3. Treatment of mice with combination therapy of temozolomide and radiation resulted in increased bioluminescence activity over individual treatments and increased therapeutic response due to enhanced apoptosis. Conclusion The data provided demonstrates the utility of the ANLucBCLuc reporter in dynamic, non-invasive imaging of apoptosis and provides a rationale for use of this technology to optimize dose and schedule of novel therapies or to develop novel combination therapies using existing drugs. PMID:18413842

  4. Non-invasive imaging using reporter genes altering cellular water permeability

    PubMed Central

    Mukherjee, Arnab; Wu, Di; Davis, Hunter C.; Shapiro, Mikhail G.

    2016-01-01

    Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging. PMID:28008959

  5. Iron Oxide-labeled Collagen Scaffolds for Non-invasive MR Imaging in Tissue Engineering

    PubMed Central

    Mertens, Marianne E.; Hermann, Alina; Bühren, Anne; Olde-Damink, Leon; Möckel, Diana; Gremse, Felix; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

    2013-01-01

    Non-invasive imaging holds significant potential for implementation in tissue engineering. It can e.g. be used to monitor the localization and function of tissue-engineered implants, as well as their resorption and remodelling. Thus far, however, the vast majority of efforts in this area of research have focused on the use of ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticle-labeled cells, colonizing the scaffolds, to indirectly image the implant material. Reasoning that directly labeling scaffold materials might be more beneficial (enabling imaging also in case of non-cellularized implants), more informative (enabling the non-invasive visualization and quantification of scaffold degradation) and more easy to translate into the clinic (since cell-free materials are less complex from a regulatory point-of-view), we here prepared three different types of USPIO nanoparticles, and incorporated them both passively and actively (via chemical conjugation; during collagen crosslinking) into collagen-based scaffold materials. We furthermore optimized the amount of USPIO incorporated into the scaffolds, correlated the amount of entrapped USPIO with MR signal intensity, showed that the labeled scaffolds are highly biocompatible, demonstrated that scaffold degradation can be visualized using MRI and provided initial proof-of-principle for the in vivo visualization of the scaffolds. Consequently, USPIO-labeled scaffold materials seem to be highly suitable for image-guided tissue engineering applications. PMID:24569840

  6. Non-invasive measurements of granular flows by magnetic resonance imaging

    SciTech Connect

    Nakagawa, M.; Altobelli, S.A.; Caprihan, A.; Fukushima, E.; Jeong, E.K.

    1993-01-20

    Magnetic Resonance Imaging (MRI) was used to measure granular-flow in a partially filled, steadily rotating, long, horizontal cylinder. This non-invasive technique can yield statistically averaged two-dimensional concentrations and velocity profiles anywhere in the flow of suitable granular materials. First, rigid body motion of a cylinder fill with granular material was studied to confirm the validity of this method. Then, the density variation of the flowing layer where particles collide and dilate, and the depth of the flowing layer and the flow velocity profile were obtained as a function of the cylinder rotation rate.

  7. Detection theory for accurate and non-invasive skin cancer diagnosis using dynamic thermal imaging

    PubMed Central

    Godoy, Sebastián E.; Hayat, Majeed M.; Ramirez, David A.; Myers, Stephen A.; Padilla, R. Steven; Krishna, Sanjay

    2017-01-01

    Skin cancer is the most common cancer in the United States with over 3.5M annual cases. Presently, visual inspection by a dermatologist has good sensitivity (> 90%) but poor specificity (< 10%), especially for melanoma, which leads to a high number of unnecessary biopsies. Here we use dynamic thermal imaging (DTI) to demonstrate a rapid, accurate and non-invasive imaging system for detection of skin cancer. In DTI, the lesion is cooled down and the thermal recovery is recorded using infrared imaging. The thermal recovery curves of the suspected lesions are then utilized in the context of continuous-time detection theory in order to define an optimal statistical decision rule such that the sensitivity of the algorithm is guaranteed to be at a maximum for every prescribed false-alarm probability. The proposed methodology was tested in a pilot study including 140 human subjects demonstrating a sensitivity in excess of 99% for a prescribed specificity in excess of 99% for detection of skin cancer. To the best of our knowledge, this is the highest reported accuracy for any non-invasive skin cancer diagnosis method. PMID:28736673

  8. A servo-mechanical load frame for in situ, non-invasive, imaging of damage development

    SciTech Connect

    Breunig, T.M.; Nichols, M.C.; Gruver, J.S.; Kinney, J.H.; Haupt, D.L.

    1993-12-31

    The X-ray tomographic microscope (XTM) is a non-invasive X-ray imaging instrument for characterizing a material`s structure three-dimensionally with microscopic spatial resolution. The authors have designed a servomechanical load frame for use with the XTM which will allow imaging of samples under load. The load frame is capable of generating tensile or compressive forces up to 15.6 kN with a design system stiffness of 8.76 {times} 10{sup 8} N/m. The test specimen can be rotated through 360{degree}, without induced bending or torque. Torqueless motion is accomplished by synchronously rotating the grips on precision bearings with an accuracy of 0.01{degree}. With this load frame it will be possible, for the first time, to image the initiation and accumulation of internal damage (0.5 {mu}m detectability) formed in a 6 mm diameter specimen during the application of a monotonic or low frequency cyclic load. This is accomplished by interrupting the test and maintaining a fixed load (or displacement) during the non-invasive XTM data collection procedure. This paper describes the in situ load frame design and experimental capabilities. This system can be used to enhance the understanding of failure in composite materials.

  9. Anaphylaxis Imaging: Non-Invasive Measurement of Surface Body Temperature and Physical Activity in Small Animals

    PubMed Central

    Manzano-Szalai, Krisztina; Pali-Schöll, Isabella; Krishnamurthy, Durga; Stremnitzer, Caroline; Flaschberger, Ingo; Jensen-Jarolim, Erika

    2016-01-01

    In highly sensitized patients, the encounter with a specific allergen from food, insect stings or medications may rapidly induce systemic anaphylaxis with potentially lethal symptoms. Countless animal models of anaphylaxis, most often in BALB/c mice, were established to understand the pathophysiology and to prove the safety of different treatments. The most common symptoms during anaphylactic shock are drop of body temperature and reduced physical activity. To refine, improve and objectify the currently applied manual monitoring methods, we developed an imaging method for the automated, non-invasive measurement of the whole-body surface temperature and, at the same time, of the horizontal and vertical movement activity of small animals. We tested the anaphylaxis imaging in three in vivo allergy mouse models for i) milk allergy, ii) peanut allergy and iii) egg allergy. These proof-of-principle experiments suggest that the imaging technology represents a reliable non-invasive method for the objective monitoring of small animals during anaphylaxis over time. We propose that the method will be useful for monitoring diseases associated with both, changes in body temperature and in physical behaviour. PMID:26963393

  10. Quantitative molecular characterization of bovine vitreous and lens with non-invasive dynamic light scattering

    NASA Technical Reports Server (NTRS)

    Ansari, R. R.; Suh, K. I.; Dunker, S.; Kitaya, N.; Sebag, J.

    2001-01-01

    The non-invasive technique of dynamic light scattering (DLS) was used to quantitatively characterize vitreous and lens structure on a molecular level by measuring the sizes of the predominant particles and mapping the three-dimensional topographic distribution of these structural macromolecules in three spatial dimensions. The results of DLS measurements in five fresh adult bovine eyes were compared to DLS measurements in model solutions of hyaluronan (HA) and collagen (Coll). In the bovine eyes DLS measurements were obtained from excised samples of gel and liquid vitreous and compared to the model solutions. Measurements in whole vitreous were obtained at multiple points posterior to the lens to generate a three-dimensional 'map' of molecular structure. The macromolecule distribution in bovine lens was similarly characterized.In each bovine vitreous (Bo Vit) specimen, DLS predominantly detected two distinct particles, which differed in diffusion properties and hence size. Comparisons with model vitreous solutions demonstrated that these most likely corresponded to the Coll and HA components of vitreous. Three-dimensional mapping of Bo Vit found heterogeneity throughout the vitreous body, with different particle size distributions for Coll and HA at different loci. In contrast, the three-dimensional distribution of lens macromolecules was more homogeneous. Thus, the non-invasive DLS technique can quantitate the average sizes of vitreous and lens macromolecules and map their three-dimensional distribution. This method to assess quantitatively the macromolecular structure of vitreous and lens should be useful for clinical as well as experimental applications in health and disease. Copyright 2001 Academic Press.

  11. Quantitative molecular characterization of bovine vitreous and lens with non-invasive dynamic light scattering

    NASA Technical Reports Server (NTRS)

    Ansari, R. R.; Suh, K. I.; Dunker, S.; Kitaya, N.; Sebag, J.

    2001-01-01

    The non-invasive technique of dynamic light scattering (DLS) was used to quantitatively characterize vitreous and lens structure on a molecular level by measuring the sizes of the predominant particles and mapping the three-dimensional topographic distribution of these structural macromolecules in three spatial dimensions. The results of DLS measurements in five fresh adult bovine eyes were compared to DLS measurements in model solutions of hyaluronan (HA) and collagen (Coll). In the bovine eyes DLS measurements were obtained from excised samples of gel and liquid vitreous and compared to the model solutions. Measurements in whole vitreous were obtained at multiple points posterior to the lens to generate a three-dimensional 'map' of molecular structure. The macromolecule distribution in bovine lens was similarly characterized.In each bovine vitreous (Bo Vit) specimen, DLS predominantly detected two distinct particles, which differed in diffusion properties and hence size. Comparisons with model vitreous solutions demonstrated that these most likely corresponded to the Coll and HA components of vitreous. Three-dimensional mapping of Bo Vit found heterogeneity throughout the vitreous body, with different particle size distributions for Coll and HA at different loci. In contrast, the three-dimensional distribution of lens macromolecules was more homogeneous. Thus, the non-invasive DLS technique can quantitate the average sizes of vitreous and lens macromolecules and map their three-dimensional distribution. This method to assess quantitatively the macromolecular structure of vitreous and lens should be useful for clinical as well as experimental applications in health and disease. Copyright 2001 Academic Press.

  12. Non-Invasive In Vivo Imaging of Calcium Signaling in Mice

    PubMed Central

    Rogers, Kelly L.; Picaud, Sandrine; Roncali, Emilie; Boisgard, Raphaël; Colasante, Cesare; Stinnakre, Jacques; Tavitian, Bertrand; Brûlet, Philippe

    2007-01-01

    Rapid and transient elevations of Ca2+ within cellular microdomains play a critical role in the regulation of many signal transduction pathways. Described here is a genetic approach for non-invasive detection of localized Ca2+ concentration ([Ca2+]) rises in live animals using bioluminescence imaging (BLI). Transgenic mice conditionally expressing the Ca2+-sensitive bioluminescent reporter GFP-aequorin targeted to the mitochondrial matrix were studied in several experimental paradigms. Rapid [Ca2+] rises inside the mitochondrial matrix could be readily detected during single-twitch muscle contractions. Whole body patterns of [Ca2+] were monitored in freely moving mice and during epileptic seizures. Furthermore, variations in mitochondrial [Ca2+] correlated to behavioral components of the sleep/wake cycle were observed during prolonged whole body recordings of newborn mice. This non-invasive imaging technique opens new avenues for the analysis of Ca2+ signaling whenever whole body information in freely moving animals is desired, in particular during behavioral and developmental studies. PMID:17912353

  13. Non-invasive imaging of flow and vascular function in disease of the aorta

    PubMed Central

    Whitlock, Matthew C.; Hundley, W. Gregory

    2015-01-01

    With advancements in technology and a better understanding of human cardiovascular physiology, research as well as clinical care can go beyond dimensional anatomy offered by traditional imaging and investigate aortic functional properties and the impact disease has on this function. Linking the knowledge of the histopathological changes with the alterations in aortic function observed on noninvasive imaging results in a better understanding of disease pathophysiology. Translating this to clinical medicine, these noninvasive imaging assessments of aortic function are proving to be able to diagnosis disease, better predict risk, and assess response to therapies. This review is designed to summarize the various hemodynamic measures that can characterize the aorta, the various non-invasive techniques, and applications for various disease states. PMID:26381770

  14. Insights into Parkinson's disease models and neurotoxicity using non-invasive imaging

    SciTech Connect

    Sanchez-Pernaute, Rosario; Jenkins, Bruce G.; Isacson, Ole

    2005-09-01

    Loss of dopamine in the nigrostriatal system causes a severe impairment in motor function in patients with Parkinson's disease and in experimental neurotoxic models of the disease. We have used non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic models of Parkinson's disease. In addition to classic neurotransmitter studies, in these models, it is also possible to characterize associated and perhaps pathogenic factors, such as the contribution of microglia activation and inflammatory responses to neuronal damage. Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders.

  15. Non-invasive detection of murals with pulsed terahertz reflected imaging system

    NASA Astrophysics Data System (ADS)

    Yuan, Minjie; Sun, Wenfeng; Wang, Xinke; Ye, Jiasheng; Wang, Sen; Zhang, Qunxi; Zhang, Yan

    2015-11-01

    Pulsed terahertz reflected imaging technology has been expected to have great potential for the non-invasive analysis of artworks. In this paper, three types of defects hidden in the plaster used to simulate the cases of defects in the murals, have been investigated by a pulsed terahertz reflected imaging system. These preset defects include a circular groove, a cross-shaped slit and a piece of "Y-type" metal plate built in the plaster. With the terahertz reflective tomography, information about defects has been determined involving the thickness from the surface of sample to the built-in defect, the profile and distribution of the defect. Additionally, three-dimensional analyses have been performed in order to reveal the internal structure of defects. Terahertz reflective imaging can be applied to the defect investigation of the murals.

  16. Non-invasive long-term fluorescence live imaging of Tribolium castaneum embryos.

    PubMed

    Strobl, Frederic; Stelzer, Ernst H K

    2014-06-01

    Insect development has contributed significantly to our understanding of metazoan development. However, most information has been obtained by analyzing a single species, the fruit fly Drosophila melanogaster. Embryonic development of the red flour beetle Tribolium castaneum differs fundamentally from that of Drosophila in aspects such as short-germ development, embryonic leg development, extensive extra-embryonic membrane formation and non-involuted head development. Although Tribolium has become the second most important insect model organism, previous live imaging attempts have addressed only specific questions and no long-term live imaging data of Tribolium embryogenesis have been available. By combining light sheet-based fluorescence microscopy with a novel mounting method, we achieved complete, continuous and non-invasive fluorescence live imaging of Tribolium embryogenesis at high spatiotemporal resolution. The embryos survived the 2-day or longer imaging process, developed into adults and produced fertile progeny. Our data document all morphogenetic processes from the rearrangement of the uniform blastoderm to the onset of regular muscular movement in the same embryo and in four orientations, contributing significantly to the understanding of Tribolium development. Furthermore, we created a comprehensive chronological table of Tribolium embryogenesis, integrating most previous work and providing a reference for future studies. Based on our observations, we provide evidence that serosa window closure and serosa opening, although deferred by more than 1 day, are linked. All our long-term imaging datasets are available as a resource for the community. Tribolium is only the second insect species, after Drosophila, for which non-invasive long-term fluorescence live imaging has been achieved.

  17. Non-invasive intravital imaging of cellular differentiation with a bright red-excitable fluorescent protein

    PubMed Central

    Chu, Jun; Haynes, Russell D; Corbel, Stéphane Y; Li, Pengpeng; González-González, Emilio; Burg, John S; Ataie, Niloufar J; Lam, Amy J; Cranfill, Paula J; Baird, Michelle A; Davidson, Michael W; Ng, Ho-Leung; Garcia, K Christopher; Contag, Christopher H; Shen, Kang; Blau, Helen M; Lin, Michael Z

    2014-01-01

    A method for non-invasive visualization of genetically labelled cells in animal disease models with micron-level resolution would greatly facilitate development of cell-based therapies. Imaging of fluorescent proteins (FPs) using red excitation light in the “optical window” above 600 nm is one potential method for visualizing implanted cells. However, previous efforts to engineer FPs with peak excitation beyond 600 nm have resulted in undesirable reductions in brightness. Here we report three new red-excitable monomeric FPs obtained by structure-guided mutagenesis of mNeptune, previously the brightest monomeric FP when excited beyond 600 nm. Two of these, mNeptune2 and mNeptune2.5, demonstrate improved maturation and brighter fluorescence, while the third, mCardinal, has a red-shifted excitation spectrum without reduction in brightness. We show that mCardinal can be used to non-invasively and longitudinally visualize the differentiation of myoblasts and stem cells into myocytes in living mice with high anatomical detail. PMID:24633408

  18. Non-invasive structural and biomechanical imaging of the developing embryos (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhang, Jitao; Wu, Chen; Raghunathan, Raksha; Larin, Kirill V.; Scarcelli, Giuliano

    2017-02-01

    Embryos undergo dramatic changes in size, shape, and mechanical properties during development, which is regulated by both genetic and environmental factors. Quantifying mechanical properties of different embryonic tissues may represent good metrics for the embryonic health and proper development. Alternations and structure coupled with biomechanical information may provide a way for early diagnosis and drug treatment of various congenital diseases. Many methods have been developed to determine the mechanical properties of the embryo, such as atomic force microscopy (AFM), ultrasound elastography (UE), and optical coherent elastography (OCE). However, AFM is invasive and time-consuming. While UE and OCE are both non-invasive methods, the spatial resolutions are limited to mm to sub-mm, which is not enough to observe the details inside the embryo. Brillouin microscopy can potentially enable non-invasive measurement of the mechanical properties of a sample by measuring the spectra of acoustically induced light scattering therein. It has fast speed ( 0.1 second per point) and high resolution (sub-micron), and thus has been widely investigated for biomedical application, such as single cell and tissue. In this work, we utilized this technique to characterize the mechanical property of an embryo. A 2D elasticity imaging of the whole body of an E8 embryo was acquired by a Brillouin microscopy, and the stiffness changes between different organs (such as brain, heart, and spine) were shown. The elasticity maps were correlated with structural information provided by OCT.

  19. Non-invasive imaging of cellulose microfibril orientation within plant cell walls by polarized Raman microspectroscopy.

    PubMed

    Sun, Lan; Singh, Seema; Joo, Michael; Vega-Sanchez, Miguel; Ronald, Pamela; Simmons, Blake A; Adams, Paul; Auer, Manfred

    2016-01-01

    Cellulose microfibrils represent the major scaffold of plant cell walls. Different packing and orientation of the microfibrils at the microscopic scale determines the macroscopic properties of cell walls and thus affect their functions with a profound effect on plant survival. We developed a polarized Raman microspectroscopic method to determine cellulose microfibril orientation within rice plant cell walls. Employing an array of point measurements as well as area imaging and subsequent Matlab-assisted data processing, we were able to characterize the distribution of cellulose microfibril orientation in terms of director angle and anisotropy magnitude. Using this approach we detected differences between wild type rice plants and the rice brittle culm mutant, which shows a more disordered cellulose microfibril arrangement, and differences between different tissues of a wild type rice plant. This novel non-invasive Raman imaging approach allows for quantitative assessment of cellulose fiber orientation in cell walls of herbaceous plants, an important advancement in cell wall characterization.

  20. Patient-specific volume conductor modeling for non-invasive imaging of cardiac electrophysiology.

    PubMed

    Pfeifer, B; Hanser, F; Seger, M; Fischer, G; Modre-Osprian, R; Tilg, B

    2008-01-01

    We propose a general workflow to numerically estimate the spread of electrical excitation in the patients' hearts. To this end, a semi-automatic segmentation pipeline for extracting the volume conductor model of structurally normal hearts is presented. The cardiac electrical source imaging technique aims to provide information about the spread of electrical excitation in order to assist the cardiologist in developing strategies for the treatment of cardiac arrhythmias. The volume conductor models of eight patients were extracted from cine-gated short-axis magnetic resonance imaging (MRI) data. The non-invasive estimation of electrical excitation was compared with the CARTO maps. The development of a volume conductor modeling pipeline for constructing a patient-specific volume conductor model in a fast and accurate way is one essential step to make the technique clinically applicable.

  1. Long Term Non-Invasive Imaging of Embryonic Stem Cells Using Reporter Genes

    PubMed Central

    Sun, Ning; Lee, Andrew; Wu, Joseph C.

    2013-01-01

    Development of non-invasive and accurate methods to track cell fate following delivery will greatly expedite transition of embryonic stem (ES) cell therapy to the clinic. Here we describe a protocol for the in vivo monitoring of stem cell survival, proliferation, and migration using reporter genes. We established stable ES cell lines constitutively expressing double fusion (DF; enhanced green fluorescent protein and firefly luciferase) or triple fusion (TF; monomeric red fluorescent protein, firefly luciferase, and herpes simplex virus thymidine kinase) reporter genes using lentiviral transduction. We used fluorescence activated cell sorting to purify these populations in vitro, bioluminescence imaging and positron emission tomography imaging to track them in vivo, and fluorescence immunostaining to confirm the results ex vivo. Unlike other methods of cell tracking such as iron particle and radionuclide labeling, reporter genes are inherited genetically and can be used to monitor cell proliferation and survival for the lifetime of transplanted cells and their progeny. PMID:19617890

  2. Quantitative non-invasive intracellular imaging of Plasmodium falciparum infected human erythrocytes

    NASA Astrophysics Data System (ADS)

    Edward, Kert; Farahi, Faramarz

    2014-05-01

    Malaria is a virulent pathological condition which results in over a million annual deaths. The parasitic agent Plasmodium falciparum has been extensively studied in connection with this epidemic but much remains unknown about its development inside the red blood cell host. Optical and fluorescence imaging are among the two most common procedures for investigating infected erythrocytes but both require the introduction of exogenous contrast agents. In this letter, we present a procedure for the non-invasive in situ imaging of malaria infected red blood cells. The procedure is based on the utilization of simultaneously acquired quantitative phase and independent topography data to extract intracellular information. Our method allows for the identification of the developmental stages of the parasite and facilitates in situ analysis of the morphological changes associated with the progression of this disease. This information may assist in the development of efficacious treatment therapies for this condition.

  3. Genetic Incorporation of Human Metallothionein into the Adenovirus Protein IX for Non-Invasive SPECT Imaging

    PubMed Central

    Mathis, J. Michael; Bhatia, Shilpa; Khandelwal, Alok; Kovesdi, Imre; Lokitz, Stephen J.; Odaka, Yoshi; Takalkar, Amol M.; Terry, Tracee; Curiel, David T.

    2011-01-01

    As the limits of existing treatments for cancer are recognized, clearly novel therapies must be considered for successful treatment; cancer therapy using adenovirus vectors is a promising strategy. However tracking the biodistribution of adenovirus vectors in vivo is limited to invasive procedures such as biopsies, which are error prone, non-quantitative, and do not give a full representation of the pharmacokinetics involved. Current non-invasive imaging strategies using reporter gene expression have been applied to analyze adenoviral vectors. The major drawback to approaches that tag viruses with reporter genes is that these systems require initial viral infection and subsequent cellular expression of a reporter gene to allow non-invasive imaging. As an alternative to conventional vector detection techniques, we developed a specific genetic labeling system whereby an adenoviral vector incorporates a fusion between capsid protein IX and human metallothionein. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional metallothionein (MT) as a component of their capsid surface. We demonstrate the feasibility of 99mTc binding in vitro to the pIX-MT fusion on the capsid of adenovirus virions using a simple transchelation reaction. SPECT imaging of a mouse after administration of a 99mTc-radiolabeled virus showed clear localization of radioactivity to the liver. This result strongly supports imaging using pIX-MT, visualizing the normal biodistribution of Ad primarily to the liver upon injection into mice. The ability we have developed to view real-time biodistribution in their physiological milieu represents a significant tool to study adenovirus biology in vivo. PMID:21347423

  4. Optimal Non-Invasive Fault Classification Model for Packaged Ceramic Tile Quality Monitoring Using MMW Imaging

    NASA Astrophysics Data System (ADS)

    Agarwal, Smriti; Singh, Dharmendra

    2016-04-01

    Millimeter wave (MMW) frequency has emerged as an efficient tool for different stand-off imaging applications. In this paper, we have dealt with a novel MMW imaging application, i.e., non-invasive packaged goods quality estimation for industrial quality monitoring applications. An active MMW imaging radar operating at 60 GHz has been ingeniously designed for concealed fault estimation. Ceramic tiles covered with commonly used packaging cardboard were used as concealed targets for undercover fault classification. A comparison of computer vision-based state-of-the-art feature extraction techniques, viz, discrete Fourier transform (DFT), wavelet transform (WT), principal component analysis (PCA), gray level co-occurrence texture (GLCM), and histogram of oriented gradient (HOG) has been done with respect to their efficient and differentiable feature vector generation capability for undercover target fault classification. An extensive number of experiments were performed with different ceramic tile fault configurations, viz., vertical crack, horizontal crack, random crack, diagonal crack along with the non-faulty tiles. Further, an independent algorithm validation was done demonstrating classification accuracy: 80, 86.67, 73.33, and 93.33 % for DFT, WT, PCA, GLCM, and HOG feature-based artificial neural network (ANN) classifier models, respectively. Classification results show good capability for HOG feature extraction technique towards non-destructive quality inspection with appreciably low false alarm as compared to other techniques. Thereby, a robust and optimal image feature-based neural network classification model has been proposed for non-invasive, automatic fault monitoring for a financially and commercially competent industrial growth.

  5. MO-E-BRD-01: Is Non-Invasive Image-Guided Breast Brachytherapy Good?

    SciTech Connect

    Hiatt, J.

    2015-06-15

    Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant. A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current

  6. Non-invasive imaging of neuroanatomical structures and neural activation with high-resolution MRI.

    PubMed

    Herberholz, Jens; Mishra, Subrata H; Uma, Divya; Germann, Markus W; Edwards, Donald H; Potter, Kimberlee

    2011-01-01

    Several years ago, manganese-enhanced magnetic resonance imaging (MEMRI) was introduced as a new powerful tool to image active brain areas and to identify neural connections in living, non-human animals. Primarily restricted to studies in rodents and later adapted for bird species, MEMRI has recently been discovered as a useful technique for neuroimaging of invertebrate animals. Using crayfish as a model system, we highlight the advantages of MEMRI over conventional techniques for imaging of small nervous systems. MEMRI can be applied to image invertebrate nervous systems at relatively high spatial resolution, and permits identification of stimulus-evoked neural activation non-invasively. Since the selection of specific imaging parameters is critical for successful in vivo micro-imaging, we present an overview of different experimental conditions that are best suited for invertebrates. We also compare the effects of hardware and software specifications on image quality, and provide detailed descriptions of the steps necessary to prepare animals for successful imaging sessions. Careful consideration of hardware, software, experiments, and specimen preparation will promote a better understanding of this novel technique and facilitate future MEMRI studies in other laboratories.

  7. Non-invasive Detection of Breast Cancer Lymph Node Metastasis using Carbonic Anhydrases IX and XII Targeted Imaging Probes

    PubMed Central

    Tafreshi, Narges K.; Bui, Marilyn M.; Bishop, Kellsey; Lloyd, Mark C.; Enkemann, Steven A.; Lopez, Alexis S.; Abrahams, Dominique; Carter, Bradford W.; Vagner, Josef; Grobmyer, Stephen R.; Gillies, Robert J.; Morse, David L.

    2014-01-01

    Purpose To develop targeted molecular imaging probes for the non-invasive detection of breast cancer lymph node metastasis. Methods Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry (IHC) of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX and CAXII specific monoclonal antibodies (mAbs) to a near-infrared fluorescent dye. Results Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice bearing mammary fat pad tumors of marker expressing cells, and non-expressing cells or by pre-injection of unlabeled antibody. Imaging of LN metastases showed that peritumorally-injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX and CAXII expressing cells into the axillary LNs. Conclusion These imaging probes have potential for non-invasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities. PMID:22016510

  8. Non-Invasive In Vivo Imaging of Tumor-Associated CD133/Prominin

    PubMed Central

    Tsurumi, Chizuko; Esser, Norbert; Firat, Elke; Gaedicke, Simone; Follo, Marie; Behe, Martin; Elsässer-Beile, Ursula; Grosu, Anca-Ligia; Graeser, Ralph; Niedermann, Gabriele

    2010-01-01

    Background Cancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. Hence, the development of methods for non-invasive in vivo detection of cancer stem cells is of great importance. Methodology/Principal Findings Here, we describe successful in vivo detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry. Conclusions/Significance Taken together, our results show that non-invasive antibody-based in vivo imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics. PMID:21187924

  9. A field test study of our non-invasive thermal image analyzer for deceptive detection

    NASA Astrophysics Data System (ADS)

    Sumriddetchkajorn, Sarun; Somboonkaew, Armote; Sodsong, Tawee; Promduang, Itthipol; Sumriddetchkajorn, Niti

    2007-07-01

    We have developed a non-invasive thermal image analyzer for deceptive detection (TAD2) where the far-infrared data around the periorbital and nostril areas are simultaneously analyzed. Measured change in maximum skin temperature around two periorbital regions is converted to a relative blood flow velocity. A respiration pattern is also simultaneously determined via the ratio of the measured maximum and minimum temperatures in the nostril area. In addition, our TAD2 employs a simple normalized cross correlation scheme to independently track locations of the two periorbital and nostril areas. Our field case study from 7 subjects in two real crime scenes and with the use of our baseline classification criteria shows two-fold improvement in classification rate compared to our analysis using either the periorbital or nostril area alone.

  10. Thermal Imaging to Study Stress Non-invasively in Unrestrained Birds

    PubMed Central

    Jerem, Paul; Herborn, Katherine; McCafferty, Dominic; McKeegan, Dorothy; Nager, Ruedi

    2015-01-01

    Stress, a central concept in biology, describes a suite of emergency responses to challenges. Among other responses, stress leads to a change in blood flow that results in a net influx of blood to key organs and an increase in core temperature. This stress-induced hyperthermia is used to assess stress. However, measuring core temperature is invasive. As blood flow is redirected to the core, the periphery of the body can cool. This paper describes a protocol where peripheral body temperature is measured non-invasively in wild blue tits (Cyanistes caeruleus) using infrared thermography. In the field we created a set-up bringing the birds to an ideal position in front of the camera by using a baited box. The camera takes a short thermal video recording of the undisturbed bird before applying a mild stressor (closing the box and therefore capturing the bird), and the bird’s response to being trapped is recorded. The bare skin of the eye-region is the warmest area in the image. This allows an automated extraction of the maximum eye-region temperature from each image frame, followed by further steps of manual data filtering removing the most common sources of errors (motion blur, blinking). This protocol provides a time series of eye-region temperature with a fine temporal resolution that allows us to study the dynamics of the stress response non-invasively. Further work needs to demonstrate the usefulness of the method to assess stress, for instance to investigate whether eye-region temperature response is proportional to the strength of the stressor. If this can be confirmed, it will provide a valuable alternative method of stress assessment in animals and will be useful to a wide range of researchers from ecologists, conservation biologists, physiologists to animal welfare researchers. PMID:26575985

  11. Quantitative, non-invasive imaging of radiation-induced DNA double strand breaks in vivo

    PubMed Central

    Li, Wenrong; Li, Fang; Huang, Qian; Shen, Jingping; Wolf, Frank; He, Yujun; Liu, Xinjian; Hu, Y. Angela; Bedford, Joel. S.; Li, Chuan-Yuan

    2011-01-01

    DNA double strand breaks is a major form of DNA damage and a key mechanism through which radiotherapy and some chemotherapeutic agents kill cancer cells. Despite its importance, measuring DNA double strand breaks is still a tedious task that is normally carried out by gel electrophoresis or immunofluorescence staining. Here we report a novel approach to image and quantify DNA double strand breaks in live mammalian cells through bi-fragment luciferase reconstitution. N- and C- terminal fragments of firefly luciferase gene were fused with H2AX and MDC1 genes, respectively. Our strategy was based on the established fact that at the sites of DNA double strand breaks, H2AX protein is phosphoryated and physically associates with the MDC1 protein, thus bringing together N- and C- luciferase fragments and reconstituting luciferase activity. Our strategy allowed serial, non-invasive quantification of DNA double strand breaks in cells irradiated with x-rays and 56Fe ions. Furthermore, it allowed for the evaluation of DNA double strand breaks (DSBs) non-invasively in vivo in irradiated tumors over two weeks. Surprisingly, we detected a second wave of DSB induction in irradiated tumor cells days after radiation exposure in addition to the initial rapid induction of DSBs. We conclude that our new split-luciferase based method for imaging γ-H2AX-MDC1 interaction is a powerful new tool to study DNA double strand break repair kinetics in vivo with considerable advantage for experiments requiring observations over an extended period of time. PMID:21527553

  12. A novel method for fast imaging of brain function, non-invasively, with light

    NASA Astrophysics Data System (ADS)

    Chance, Britton; Anday, Endla; Nioka, Shoko; Zhou, Shuoming; Hong, Long; Worden, Katherine; Li, C.; Murray, T.; Ovetsky, Y.; Pidikiti, D.; Thomas, R.

    1998-05-01

    Imaging of the human body by any non-invasive technique has been an appropriate goal of physics and medicine, and great success has been obtained with both Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) in brain imaging. Non-imaging responses to functional activation using near infrared spectroscopy of brain (fNIR) obtained in 1993 (Chance, et al. [1]) and in 1994 (Tamura, et al. [2]) are now complemented with images of pre-frontal and parietal stimulation in adults and pre-term neonates in this communication (see also [3]). Prior studies used continuous [4], pulsed [3] or modulated [5] light. The amplitude and phase cancellation of optical patterns as demonstrated for single source detector pairs affords remarkable sensitivity of small object detection in model systems [6]. The methods have now been elaborated with multiple source detector combinations (nine sources, four detectors). Using simple back projection algorithms it is now possible to image sensorimotor and cognitive activation of adult and pre- and full-term neonate human brain function in times < 30 sec and with two dimensional resolutions of < 1 cm in two dimensional displays. The method can be used in evaluation of adult and neonatal cerebral dysfunction in a simple, portable and affordable method that does not require immobilization, as contrasted to MRI and PET.

  13. Using Non-Invasive Multi-Spectral Imaging to Quantitatively Assess Tissue Vasculature

    SciTech Connect

    Vogel, A; Chernomordik, V; Riley, J; Hassan, M; Amyot, F; Dasgeb, B; Demos, S G; Pursley, R; Little, R; Yarchoan, R; Tao, Y; Gandjbakhche, A H

    2007-10-04

    This research describes a non-invasive, non-contact method used to quantitatively analyze the functional characteristics of tissue. Multi-spectral images collected at several near-infrared wavelengths are input into a mathematical optical skin model that considers the contributions from different analytes in the epidermis and dermis skin layers. Through a reconstruction algorithm, we can quantify the percent of blood in a given area of tissue and the fraction of that blood that is oxygenated. Imaging normal tissue confirms previously reported values for the percent of blood in tissue and the percent of blood that is oxygenated in tissue and surrounding vasculature, for the normal state and when ischemia is induced. This methodology has been applied to assess vascular Kaposi's sarcoma lesions and the surrounding tissue before and during experimental therapies. The multi-spectral imaging technique has been combined with laser Doppler imaging to gain additional information. Results indicate that these techniques are able to provide quantitative and functional information about tissue changes during experimental drug therapy and investigate progression of disease before changes are visibly apparent, suggesting a potential for them to be used as complementary imaging techniques to clinical assessment.

  14. Non-Invasive Detection of Lung Inflammation by Near-Infrared Fluorescence Imaging Using Bimodal Liposomes.

    PubMed

    Desu, Hari R; Wood, George C; Thoma, Laura A

    2016-01-01

    Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome results in respiratory obstruction and severe lung inflammation. Critical characteristics of ALI are alveolar edema, infiltration of leukocytes (neutrophils and monocytes), release of pro-inflammatory cytokines and chemokines into broncho-alveolar lavage fluid, and activation of integrin receptors. The purpose of the study was to demonstrate non-invasive detection of lung inflammation using integrin receptor targeted fluorescence liposomes. An inflammation similar to that observed in ALI was elicited in rodents by intra-tracheal instillation of interleukin-1beta (IL-1beta). Cyclic arginine glycine-(D)-aspartic acid-peptide (cRGD-peptide) grafted fluorescence liposomes were administered to ALI induced male Sprague-Dawley rats for targeting lung integrin receptors. Near-infrared fluorescence imaging (NIRFI) was applied for visualization and quantitation of lung inflammation. NIRFI signals were correlated with inflammatory cellular and biochemical markers of lungs. A positive correlation was observed between NIRF signals and lung inflammation markers. Compared to control group, an intense NIRF signal was observed in ALI induced rats in the window 6-24 h post-IL-1beta instillation. Interaction of integrin receptors with targeted liposomes was assumed to contribute to intense NIRF signal. RT-PCR studies showed an elevated lung expression of alphavbeta5 integrin receptors, 12 h post-IL-1beta instillation. In vitro studies demonstrated integrin receptor specificity of targeted liposomes. These targeted liposomes showed binding to alphavbeta5 integrin receptors expressed on alveolar cells. Non-invasive detection of lung inflammation was demonstrated using a combination of integrin receptor targeting and NIRFI.

  15. Non-invasive mechanical properties estimation of embedded objects using tactile imaging sensor

    NASA Astrophysics Data System (ADS)

    Saleheen, Firdous; Oleksyuk, Vira; Sahu, Amrita; Won, Chang-Hee

    2013-05-01

    Non-invasive mechanical property estimation of an embedded object (tumor) can be used in medicine for characterization between malignant and benign lesions. We developed a tactile imaging sensor which is capable of detecting mechanical properties of inclusions. Studies show that stiffness of tumor is a key physiological discerning parameter for malignancy. As our sensor compresses the tumor from the surface, the sensing probe deforms, and the light scatters. This forms the tactile image. Using the features of the image, we can estimate the mechanical properties such as size, depth, and elasticity of the embedded object. To test the performance of the method, a phantom study was performed. Silicone rubber balls were used as embedded objects inside the tissue mimicking substrate made of Polydimethylsiloxane. The average relative errors for size, depth, and elasticity were found to be 67.5%, 48.2%, and 69.1%, respectively. To test the feasibility of the sensor in estimating the elasticity of tumor, a pilot clinical study was performed on twenty breast cancer patients. The estimated elasticity was correlated with the biopsy results. Preliminary results show that the sensitivity of 67% and the specificity of 91.7% for elasticity. Results from the clinical study suggest that the tactile imaging sensor may be used as a tumor malignancy characterization tool.

  16. Molecular classification of non-invasive breast lesions for personalised therapy and chemoprevention

    PubMed Central

    McArt, Darragh; Irwin, Gareth; Harkin, D. Paul; Lioe, Tong; McQuaid, Stephen; James, Jacqueline A.; Maxwell, Perry; Hamilton, Peter; Mullan, Paul B.; Salto-Tellez, Manuel

    2015-01-01

    Breast cancer screening has led to a dramatic increase in the detection of pre-invasive breast lesions. While mastectomy is almost guaranteed to treat the disease, more conservative approaches could be as effective if patients can be stratified based on risk of co-existing or recurrent invasive disease. Here we use a range of biomarkers to interrogate and classify purely non-invasive lesions (PNL) and those with co-existing invasive breast cancer (CEIN). Apart from Ductal Carcinoma in situ (DCIS), relative homogeneity is observed. DCIS contained a greater spread of molecular subtypes. Interestingly, high expression of p-mTOR was observed in all PNL with lower expression in DCIS and invasive carcinoma while the opposite expression pattern was observed for TOP2A. Comparing PNL with CEIN, we have identified p53 and Ki67 as predictors of CEIN with a combined PPV and NPV of 90.48% and 43.3% respectively. Furthermore, HER2 expression showed the best concordance between DCIS and its invasive counterpart. We propose that these biomarkers can be used to improve the management of patients with pre-invasive breast lesions following further validation and clinical trials. p53 and Ki67 could be used to stratify patients into low and high-risk groups for co-existing disease. Knowledge of expression of more actionable targets such as HER2 or TOP2A can be used to design chemoprevention or neo-adjuvant strategies. Increased knowledge of the molecular profile of pre-invasive lesions can only serve to enhance our understanding of the disease and, in the era of personalised medicine, bring us closer to improving breast cancer care. PMID:26657114

  17. Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia.

    PubMed

    Jordan, Lori C; Gindville, Melissa C; Scott, Allison O; Juttukonda, Meher R; Strother, Megan K; Kassim, Adetola A; Chen, Sheau-Chiann; Lu, Hanzhang; Pruthi, Sumit; Shyr, Yu; Donahue, Manus J

    2016-03-01

    Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the

  18. Multifunctional single beam acoustic tweezer for non-invasive cell/organism manipulation and tissue imaging

    PubMed Central

    Lam, Kwok Ho; Li, Ying; Li, Yang; Lim, Hae Gyun; Zhou, Qifa; Shung, Koping Kirk

    2016-01-01

    Non-contact precise manipulation of single microparticles, cells, and organisms has attracted considerable interest in biophysics and biomedical engineering. Similar to optical tweezers, acoustic tweezers have been proposed to be capable of manipulating microparticles and even cells. Although there have been concerted efforts to develop tools for non-contact manipulation, no alternative to complex, unifunctional tweezer has yet been found. Here we report a simple, low-cost, multifunctional single beam acoustic tweezer (SBAT) that is capable of manipulating an individual micrometer scale non-spherical cell at Rayleigh regime and even a single millimeter scale organism at Mie regime, and imaging tissue as well. We experimentally demonstrate that the SBAT with an ultralow f-number (f# = focal length/aperture size) could manipulate an individual red blood cell and a single 1.6 mm-diameter fertilized Zebrafish egg, respectively. Besides, in vitro rat aorta images were collected successfully at dynamic foci in which the lumen and the outer surface of the aorta could be clearly seen. With the ultralow f-number, the SBAT offers the combination of large acoustic radiation force and narrow beam width, leading to strong trapping and high-resolution imaging capabilities. These attributes enable the feasibility of using a single acoustic device to perform non-invasive multi-functions simultaneously for biomedical and biophysical applications. PMID:27874052

  19. Peripheral arterial disease: the evolving role of non-invasive imaging.

    PubMed

    Owen, A R; Roditi, G H

    2011-03-01

    Peripheral arterial disease is usually secondary to stenotic or occlusive atherosclerosis and is both common and increasing in western society. The majority of symptomatic patients have intermittent claudication and only a minority (<2% and typically those with diabetes mellitus or renal failure) progress to critical limb ischaemia, heralded by the onset of rest pain and/or tissue loss. Imaging is largely reserved for patients with disabling symptoms in whom revascularisation is planned. In these patients, accurate depiction of the vascular anatomy is critical for clinical decision making as the distribution and severity of disease are key factors determining whether revascularisation should be by endovascular techniques or open surgery. Driven by advances in technology, non-invasive vascular imaging has recently undergone significant refinement and has replaced conventional digital subtraction angiography for many clinical indications. In this review, the relative merits and limitations of duplex ultrasound, CT angiography, and magnetic resonance angiography are discussed, emerging imaging techniques are described, and complications relating to the use of intravascular contrast agents are highlighted.

  20. Multifunctional single beam acoustic tweezer for non-invasive cell/organism manipulation and tissue imaging

    NASA Astrophysics Data System (ADS)

    Lam, Kwok Ho; Li, Ying; Li, Yang; Lim, Hae Gyun; Zhou, Qifa; Shung, Koping Kirk

    2016-11-01

    Non-contact precise manipulation of single microparticles, cells, and organisms has attracted considerable interest in biophysics and biomedical engineering. Similar to optical tweezers, acoustic tweezers have been proposed to be capable of manipulating microparticles and even cells. Although there have been concerted efforts to develop tools for non-contact manipulation, no alternative to complex, unifunctional tweezer has yet been found. Here we report a simple, low-cost, multifunctional single beam acoustic tweezer (SBAT) that is capable of manipulating an individual micrometer scale non-spherical cell at Rayleigh regime and even a single millimeter scale organism at Mie regime, and imaging tissue as well. We experimentally demonstrate that the SBAT with an ultralow f-number (f# = focal length/aperture size) could manipulate an individual red blood cell and a single 1.6 mm-diameter fertilized Zebrafish egg, respectively. Besides, in vitro rat aorta images were collected successfully at dynamic foci in which the lumen and the outer surface of the aorta could be clearly seen. With the ultralow f-number, the SBAT offers the combination of large acoustic radiation force and narrow beam width, leading to strong trapping and high-resolution imaging capabilities. These attributes enable the feasibility of using a single acoustic device to perform non-invasive multi-functions simultaneously for biomedical and biophysical applications.

  1. Non-invasive Measurement of Renal Blood Flow by Magnetic Resonance Imaging (MRI) in Rats.

    PubMed

    Romero, Cesar A; Cabral, Glauber; Knight, Robert A; Ding, Guangliang; Peterson, Edward L; Carretero, Oscar A

    2017-10-04

    Renal blood flow (RBF) provides important information regarding renal physiology and nephropathies. Arterial spin labeling-magnetic resonance imaging (ASL-MRI) is a non-invasive method of measuring blood flow without exogenous contrast media. However, low signal/noise ratio and respiratory motion artifacts are challenges for RBF measurements in small animals. Our objective was to evaluate the feasibility and reproducibility of RBF measures by ASL-MRI using respiratory-gating and navigator correction methods to reduce motion artifacts. ASL-MRI images were obtained from the kidneys of Sprague-Dawley (SD) rats on a 7 tesla Varian MRI system with a spin-echo imaging sequence. After 4 days, the study was repeated to evaluate its reproducibility. RBF was also measured in animals under unilateral nephrectomy and in renal artery stenosis (RST) to evaluate the sensitivity in high and low RBF models, respectively. RBF was also evaluated in Dahl salt-sensitive (SS) rats and spontaneous hypertensive rats (SHR). In SD rats the cortical RBFs (cRBF) were 305±59 and 271.8±39 ml/min/100 g tissue in the right and left kidneys, respectively. Re-test analysis revealed no differences (p=0.2). The test-retest reliability coefficient was 92±5%. The cRBFs before and after the nephrectomy were 296.8±30 and 428.2±45 ml/min/100 g (p=0.02), respectively. The kidneys with RST exhibited a cRBF decrease compared with sham animals (86±17.6 vs. 198±33.7 ml/min/100 g tissue; p<0.01). The cRBFs in SD, Dahl-ss and SHR rats were not different (p=0.35). We conclude that ASL-MRI performed with navigator correction and respiratory gating is a feasible and reliable non-invasive method for measuring RBF in rats. Copyright © 2017, American Journal of Physiology-Renal Physiology.

  2. Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy.

    PubMed

    Hynynen, Kullervo; Jones, Ryan M

    2016-09-07

    Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

  3. Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy

    NASA Astrophysics Data System (ADS)

    Hynynen, Kullervo; Jones, Ryan M.

    2016-09-01

    Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

  4. A method for non-invasive full-field imaging and quantification of chemical species.

    PubMed

    Shkolnikov, Viktor; Santiago, Juan G

    2013-04-21

    We present a novel method for full-field scalar visualization and quantification of species concentration fields. We term this method species-altered fluorescence imaging (SAFI). The method employs electrically neutral fluorescent dyes whose quantum yields are selectively quenched or enhanced by species of interest. SAFI enables simultaneous imaging of material interfaces and provides non-invasive, scalar-field quantitation of two-dimensional species concentration fields. We describe criteria for choosing SAFI dyes and tabulate 35 promising SAFI dyes and their relevant properties. Next, we describe species concentration quantification with SAFI via Stern-Volmer quenching and discuss the sensitivity and resolution of our method. We demonstrate this method with two dyes, 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ) and 10-(3-sulfopropyl)acridinium betaine (SAB). We demonstrate our method in full-field visualization of several challenging electrokinetic flows: isotachophoresis (ITP) in both cationic and anionic modes, and in a convective electrokinetic instability (EKI) flow. Through these experiments we collectively quantify ion concentration shock velocities, simultaneously measure concentrations of five species, and quantify the development of an unsteady, chaotic, 2D flow.

  5. Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy

    PubMed Central

    Hynynen, Kullervo; Jones, Ryan M.

    2016-01-01

    Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy. PMID:27494561

  6. Development of an X-ray Computed Tomography System for Non-Invasive Imaging of Industrial Materials

    SciTech Connect

    Abdullah, J.; Sipaun, S. M.; Mustapha, I.; Zain, R. M.; Rahman, M. F. A.; Mustapha, M.; Shaari, M. R.; Hassan, H.; Said, M. K. M.; Mohamad, G. H. P.; Ibrahim, M. M.

    2008-05-20

    X-ray computed tomography is a powerful non-invasive imaging technique for viewing an object's inner structures in two-dimensional cross-section images without the need to physically section it. The invention of CT techniques revolutionised the field of medical diagnostic imaging because it provided more detailed and useful information than any previous non-invasive imaging techniques. The method is increasingly being used in industry, aerospace, geosciences and archaeology. This paper describes the development of an X-ray computed tomography system for imaging of industrial materials. The theoretical aspects of CT scanner, the system configurations and the adopted algorithm for image reconstruction are discussed. The penetrating rays from a 160 kV industrial X-ray machine were used to investigate structures that manifest in a manufactured component or product. Some results were presented in this paper.

  7. Analysis of progenitor cell-scaffold combinations by in vivo non-invasive photonic imaging.

    PubMed

    Román, Irene; Vilalta, Marta; Rodriguez, Julio; Matthies, Annette M; Srouji, Samer; Livne, Erella; Hubbell, Jeffrey A; Rubio, Nuria; Blanco, Jerónimo

    2007-06-01

    Recent developments in stem cell research have promoted a flourishing of new biomaterials and scaffolds for tissue repair. However, there is a scarcity of procedures to monitor the performance of scaffold-stem cell combinations implanted in live animals, avoiding the inherent artefacts associated with in vitro assay conditions. We report the implementation of a procedure based on the use of the luciferase gene as a cell proliferation tracer to monitor, by in vivo non-invasive imaging, the performance of stem cell-biomaterial combinations used for tissue regeneration. In a model system using immunodepressed mice we show preference of a mouse embryonic mesenchymal cell line (C3H/10T1/2) for specific implantation sites and biomaterials during a prolonged in vivo growth period (3 months). Moreover, we analyzed the safety of implanted cells using a sensitive luminometric procedure and showed that the implanted cells did not spread to other organs. Our results demonstrate the utility of this simple and resource-saving procedure in the development and screening of biomaterials for tissue engineering.

  8. Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity

    SciTech Connect

    Ho, Gideon; Zhang Chunyan; Zhuo Lang . E-mail: lzhuo@ibn.a-star.edu.sg

    2007-05-15

    Gliosis is a universal response of Brain to almost all types of neural insults, including neurotoxicity, neurodegeneration, viral infection, and stroke. A hallmark of gliotic reaction is the up-regulation of the astrocytic biomarker GFAP (glial fibrillary acidic protein), which often precedes the anatomically apparent damages in Brain. In this study, neonatal transgenic mice at postnatal day (PD) 4 expressing GFP (green fluorescent protein) under the control of a widely used 2.2-kb human GFAP promoter in Brain are treated with two model neurotoxicants, 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH{sub 3}-MPTP), and kainic acid (KA), respectively, to induce gliosis. Here we show that the neurotoxicant-induced acute gliosis can be non-invasively imaged and quantified in Brain of conscious (un-anesthetized) mice in real-time, at 0, 2, 4, 6, and 8 h post-toxicant dosing. Therefore the current methodology could be a useful tool for studying the developmental aspects of neuropathies and neurotoxicity.

  9. Imaging iron in skin and liver: Non-invasive tools for hemochromatosis therapy

    NASA Astrophysics Data System (ADS)

    Pinheiro, T.; Fleming, R.; Gonçalves, A.; Neres, M.; Alves, L. C.; Silva, J. N.; Filipe, P.; Silva, R.

    2009-06-01

    Hemochromatosis is a hereditary disease that causes an inappropriate intestinal absorption of Fe resulting in its accumulation in multiple organs, such as liver, heart and skin. Fe metabolism indicators in the circulation do not provide reliable indication of organ overload as they can be influenced by other clinical conditions. Assessing metabolism organs such as liver requires invasive procedures which is not adequate to patient's serial observations. Our aim was establishing cross sectional and longitudinal information on the amount of Fe that deposited in skin and liver during a life period, how iron is cleared out by therapy intervention and study the relationship of these changes between the two organs using non-invasive methods. Results on skin Fe deposition were evaluated by nuclear microscopy techniques and liver Fe concentrations determined by quantitative magnetic resonance imaging. Skin and liver Fe concentrations were correlated. Though Fe deposits in the two organs were differently associated with blood Fe metabolism conventional markers. Fe serial variations in skin and liver highlighted the value of assessing Fe organ deposits for estimating hemochromatosis evolution and therapy efficacy.

  10. Combined Neutron and X-ray Imaging for Non-invasive Investigations of Cultural Heritage Objects

    NASA Astrophysics Data System (ADS)

    Mannes, D.; Schmid, F.; Frey, J.; Schmidt-Ott, K.; Lehmann, E.

    The combined utilization of neutron and X-ray imaging for non-invasive investigations of cultural heritage objects is demonstrated on the example of a short sword found a few years ago in lake Zug, Switzerland. After conservation treatments carried out at the Swiss National Museum the sword was examined at the Paul Scherrer Institut (PSI), Villigen (CH), by means of neutron and X-ray computer tomography (CT). The two types of radiation show different interaction behavior with matter, which makes the two methods complementary. While X-rays show a strong correlation of the attenuation with the atomic number, neutrons demonstrate a high sensitivity for some light elements, such as Hydrogen and thus organic material, while some heavy elements (such as Lead) show high penetrability. The examined object is a composite of metal and organic material, which makes it an ideal example to show the complementarity of the two methods as it features materials, which are rather transparent for one type of radiation, while yielding at the same time high contrast for the other. Only the combination of the two methods made an exhaustive examination of the object possible and allowed to rebuild an accurate replica of the sword.

  11. Non-invasive imaging of transgenic GFP expression in neonatal mouse brain

    NASA Astrophysics Data System (ADS)

    Ho, Gideon; Zhang, Chunyan; Zhuo, Lang

    2007-02-01

    Glial fibrillary acidic protein (GFAP) is a traditional biomarker for astrocytes of the central nervous system. In this study, non-invasive in vivo imaging of GFAP-GFP (green fluorescent protein) expression in the brain of neonatal transgenic mice is used as a novel method to investigate the relationship between the expression of the transgene at 0, 2, 4, 6 and 8 hr post-treatment in mice subjected to a single administration of 12 mg/kg of neurotoxin 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH 3-MPTP). The GFP elevation was found to peak at 6 hr and lasted to at least 8 hr after the toxin treatment. Histological examination of fixed brain sections using immunohistochemistry (IHC) shows an increase in GFP and GFAP signal from the substantia nigra pars compacta (SNpc) and the hippocampus. The results have provided quantitative fluorescence and qualitative histological evidence for the activation of the GFAP-GFP transgene in astrocytes following neurotoxin 2'-CH 3-MPTP administration, suggesting that the model described here could be used to study neuronal degeneration such as Parkinson's disease and in general, developmental neurotoxicity in live animals.

  12. Non-invasive single-cell biomechanical analysis using live-imaging datasets.

    PubMed

    Pearson, Yanthe E; Lund, Amanda W; Lin, Alex W H; Ng, Chee P; Alsuwaidi, Aysha; Azzeh, Sara; Gater, Deborah L; Teo, Jeremy C M

    2016-09-01

    The physiological state of a cell is governed by a multitude of processes and can be described by a combination of mechanical, spatial and temporal properties. Quantifying cell dynamics at multiple scales is essential for comprehensive studies of cellular function, and remains a challenge for traditional end-point assays. We introduce an efficient, non-invasive computational tool that takes time-lapse images as input to automatically detect, segment and analyze unlabeled live cells; the program then outputs kinematic cellular shape and migration parameters, while simultaneously measuring cellular stiffness and viscosity. We demonstrate the capabilities of the program by testing it on human mesenchymal stem cells (huMSCs) induced to differentiate towards the osteoblastic (huOB) lineage, and T-lymphocyte cells (T cells) of naïve and stimulated phenotypes. The program detected relative cellular stiffness differences in huMSCs and huOBs that were comparable to those obtained with studies that utilize atomic force microscopy; it further distinguished naïve from stimulated T cells, based on characteristics necessary to invoke an immune response. In summary, we introduce an integrated tool to decipher spatiotemporal and intracellular dynamics of cells, providing a new and alternative approach for cell characterization. © 2016. Published by The Company of Biologists Ltd.

  13. Magnetocardiography provides non-invasive three-dimensional electroanatomical imaging of cardiac electrophysiology.

    PubMed

    Fenici, Riccardo; Brisinda, Donatella

    2007-07-01

    More than two decades of research work have shown that magnetocardiographic mapping (MCG) is reliable for non-invasive three-dimensional electroanatomical imaging (3D-EAI) of arrhythmogenic substrates. Magnetocardiographic mapping is now become appealing to interventional electrophysiologists after recent evidence that MCG-based dynamic imaging of atrial arrhythmias could be useful to classify patients with atrial fibrillation (AF) before ablation and to plan the most appropriate therapeutic approach. This article will review some key-points of 3D-EAI and discuss what is still missing to favor clinical applicability of MCG-based 3D-EAI. Magnetocardiographic mapping is performed with a 36-channel unshielded mapping system, based on DC-SQUID sensors coupled to second-order axial gradiometers (pick-up coil 19 mm and 55-70 mm baselines; sensitivity of 20 fT/Sqrt[Hz] in above 1 Hz), as part of the electrophysiologic investigation protocol, tailored to the diagnostic need of each arrhythmic patient. More than 500 arrhythmic patients have been investigated so far. The MCG-based 3D-EAI has proven useful to localize well-confined arrhythmogenic substrates, such as focal ventricular tachycardia or preexcitation, to understand some causes for ablation failure, to study atrial electrophysiology including spectral analysis and localization of dominant frequency components of AF. However, MCG is still missing software tools for automatic and/or interactive 3D imaging, and multimodal data fusion equivalent to those provided with systems for invasive 3D electroanatomical mapping. Since there is an increasing trend to favor interventional treatment of arrhythmias, clinical application of MCG 3D-EAI is foreseen to improve preoperative selection of patients, to plan the appropriate interventional approach and to reduce ablation failure.

  14. The impact of new trends in POCTs for companion diagnostics, non-invasive testing and molecular diagnostics.

    PubMed

    Huckle, David

    2015-06-01

    Point-of-care diagnostics have been slowly developing over several decades and have taken on a new importance in current healthcare delivery for both diagnostics and development of new drugs. Molecular diagnostics have become a key driver of technology change and opened up new areas in companion diagnostics for use alongside pharmaceuticals and in new clinical approaches such as non-invasive testing. Future areas involving smartphone and other information technology advances, together with new developments in molecular biology, microfluidics and surface chemistry are adding to advances in the market. The focus for point-of-care tests with molecular diagnostic technologies is focused on advancing effective applications.

  15. Non-invasive imaging of breast cancer: synthesis and study of novel near-infrared fluorescent estrogen conjugate

    NASA Astrophysics Data System (ADS)

    Jose, Iven; Vishnoi, Gargi; Deodhar, Kodand; Desai, Uday

    2005-04-01

    The use of near-infrared (NIR) spectroscopy to interrogate deeper tissue volume has shown enormous potential for molecular-based non-invasive imaging when coupled with appropriate excitable dyes. As most of the breast cancers are hormone dependent hence determination of the hormonal receptor status gains paramount importance when deciding the treatment regime for the patient. Since proliferations of the breast cancer cells are often driven by estrogen, we focus on to developing a technique to detect estrogen receptor status. As a first step, the objective of this work was to synthesize and characterize one such novel NIR fluorescent (NIRF) conjugate, which could potentially be used to detect estrogen receptors. The conjugate was synthesized by ester formation between 17-b estradiol and a cyanine dye namely: bis-1, 1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. The cyanine dye is a hydrophilic derivative of indocyanine green (ICG). 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. This cyanine dye has a partition coefficient less than 0.005 as compared to that of ICG (>200)[1]. In addition the ester showed enhanced fluorescent quantum yield than ICG. 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 developed was tested on the breast cancer cell lines MCF-7 and found non-toxic. The tagging characteristics were pivotal determinants underlying the ability of the fluorescent conjugate in binding the estrogen receptor of the breast cancer cells. This technique offers the potential of non-invasive detection of hormone receptor status in vivo and may help in decreasing the load of unnecessary biopsies

  16. Species and sex identification of the Korean goral (Nemorhaedus caudatus) by molecular analysis of non-invasive samples.

    PubMed

    Kim, Baek Jun; Lee, Yun-Sun; An, Jung-hwa; Park, Han-Chan; Okumura, Hideo; Lee, Hang; Min, Mi-Sook

    2008-09-30

    Korean long-tailed goral (Nemorhaedus caudatus) is one of the most endangered species in South Korea. However, detailed species distribution and sex ratio data on the elusive goral are still lacking due to difficulty of identification of the species and sex in the field. The primary aim of this study was to develop an economical PCR-RFLP method to identify species using invasive or non-invasive samples from five Korean ungulates: goral (N. caudatus), roe deer (Capreolus pygargus), feral goat (Capra hircus), water deer (Hydropotes inermis) and musk deer (Moschus moschiferus). The secondary aim was to find more efficient molecular sexing techniques that may be applied to invasive or non-invasive samples of ungulate species. We successfully utilized PCR-RFLP of partial mitochondrial cytochrome b gene (376 bp) for species identification, and sex-specific amplification of ZFX/Y and AMELX/Y genes for sexing. Three species (goral, goat and water deer) showed distinctive band patterns by using three restriction enzymes (XbaI, StuI or SspI). Three different sexing primer sets (LGL331/335 for ZFX/Y gene; SE47/48 or SE47/53 for AMELX/Y gene) produced sex-specific band patterns in goral, goat and roe deer. Our results suggest that the molecular analyses of non-invasive samples might provide us with potential tools for the further genetic and ecological study of Korean goral and related species.

  17. Multiparametric Functional MRI: Non-Invasive Imaging of Inflammation and Edema Formation after Kidney Transplantation in Mice

    PubMed Central

    Gutberlet, Marcel; Bräsen, Jan Hinrich; Jang, Mi-Sun; Thorenz, Anja; Chen, Rongjun; Hertel, Barbara; Barrmeyer, Amelie; Schmidbauer, Martina; Meier, Martin; von Vietinghoff, Sibylle; Khalifa, Abedalrazag; Hartung, Dagmar; Haller, Hermann; Wacker, Frank

    2016-01-01

    Background Kidney transplantation (ktx) in mice is used to learn about rejection and to develop new treatment strategies. Past studies have mainly been based on histological or molecular biological methods. Imaging techniques to monitor allograft pathology have rarely been used. Methods Here we investigated mice after isogenic and allogenic ktx over time with functional MRI with diffusion-weighted imaging (DWI) and mapping of T2-relaxation time (T2-mapping) to assess graft inflammation and edema formation. To characterize graft pathology, we used PAS-staining, counted CD3-positive T-lymphocytes, analyzed leukocytes by means flow cytometry. Results DWI revealed progressive restriction of diffusion of water molecules in allogenic kidney grafts. This was paralleled by enhanced infiltration of the kidney by inflammatory cells. Changes in tissue diffusion were not seen following isogenic ktx. T2-times in renal cortex were increased after both isogenic and allogenic transplantation, consistent with tissue edema due to ischemic injury following prolonged cold ischemia time of 60 minutes. Lack of T2 increase in the inner stripe of the inner medulla in allogenic kidney grafts matched loss of tubular autofluorescence and may result from rejection-driven reductions in tubular water content due to tubular dysfunction and renal functional impairment. Conclusions Functional MRI is a valuable non-invasive technique for monitoring inflammation, tissue edema and tubular function. It permits on to differentiate between acute rejection and ischemic renal injury in a mouse model of ktx. PMID:27632553

  18. Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognitive Functions

    DTIC Science & Technology

    2017-05-14

    AFRL-AFOSR-JP-TR-2017-0052 Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions...Pravat Mandal National Brain Research Centre Final Report 05/14/2017 DISTRIBUTION A: Distribution approved for public release. AF Office Of Scientific...invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions 5a.  CONTRACT NUMBER 5b.  GRANT

  19. Apoptosis imaging for monitoring DR5 antibody accumulation and pharmacodynamics in brain tumors non-invasively

    PubMed Central

    Weber, Thomas G.; Osl, Franz; Renner, Anja; Pöschinger, Thomas; Galbán, Stefanie; Rehemtulla, Alnawaz; Scheuer, Werner

    2014-01-01

    High grade gliomas often possess an impaired blood-brain barrier (BBB) which allows delivery of large molecules to brain tumors. However, achieving optimal drug concentrations in brain tumors remains a significant hurdle for treating patients successfully. Thus, detailed investigations of drug activities in gliomas are needed. To investigate BBB penetration, pharmacodynamics and tumor retention kinetics, we studied an agonistic DR5 antibody in a brain tumor xenograft model to investigate a non-invasive imaging method for longitudinal monitoring of apoptosis induction by this antibody. Brain tumors were induced by intracranial (i.c.) implantation of a luciferase-expressing tumor cell line as a reporter. To quantify accumulation of anti-DR5 in brain tumors, we generated a dose response curve for apoptosis induction after i.c. delivery of fluorescence-labeled anti-DR5 at different dosages. Assuming 100% drug delivery after i.c. application, the amount of accumulated antibody after i.v. application was calculated relative to its apoptosis induction. We found that up to 0.20–0.97% of antibody delivered i.v. reached the brain tumor, but that apoptosis induction declined quickly within 24 hours. These results were confirmed by 3D fluorescence microscopy of antibody accumulation in explanted brains. Nonetheless, significant antitumor efficacy was documented after anti-DR5 delivery. We further demonstrated that antibody crossing the BBB was facilitated its impairment in brain tumors. These imaging methods enable the quantification of antibody accumulation and pharmacodynamics in brain tumors, offering a holistic approach for assessment of CNS targeting drugs. PMID:24509903

  20. Future Imaging Alternatives: The Clinical Non-invasive Modalities in Diagnosis of Oral Squamous Cell Carcinoma (OSCC)

    PubMed Central

    Omar, Esam

    2015-01-01

    Background : Oral squamous cell carcinoma (OSCC) has a remarkably high incidence worldwide, and a fairly serious prognosis. This is encouraging further research into advanced technologies for non-invasive methods of making early diagnoses, ideally in primary care settings. Method : In this article, the available objective Non-imaging methods for diagnosing OSCC have been reviewed. MEDLINE, EMBASE, the Cochrane Library, and CINAHL have been searched for advanced technologies of non-invasive methods in diagnosis of OSCC, including oral brush biopsy, optical biopsy, saliva-based oral cancer diagnosis and others. Results : Toluidine blue, one of the oldest non-invasive methods for diagnosing OSCC, is unreliable because of its subjectivity, as it is dependent on the experience of the examiner. The diagnosis of Oral carcinoma by Oral brush biopsy with exfoliative cytology based on nano-bio-chip sensor platform shows 97–100% sensitivity and 86% specificity. Another promising non-invasive technique for OSCC diagnosis is saliva-based oral cancer diagnosis, which is an alternative to serum testing. Optical biopsy, which uses the technology of spectroscopy, can be used to detect changes at a sub-cellular level; thus, it provides information that may not be available with conventional histology with reliable sensitivity and specificity. Conclusion : It is clearly evident that screening and early effective detection of cancer and pre-cancerous lesions have the potential to reduce the morbidity and mortality of this disease. The imaging technologies are subjective procedures since all of them require interpretation and significantly affected by the examiner experience. These make further research for advanced objective procedures. Saliva-based oral cancer diagnosis and optical biopsy are promising objective non-invasive methods for diagnosing OSCC. They are easy to perform clinically at primary care set. They show promising pathways for future development of more effective

  1. Non-invasive and non-destructive characterization of tissue engineered constructs using ultrasound imaging technologies: a review

    PubMed Central

    Kim, Kang; Wagner, William R.

    2015-01-01

    With the rapid expansion of biomaterial development and coupled efforts to translate such advances toward the clinic, non-invasive and non-destructive imaging tools to evaluate implants in situ in a timely manner are critically needed. The required multilevel information is comprehensive, including structural, mechanical, and biological changes such as scaffold degradation, mechanical strength, cell infiltration, extracellular matrix formation and vascularization to name a few. With its inherent advantages of non-invasiveness and non-destructiveness, ultrasound imaging can be an ideal tool for both preclinical and clinical uses. In this review, currently available ultrasound imaging technologies that have been applied in vitro and in vivo for tissue engineering and regenerative medicine are discussed and some new emerging ultrasound technologies and multi-modality approaches utilizing ultrasound are introduced. PMID:26518412

  2. Non-invasive and Non-destructive Characterization of Tissue Engineered Constructs Using Ultrasound Imaging Technologies: A Review.

    PubMed

    Kim, Kang; Wagner, William R

    2016-03-01

    With the rapid expansion of biomaterial development and coupled efforts to translate such advances toward the clinic, non-invasive and non-destructive imaging tools to evaluate implants in situ in a timely manner are critically needed. The required multi-level information is comprehensive, including structural, mechanical, and biological changes such as scaffold degradation, mechanical strength, cell infiltration, extracellular matrix formation and vascularization to name a few. With its inherent advantages of non-invasiveness and non-destructiveness, ultrasound imaging can be an ideal tool for both preclinical and clinical uses. In this review, currently available ultrasound imaging technologies that have been applied in vitro and in vivo for tissue engineering and regenerative medicine are discussed and some new emerging ultrasound technologies and multi-modality approaches utilizing ultrasound are introduced.

  3. Imaging the Efficacy of Anti-Inflammatory Liposomes in a Rabbit Model of Atherosclerosis by Non-Invasive Imaging

    PubMed Central

    Lobatto, Mark E.; Calcagno, Claudia; Metselaar, Josbert M.; Storm, Gert; Stroes, Erik S. G.; Fayad, Zahi A.; Mulder, Willem J. M.

    2013-01-01

    Nanomedicine can provide a potent alternative to current therapeutic strategies for atherosclerosis. For example, the encapsulation of anti-inflammatory drugs into liposomes improves their pharmacokinetics and biodistribution, thereby enhancing bioavailability to atherosclerotic plaques and improving therapeutic efficacy. The evaluation of this type of experimental therapeutics can greatly benefit from in vivo evaluation to assess biological changes, which can be performed by non-invasive imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Here, we will illustrate the methods for inducing atherosclerosis in a rabbit model, the production of anti-inflammatory liposomes and monitoring of therapeutic efficacy of experimental therapeutics with the above-mentioned imaging techniques. PMID:22449928

  4. Imaging the efficacy of anti-inflammatory liposomes in a rabbit model of atherosclerosis by non-invasive imaging.

    PubMed

    Lobatto, Mark E; Calcagno, Claudia; Metselaar, Josbert M; Storm, Gert; Stroes, Erik S G; Fayad, Zahi A; Mulder, Willem J M

    2012-01-01

    Nanomedicine can provide a potent alternative to current therapeutic strategies for atherosclerosis. For example, the encapsulation of anti-inflammatory drugs into liposomes improves their pharmacokinetics and biodistribution, thereby enhancing bioavailability to atherosclerotic plaques and improving therapeutic efficacy. The evaluation of this type of experimental therapeutics can greatly benefit from in vivo evaluation to assess biological changes, which can be performed by non-invasive imaging techniques, such as ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Here, we will illustrate the methods for inducing atherosclerosis in a rabbit model, the production of anti-inflammatory liposomes and monitoring of therapeutic efficacy of experimental therapeutics with the above-mentioned imaging techniques.

  5. Improved Geologic Interpretation of Non-invasive Electrical Resistivity Imaging from In-situ Samples

    NASA Astrophysics Data System (ADS)

    Mucelli, A.; Aborn, L.; Jacob, R.; Malusis, M.; Evans, J.

    2016-12-01

    Non-invasive geophysical techniques are useful in characterizing the subsurface geology without disturbing the environment, however, the ability to interpret the subsurface is enhanced by invasive work. Since geologic materials have electrical resistivity values it allows for a geologic interpretation to be made based on variations of electrical resistivity measured by electrical resistivity imaging (ERI). This study focuses on the pre-characterization of the geologic subsurface from ERI collected adjacent to the Montandon Marsh, a wetland located near Lewisburg, PA within the West Branch of the Susquehanna River watershed. The previous invasive data, boreholes, indicate that the subsurface consists of limestone and shale bedrock overlain with sand and gravel deposits from glacial outwash and aeolian processes. The objective is to improve our understanding of the subsurface at this long-term hydrologic research site by using excavation results, specifically observed variations in geologic materials and electrical resistivity laboratory testing of subsurface samples. The pre-excavation ERI indicated that the shallow-most geologic material had a resistivity value of 100-500 ohm-m. In comparison, the laboratory testing indicated the shallow-most material had the same range of electrical resistivity values depending on saturation levels. The ERI also showed that there was an electrically conductive material, 7 to 70 ohm-m, that was interpreted to be clay and agreed with borehole data, however, the excavation revealed that at this depth range the geologic material varied from stratified clay to clay with cobbles to weathered residual clay. Excavation revealed that the subtle variations in the electrical conductive material corresponded well with the variations in the geologic material. We will use these results to reinterpret previously collected ERI data from the entire long-term research site.

  6. Non-invasive LC-PolScope imaging of biominerals and cell wall anisotropy changes.

    PubMed

    Eder, Magdalena; Lütz-Meindl, Ursula; Weiss, Ingrid M

    2010-10-01

    The formation of defined shapes by cells is one of the challenging questions in biology. Due to the anisotropy of cell walls and of certain biominerals, the LC-PolScope represents a promising tool for tracking dynamic structural changes in vivo non-invasively and, to some extent, quantitatively. A complex three-dimensional biogenic system, the in vitro precipitation of calcium oxalate induced by cellulose stalks produced by Dictyostelium discoideum, was analyzed. Although the retardance values and orientation of the crystals with respect to the stalk were quickly and easily detected, this study raised a number of issues that were addressed in this work. The effect of the refractive index of the embedding medium was examined by taking advantage of the homogeneous size and shape distribution of kiwifruit raphides, a biologically controlled calcium oxalate biomineral and of cotton (Gossypium) seed fibers. The retardance remained consistent when embedding these samples in media with increasing refractive indices from 1.33 to 1.42 or 1.47 for sucrose or glycerol gradients, respectively. The general applicability of LC-PolScope image processing for biominerals and cell wall formation during development in vivo was demonstrated in a particular group of green algae, the Desmidiaceae. Various organization levels of the cell wall were identified, thus confirming earlier findings based on electron microscopy and immunostaining investigations. It can be concluded that LC-PolScope microscopy is an attractive tool for studying dynamic ordering of biomolecules, such as plant cell walls, when additional parameters regarding the structure, composition, and refractive indices of the specimen are available.

  7. Application of quantum dot nanoparticles for potential non-invasive bio-imaging of mammalian spermatozoa

    USDA-ARS?s Scientific Manuscript database

    Various obstacles are encountered by mammalian spermatozoa during their journey through the female genital tract, and only few or none will reach the site of fertilization. Currently, there are limited technical approaches for non-invasive investigation of spermatozoa migration after insemination. A...

  8. Evaluation of biolistic gene transfer methods in vivo using non-invasive bioluminescent imaging techniques

    PubMed Central

    2011-01-01

    Background Gene therapy continues to hold great potential for treating many different types of disease and dysfunction. Safe and efficient techniques for gene transfer and expression in vivo are needed to enable gene therapeutic strategies to be effective in patients. Currently, the most commonly used methods employ replication-defective viral vectors for gene transfer, while physical gene transfer methods such as biolistic-mediated ("gene-gun") delivery to target tissues have not been as extensively explored. In the present study, we evaluated the efficacy of biolistic gene transfer techniques in vivo using non-invasive bioluminescent imaging (BLI) methods. Results Plasmid DNA carrying the firefly luciferase (LUC) reporter gene under the control of the human Cytomegalovirus (CMV) promoter/enhancer was transfected into mouse skin and liver using biolistic methods. The plasmids were coupled to gold microspheres (1 μm diameter) using different DNA Loading Ratios (DLRs), and "shot" into target tissues using a helium-driven gene gun. The optimal DLR was found to be in the range of 4-10. Bioluminescence was measured using an In Vivo Imaging System (IVIS-50) at various time-points following transfer. Biolistic gene transfer to mouse skin produced peak reporter gene expression one day after transfer. Expression remained detectable through four days, but declined to undetectable levels by six days following gene transfer. Maximum depth of tissue penetration following biolistic transfer to abdominal skin was 200-300 μm. Similarly, biolistic gene transfer to mouse liver in vivo also produced peak early expression followed by a decline over time. In contrast to skin, however, liver expression of the reporter gene was relatively stable 4-8 days post-biolistic gene transfer, and remained detectable for nearly two weeks. Conclusions The use of bioluminescence imaging techniques enabled efficient evaluation of reporter gene expression in vivo. Our results demonstrate that

  9. High-Resolution Harmonics Ultrasound Imaging for Non-Invasive Characterization of Wound Healing in a Pre-Clinical Swine Model

    PubMed Central

    Mathew-Steiner, Shomita S.; Dixith, Sriteja; Vanzant, Daniel; Kim, Jayne; Dickerson, Jennifer L.; Datta, Soma; Powell, Heather; Roy, Sashwati; Bergdall, Valerie; Sen, Chandan K.

    2015-01-01

    This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on the dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle imaging and dual mode (B and Doppler) ultrasound imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 and decreased thereafter. Initially, blood flow at the wound edge increased up to day 14 and subsequently regressed to baseline levels by day 21, when the wound was more than 90% closed. Coinciding with regression of blood flow at the wound edge, there was an increase in blood flow in the wound bed. This was observed to regress by day 42. Such changes in wound angiogenesis were corroborated histologically. Gated Doppler imaging quantitated the pulse pressure of the primary feeder artery supplying the wound site. This pulse pressure markedly increased with a bimodal pattern following wounding connecting it to the induction of wound angiogenesis. Finally, ultrasound elastography measured tissue stiffness and visualized growth of new tissue over time. These studies have elegantly captured the physiological sequence of events during the process of wound healing, much of which is anticipated based on certain dynamics in play, to provide the framework for future studies on molecular mechanisms driving these processes. We conclude that the tandem use of non-invasive imaging technologies has the power to provide unprecedented insight into the dynamics of the healing skin tissue. PMID:25799513

  10. Non-invasive assessment of bone quantity and quality in human trabeculae using scanning ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Xia, Yi

    Fractures and associated bone fragility induced by osteoporosis and osteopenia are widespread health threat to current society. Early detection of fracture risk associated with bone quantity and quality is important for both the prevention and treatment of osteoporosis and consequent complications. Quantitative ultrasound (QUS) is an engineering technology for monitoring bone quantity and quality of humans on earth and astronauts subjected to long duration microgravity. Factors currently limiting the acceptance of QUS technology involve precision, accuracy, single index and standardization. The objective of this study was to improve the accuracy and precision of an image-based QUS technique for non-invasive evaluation of trabecular bone quantity and quality by developing new techniques and understanding ultrasound/tissue interaction. Several new techniques have been developed in this dissertation study, including the automatic identification of irregular region of interest (iROI) in bone, surface topology mapping (STM) and mean scattering spacing (MSS) estimation for evaluating trabecular bone structure. In vitro results have shown that (1) the inter- and intra-observer errors in QUS measurement were reduced two to five fold by iROI compared to previous results; (2) the accuracy of QUS parameter, e.g., ultrasound velocity (UV) through bone, was improved 16% by STM; and (3) the averaged trabecular spacing can be estimated by MSS technique (r2=0.72, p<0.01). The measurement errors of BUA and UV introduced by the soft tissue and cortical shells in vivo can be quantified by developed foot model and simplified cortical-trabecular-cortical sandwich model, which were verified by the experimental results. The mechanisms of the errors induced by the cortical and soft tissues were revealed by the model. With developed new techniques and understanding of sound-tissue interaction, in vivo clinical trail and bed rest study were preformed to evaluate the performance of QUS in

  11. Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by non-invasive imaging

    PubMed Central

    Ren, Pei-Gen; Huang, Zhinong; Ma, Ting; Biswal, Sandip; Smith, Robert L.; Goodman, Stuart B.

    2010-01-01

    Macrophages constitute a major part of the cell response to wear particles produced at articulating and non-articulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by non-invasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/ml UHMWPE suspension, or saline alone. Reporter RAW264.7 macrophages which stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection, and at 2-day intervals. Compared to the non-operated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 ± 0.09, 2.36 ± 0.92, and 10.32 ± 7.61 fold, respectively. The values at same time points for saline injected control group were 1.08 ± 0.07, 1.14 ± 0.27, and 1.14 ± 0.35 fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all post-injection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle-induced periprosthetic osteolysis. PMID:20213815

  12. Biomarkers for radiation pneumonitis using non-invasive molecular imaging

    PubMed Central

    Medhora, Meetha; Haworth, Steven; Liu, Yu; Narayanan, Jayashree; Gao, Feng; Zhao, Ming; Audi, Said; Jacobs, Elizabeth R.; Fish, Brian L.; Clough, Anne V.

    2016-01-01

    Rationale Our goal is to develop minimally-invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in case of radiological terrorism. Our previous studies have shown a single dose of 15 Gy X-rays to the thorax causes severe pneumonitis in rats by 6–8 weeks. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 weeks after radiation. Methods We used two functional single photon emission computed tomography (SPECT) probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of technetium labeled macroaggregated albumin (99mTc-MAA). Perfused volume was determined by comparing the volume of distribution of 99mTc-MAA to the anatomical lung volume obtained by micro-CT. A second probe, technetium labeled duramycin that binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. Results Perfused volume of lung was decreased by ~25% at 1, 2 and 3 weeks after 15 Gy and 99mTc-duramycin uptake was more than doubled at 2 and 3 weeks. There was no change in body weight, breathing rate or lung histology between irradiated and non-irradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 weeks after 15 Gy. Principal conclusions Our results suggest the potential for SPECT biomarkers for predicting radiation injury to the lungs before substantial functional or histological damage is observed. Early prediction of radiation pneumonitis will benefit those receiving radiation in the context of therapy, accidents or terrorism in time to initiate mitigation. PMID:27033892

  13. Evaluation of BEBIG HDR 60Co system for non-invasive image-guided breast brachytherapy

    PubMed Central

    Zehtabian, Mehdi; Sina, Sedigheh; Rivard, Mark J.

    2015-01-01

    Purpose HDR 60Co system has recently been developed and utilized for brachytherapy in many countries outside of the U.S. as an alternative to 192Ir. In addition, the AccuBoost® technique has been demonstrated to be a successful non-invasive image-guided breast brachytherapy treatment option. The goal of this project is to evaluate the possibility of utilizing the BEBIG HDR 60Co system for AccuBoost treatment. These evaluations are performed with Monte Carlo (MC) simulation technique. Material and methods In this project, the MC calculated dose distributions from HDR 60Co for various breast sizes have been compared with the simulated data using an HDR 192Ir source. These calculations were performed using the MCNP5 code. The initial calculations were made with the same applicator dimensions as the ones used with the HDR 192Ir system (referred here after as standard applicator). The activity of the 60Co source was selected such that the dose at the center of the breast would be the same as the values from the 192Ir source. Then, the applicator wall-thickness for the HDR 60Co system was increased to diminish skin dose to levels received when using the HDR 192Ir system. With this geometry, dose values to the chest wall and the skin were evaluated. Finally, the impact of a conical attenuator with the modified applicator for the HDR 60Co system was analyzed. Results These investigations demonstrated that loading the 60Co sources inside the thick-walled applicators created similar dose distributions to those of the 192Ir source in the standard applicators. However, dose to the chest wall and breast skin with 60Co source was reduced using the thick-walled applicators relative to the standard applicators. The applicators with conical attenuator reduced the skin dose for both source types. Conclusions The AccuBoost treatment can be performed with the 60Co source and thick-wall applicators instead of 192Ir with standard applicators. PMID:26816504

  14. Evaluation of BEBIG HDR (60)Co system for non-invasive image-guided breast brachytherapy.

    PubMed

    Zehtabian, Mehdi; Sina, Sedigheh; Rivard, Mark J; Meigooni, Ali S

    2015-12-01

    HDR (60)Co system has recently been developed and utilized for brachytherapy in many countries outside of the U.S. as an alternative to (192)Ir. In addition, the AccuBoost(®) technique has been demonstrated to be a successful non-invasive image-guided breast brachytherapy treatment option. The goal of this project is to evaluate the possibility of utilizing the BEBIG HDR (60)Co system for AccuBoost treatment. These evaluations are performed with Monte Carlo (MC) simulation technique. In this project, the MC calculated dose distributions from HDR (60)Co for various breast sizes have been compared with the simulated data using an HDR (192)Ir source. These calculations were performed using the MCNP5 code. The initial calculations were made with the same applicator dimensions as the ones used with the HDR (192)Ir system (referred here after as standard applicator). The activity of the (60)Co source was selected such that the dose at the center of the breast would be the same as the values from the (192)Ir source. Then, the applicator wall-thickness for the HDR (60)Co system was increased to diminish skin dose to levels received when using the HDR (192)Ir system. With this geometry, dose values to the chest wall and the skin were evaluated. Finally, the impact of a conical attenuator with the modified applicator for the HDR (60)Co system was analyzed. These investigations demonstrated that loading the (60)Co sources inside the thick-walled applicators created similar dose distributions to those of the (192)Ir source in the standard applicators. However, dose to the chest wall and breast skin with (60)Co source was reduced using the thick-walled applicators relative to the standard applicators. The applicators with conical attenuator reduced the skin dose for both source types. The AccuBoost treatment can be performed with the (60)Co source and thick-wall applicators instead of (192)Ir with standard applicators.

  15. Non-Invasive Early Detection and Molecular Analysis of Low X-ray Dose Effects in the Lens

    SciTech Connect

    Goldstein, Lee

    2014-07-02

    This is the Final Progress Report for DOE-funded research project DE-PS02-08ER08-01 titled “Non-Invasive Early Detection and Molecular Analysis of Low X-ray Dose Effects in the Lens”. The project focuses on the effects of low-linear energy transfer (LET) radiation on the ocular lens. The lens is an exquisitely radiosensitive tissue with a highly-ordered molecular structure that is amenable to non-invasive optical study from the periphery. These merits point to the lens as an ideal target for laser-based molecular biodosimetry (MBD). Following exposure to different types of ionizing radiations, the lens demonstrates molecular changes (e.g., oxidation, racemization, crosslinkage, truncation, aggregation, etc.) that impact the structure and function of the long-lived proteins in the cytosol of lens fiber cells. The vast majority of proteins in the lens comprise the highly-ordered crystallins. These highly conserved lens proteins are amongst the most concentrated and stable in the body. Once synthesized, the crystallins are retained in the fiber cell cytoplasm for life. Taken together, these properties point to the lens as an ideal system for quantitative in vivo MBD assessment using quasi-elastic light scattering (QLS) analysis. In this project, we deploy a purpose-designed non-invasive infrared laser QLS instrument as a quantitative tool for longitudinal assessment of pre-cataractous molecular changes in the lenses of living mice exposed to low-dose low-LET radiation compared to non-irradiated sham controls. We hypothesize that radiation exposure will induce dose-dependent changes in the molecular structure of matrix proteins in the lens. Mechanistic assays to ascertain radiation-induced molecular changes in the lens focus on protein aggregation and gene/protein expression patterns. We anticipate that this study will contribute to our understanding of early molecular changes associated with radiation-induced tissue pathology. This study also affords potential for

  16. In vivo fibered confocal reflectance imaging: totally non-invasive morphological cellular imaging brought to the endoscopist

    NASA Astrophysics Data System (ADS)

    Osdoit, Anne; Genet, Magalie; Perchant, Aymeric; Loiseau, Sacha; Abrat, Benjamin; Lacombe, François

    2006-02-01

    This paper presents a novel fibered confocal reflectance microscopy system (FCRM) specifically designed for the medical observation of biological tissues in vivo and in situ, in real time, at the cellular level: the R-600. Reflectance imaging is based on the refraction index difference between biological components while confocal imaging allow to perform the optical sectioning slice in-depth inside the tissues. The R-600 is based on a proximal scanning system, coupled with a 7 mm diameter probe made of tens of thousands of flexible optical fibers allowing in situ imaging, associated with a dedicated software performing real-time control and image processing. The R-600 provides 12 frames per second at an optical imaging depth of 30 microns, with a high lateral resolution, 1 micron, an axial resolution of 2 microns in a field of view 160 microns in diameter. Thanks to the miniaturization of the optical probe, unprecedented accessibility is made possible in organs such as the cervix or the otolaryngological sphere, in a completely non-invasive fashion. The aim of FCRM is to perform optical biopsy. As a first step towards this goal, we present here results obtained in vivo and in real-time on a human mouth , assessing the ability of the R-600 to perform rapid morphologic examination. Subcellular structures such as nuclei and membranes can be clearly distinguished on the images. Further miniaturization opens perspectives for an integrated endoscope-compatible system with broad medical applications.

  17. Non-Invasive Optical Imaging of Eosinophilia during the Course of an Experimental Allergic Airways Disease Model and in Response to Therapy

    PubMed Central

    Markus, M. Andrea; Dullin, Christian; Mitkovski, Miso; Prieschl-Grassauer, Eva; Epstein, Michelle M.; Alves, Frauke

    2014-01-01

    Background Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils. Methodology/Principal Findings An ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h–72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs. Conclusion/Significance We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time. PMID:24587190

  18. Non-invasive optical imaging of eosinophilia during the course of an experimental allergic airways disease model and in response to therapy.

    PubMed

    Markus, M Andrea; Dullin, Christian; Mitkovski, Miso; Prieschl-Grassauer, Eva; Epstein, Michelle M; Alves, Frauke

    2014-01-01

    Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils. An ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h-72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs. We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time.

  19. Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations

    PubMed Central

    Gilbert, Jessica R.; Symmonds, Mkael; Hanna, Michael G.; Dolan, Raymond J.; Friston, Karl J.; Moran, Rosalyn J.

    2016-01-01

    Clinical assessments of brain function rely upon visual inspection of electroencephalographic waveform abnormalities in tandem with functional magnetic resonance imaging. However, no current technology proffers in vivo assessments of activity at synapses, receptors and ion-channels, the basis of neuronal communication. Using dynamic causal modeling we compared electrophysiological responses from two patients with distinct monogenic ion channelopathies and a large cohort of healthy controls to demonstrate the feasibility of assaying synaptic-level channel communication non-invasively. Synaptic channel abnormality was identified in both patients (100% sensitivity) with assay specificity above 89%, furnishing estimates of neurotransmitter and voltage-gated ion throughput of sodium, calcium, chloride and potassium. This performance indicates a potential novel application as an adjunct for clinical assessments in neurological and psychiatric settings. More broadly, these findings indicate that biophysical models of synaptic channels can be estimated non-invasively, having important implications for advancing human neuroimaging to the level of non-invasive ion channel assays. PMID:26342528

  20. Nano-sized Contrast Agents to Non-Invasively Detect Renal Inflammation by Magnetic Resonance Imaging

    PubMed Central

    Thurman, Joshua M.; Serkova, Natalie J.

    2013-01-01

    Several molecular imaging methods have been developed that employ nano-sized contrast agents to detect markers of inflammation within tissues. Renal inflammation contributes to disease progression in a wide range of autoimmune and inflammatory diseases, and a biopsy is currently the only method of definitively diagnosing active renal inflammation. However, the development of new molecular imaging methods that employ contrast agents capable of detecting particular immune cells or protein biomarkers will allow clinicians to evaluate inflammation throughout the kidneys, and to assess a patient's response to immunomodulatory drugs. These imaging tools will improve our ability to validate new therapies and to optimize the treatment of individual patients with existing therapies. This review describes the clinical need for new methods of monitoring renal inflammation, and recent advances in the development of nano-sized contrast agents for detection of inflammatory markers of renal disease. PMID:24206601

  1. X-ray excited luminescent chemical imaging (XELCI) for non-invasive imaging of implant infections

    NASA Astrophysics Data System (ADS)

    Benza, Donald; Uzair, Unaiza; Raval, Yash; Tzeng, Tzuen-Rong J.; Behrend, Caleb J.; Anker, Jeffrey N.

    2017-02-01

    X-ray excited luminescent chemical imaging (XELCI) uses a combination of X-ray excitation to provide high resolution and optical detection to provide chemical sensing. A key application is to detect and study implant-associated infection. The implant is coated with a layer of X-ray scintillators which generate visible near infrared light when irradiated with an X-ray beam. This light first passes through a pH indicator dye-loaded film placed over the scintillator film in order to modulate the luminescence spectrum according to pH. The light then passes through tissue is collected and the spectral ratio measured to determine pH. A focused X-ray beam irradiates a point in the scintillator film, and a pH image is formed point-by-point by scanning the beam across the sample. The sensor and scanning system are described along with preliminary results showing images in rabbit models.

  2. Non-invasive imaging methods applied to neo- and paleontological cephalopod research

    NASA Astrophysics Data System (ADS)

    Hoffmann, R.; Schultz, J. A.; Schellhorn, R.; Rybacki, E.; Keupp, H.; Gerden, S. R.; Lemanis, R.; Zachow, S.

    2013-11-01

    Several non-invasive methods are common practice in natural sciences today. Here we present how they can be applied and contribute to current topics in cephalopod (paleo-) biology. Different methods will be compared in terms of time necessary to acquire the data, amount of data, accuracy/resolution, minimum-maximum size of objects that can be studied, of the degree of post-processing needed and availability. Main application of the methods is seen in morphometry and volumetry of cephalopod shells in order to improve our understanding of diversity and disparity, functional morphology and biology of extinct and extant cephalopods.

  3. Non-Invasive MRI and Spectroscopy of mdx Mice Reveal Temporal Changes in Dystrophic Muscle Imaging and in Energy Deficits

    PubMed Central

    Heier, Christopher R.; Guerron, Alfredo D.; Korotcov, Alexandru; Lin, Stephen; Gordish-Dressman, Heather; Fricke, Stanley; Sze, Raymond W.; Hoffman, Eric P.; Wang, Paul; Nagaraju, Kanneboyina

    2014-01-01

    In Duchenne muscular dystrophy (DMD), a genetic disruption of dystrophin protein expression results in repeated muscle injury and chronic inflammation. Magnetic resonance imaging shows promise as a surrogate outcome measure in both DMD and rehabilitation medicine that is capable of predicting clinical benefit years in advance of functional outcome measures. The mdx mouse reproduces the dystrophin deficiency that causes DMD and is routinely used for preclinical drug testing. There is a need to develop sensitive, non-invasive outcome measures in the mdx model that can be readily translatable to human clinical trials. Here we report the use of magnetic resonance imaging and spectroscopy techniques for the non-invasive monitoring of muscle damage in mdx mice. Using these techniques, we studied dystrophic mdx muscle in mice from 6 to 12 weeks of age, examining both the peak disease phase and natural recovery phase of the mdx disease course. T2 and fat-suppressed imaging revealed significant levels of tissue with elevated signal intensity in mdx hindlimb muscles at all ages; spectroscopy revealed a significant deficiency of energy metabolites in 6-week-old mdx mice. As the mdx mice progressed from the peak disease stage to the recovery stage of disease, each of these phenotypes was either eliminated or reduced, and the cross-sectional area of the mdx muscle was significantly increased when compared to that of wild-type mice. Histology indicates that hyper-intense MRI foci correspond to areas of dystrophic lesions containing inflammation as well as regenerating, degenerating and hypertrophied myofibers. Statistical sample size calculations provide several robust measures with the ability to detect intervention effects using small numbers of animals. These data establish a framework for further imaging or preclinical studies, and they support the development of MRI as a sensitive, non-invasive outcome measure for muscular dystrophy. PMID:25390038

  4. Non-invasive cardiac imaging techniques and vascular tools for the assessment of cardiovascular disease in type 2 diabetes mellitus.

    PubMed

    Djaberi, R; Beishuizen, E D; Pereira, A M; Rabelink, T J; Smit, J W; Tamsma, J T; Huisman, M V; Jukema, J W

    2008-09-01

    Cardiovascular disease is the major cause of mortality in type 2 diabetes mellitus. The criteria for the selection of those asymptomatic patients with type 2 diabetes who should undergo cardiac screening and the therapeutic consequences of screening remain controversial. Non-invasive techniques as markers of atherosclerosis and myocardial ischaemia may aid risk stratification and the implementation of tailored therapy for the patient with type 2 diabetes. In the present article we review the literature on the implementation of non-invasive vascular tools and cardiac imaging techniques in this patient group. The value of these techniques as endpoints in clinical trials and as risk estimators in asymptomatic diabetic patients is discussed. Carotid intima-media thickness, arterial stiffness and flow-mediated dilation are abnormal long before the onset of type 2 diabetes. These vascular tools are therefore most likely to be useful for the identification of 'at risk' patients during the early stages of atherosclerotic disease. The additional value of these tools in risk stratification and tailored therapy in type 2 diabetes remains to be proven. Cardiac imaging techniques are more justified in individuals with a strong clinical suspicion of advanced coronary heart disease (CHD). Asymptomatic myocardial ischaemia can be detected by stress echocardiography and myocardial perfusion imaging. The more recently developed non-invasive multi-slice computed tomography angiography is recommended for exclusion of CHD, and can therefore be used to screen asymptomatic patients with type 2 diabetes, but has the associated disadvantages of high radiation exposure and costs. Therefore, we propose an algorithm for the screening of asymptomatic diabetic patients, the first step of which consists of coronary artery calcium score assessment and exercise ECG.

  5. Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

    2015-01-01

    One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

  6. Visceral anatomy of ocean sunfish (Mola mola (L., 1758), Molidae, Tetraodontiformes) and angler (Lophius piscatorius (L., 1758), Lophiidae, Lophiiformes) investigated by non-invasive imaging techniques.

    PubMed

    Chanet, Bruno; Guintard, Claude; Boisgard, Thierry; Fusellier, Marion; Tavernier, Cédric; Betti, Eric; Madec, Stéphane; Richaudeau, Yvan; Raphaël, Christian; Dettaï, Agnès; Lecointre, Guillaume

    2012-12-01

    The purpose of this work is to examine the gross visceral anatomy of ocean sunfish and angler using non-invasive imaging techniques: computed tomography imaging (CT) and magnetic resonance imaging (MRI). Similarities and differences in the internal organisation of these two species are verified. Both species lack a swimbladder and present a significant asymmetry in the hepatic lobes, an elongated bile duct terminating close to the stomach, a compact thyroid embedded in a blood lacuna, and very reduced brain and spinal cord. These observations are important in regard to the close relationships between Tetraodontiformes and Lophiiformes, established by several molecular works, but not yet confirmed by morpho-anatomical data. However the occurrence of these features has to be examined in other taxa before phylogenetic hypotheses are proposed.

  7. Non-invasive fluorescent-protein imaging of orthotopic pancreatic-cancer-patient tumorgraft progression in nude mice.

    PubMed

    Suetsugu, Atsushi; Katz, Matthew; Fleming, Jason; Truty, Mark; Thomas, Ryan; Saji, Shigetoyo; Moriwaki, Hisataka; Bouvet, Michael; Hoffman, Robert M

    2012-08-01

    In order to individualize and therefore have more effective treatment for pancreatic cancer, we have developed a multicolor, imageable, orthotopic mouse model for individual patients with pancreatic cancer by passaging their tumors through transgenic nude mice expressing green fluorescent protein (GFP) and red fluorescent protein (RFP). The tumors acquired brightly fluorescent stroma from the transgenic host mice, which was stably associated with the tumors through multiple passages. In the present study, pancreatic cancer patient tumor specimens were initially established in NOD.CB17-Prkdc(scid)/NcrCrl (NOD/SCID) mice. The tumors were then passaged orthotopically into transgenic nude mice ubiquitously expressing GFP and subsequently to nude mice ubiquitously expressing RFP. The tumors, with very bright GFP and RFP stroma, were then orthotopically passaged to non-transgenic nude mice. It was possible to image the brightly fluorescent tumors non-invasively longitudinally as they progressed in the non-transgenic nude mice. This non-invasive imageable tumorgraft model will be valuable to screen for effective treatment options for individual patients with pancreatic cancer, as well as for the discovery of improved agents for this treatment-resistant disease.

  8. Application of fluorescence spectroscopy and multispectral imaging for non-invasive estimation of GFP transfection efficiency

    NASA Astrophysics Data System (ADS)

    Tamošiūnas, M.; Jakovels, D.; Lihačovs, A.; Kilikevičius, A.; Baltušnikas, J.; Kadikis, R.; Šatkauskas, S.

    2014-10-01

    Electroporation and ultrasound induced sonoporation has been showed to induce plasmid DNA transfection to the mice tibialis cranialis muscle. It offers new prospects for gene therapy and cancer treatment. However, numerous experimental data are still needed to deliver the plausible explanation of the mechanisms governing DNA electro- or sono-transfection, as well as to provide the updates on transfection protocols for transfection efficiency increase. In this study we aimed to apply non-invasive optical diagnostic methods for the real time evaluation of GFP transfection levels at the reduced costs for experimental apparatus and animal consumption. Our experimental set-up allowed monitoring of GFP levels in live mice tibialis cranialis muscle and provided the parameters for DNA transfection efficiency determination.

  9. Non-Invasive Imaging Demonstrates Clinical Features of Ankylosing Spondylitis in a Rat Adjuvant Model: a Case Study

    PubMed Central

    Dawson, J.; Kolbinger, F.; Kramer, I.; Beckmann, N.

    2016-01-01

    Main features of ankylosing spondylitis like inflammatory erosive osteopenia and bony overgrowth are recapitulated in rats challenged with complete Freund’s adjuvant. In vivo changes induced in the rat spine were followed longitudinally by magnetic resonance imaging (MRI) and assessed terminally by micro-computerized tomography (micro-CT) and histology. Signals reflecting inflammation were detected by MRI at levels L5-L6 throughout the experiment, peaking at day 27 after adjuvant. Bone erosion and formation occurred from this time point onward, as confirmed by micro-CT. Histology confirmed the inflammation and bone remodeling. The present study demonstrates the potential of imaging for longitudinal assessments of spinal changes in this animal model and the excellent correlation between in vivo images and histology underlines its fundamental role in the validation of non-invasive imaging. PMID:28076929

  10. Non-invasive continuous imaging of drug release from soy-based skin equivalent using wide-field interferometry

    NASA Astrophysics Data System (ADS)

    Gabai, Haniel; Baranes-Zeevi, Maya; Zilberman, Meital; Shaked, Natan T.

    2013-04-01

    We propose an off-axis interferometric imaging system as a simple and unique modality for continuous, non-contact and non-invasive wide-field imaging and characterization of drug release from its polymeric device used in biomedicine. In contrast to the current gold-standard methods in this field, usually based on chromatographic and spectroscopic techniques, our method requires no user intervention during the experiment, and only one test-tube is prepared. We experimentally demonstrate imaging and characterization of drug release from soy-based protein matrix, used as skin equivalent for wound dressing with controlled anesthetic, Bupivacaine drug release. Our preliminary results demonstrate the high potential of our method as a simple and low-cost modality for wide-field imaging and characterization of drug release from drug delivery devices.

  11. Non-invasive, Contrast-enhanced Spectral Imaging of Breast Cancer Signatures in Preclinical Animal Models In vivo

    PubMed Central

    Ramanujan, V Krishnan; Ren, Songyang; Park, Sangyong; Farkas, Daniel L

    2011-01-01

    We report here a non-invasive multispectral imaging platform for monitoring spectral reflectance and fluorescence images from primary breast carcinoma and metastatic lymph nodes in preclinical rat model in vivo. The system is built around a monochromator light source and an acousto-optic tunable filter (AOTF) for spectral selection. Quantitative analysis of the measured reflectance profiles in the presence of a widely-used lymphazurin dye clearly demonstrates the capability of the proposed imaging platform to detect tumor-associated spectral signatures in the primary tumors as well as metastatic lymphatics. Tumor-associated changes in vascular oxygenation and interstitial fluid pressure are reasoned to be the physiological sources of the measured reflectance profiles. We also discuss the translational potential of our imaging platform in intra-operative clinical setting. PMID:21572915

  12. Non-invasive localization of thymol accumulation in Carum copticum (Apiaceae) fruits by chemical shift selective magnetic resonance imaging.

    PubMed

    Gersbach, P V; Reddy, N

    2002-08-01

    Magnetic resonance imaging was used to localize the site of essential oil accumulation in fruit of Carum copticum L. (Apiaceae). A chemical shift method is described that utilized the spectral properties of the aromatic monoterpene thymol, the major component of the essential oil, to image thymol selectively. The presence of essential oil secretory structures in the fruit and an essential oil containing a high proportion of thymol were confirmed with optical microscopy and gas chromatography-mass spectrometry, respectively. Selective imaging of whole C. copticum fruits showed that thymol accumulation was localized to the secretory structures (canals) situated in the fruit wall. The technique was considered non-invasive as the seeds used in the imaging experiments remained intact and viable.

  13. A New Imaging Platform for Visualizing Biological Effects of Non-Invasive Radiofrequency Electric-Field Cancer Hyperthermia

    PubMed Central

    Corr, Stuart J.; Shamsudeen, Sabeel; Vergara, Leoncio A.; Ho, Jason Chak-Shing; Ware, Matthew J.; Keshishian, Vazrik; Yokoi, Kenji; Savage, David J.; Meraz, Ismail M.; Kaluarachchi, Warna; Cisneros, Brandon T.; Raoof, Mustafa; Nguyen, Duy Trac; Zhang, Yingchun; Wilson, Lon J.; Summers, Huw; Rees, Paul; Curley, Steven A.; Serda, Rita E.

    2015-01-01

    Herein, we present a novel imaging platform to study the biological effects of non-invasive radiofrequency (RF) electric field cancer hyperthermia. This system allows for real-time in vivo intravital microscopy (IVM) imaging of radiofrequency-induced biological alterations such as changes in vessel structure and drug perfusion. Our results indicate that the IVM system is able to handle exposure to high-power electric-fields without inducing significant hardware damage or imaging artifacts. Furthermore, short durations of low-power (< 200 W) radiofrequency exposure increased transport and perfusion of fluorescent tracers into the tumors at temperatures below 41°C. Vessel deformations and blood coagulation were seen for tumor temperatures around 44°C. These results highlight the use of our integrated IVM-RF imaging platform as a powerful new tool to visualize the dynamics and interplay between radiofrequency energy and biological tissues, organs, and tumors. PMID:26308617

  14. Simplified Models of Non-Invasive Fractional Flow Reserve Based on CT Images

    PubMed Central

    Zhang, Jun-Mei; Zhong, Liang; Luo, Tong; Lomarda, Aileen Mae; Huo, Yunlong; Yap, Jonathan; Lim, Soo Teik; Tan, Ru San; Wong, Aaron Sung Lung; Tan, Jack Wei Chieh; Yeo, Khung Keong; Fam, Jiang Ming; Keng, Felix Yung Jih; Wan, Min; Su, Boyang; Zhao, Xiaodan; Allen, John Carson; Kassab, Ghassan S.; Chua, Terrance Siang Jin; Tan, Swee Yaw

    2016-01-01

    Invasive fractional flow reserve (FFR) is the gold standard to assess the functional coronary stenosis. The non-invasive assessment of diameter stenosis (DS) using coronary computed tomography angiography (CTA) has high false positive rate in contrast to FFR. Combining CTA with computational fluid dynamics (CFD), recent studies have shown promising predictions of FFRCT for superior assessment of lesion severity over CTA alone. The CFD models tend to be computationally expensive, however, and require several hours for completing analysis. Here, we introduce simplified models to predict noninvasive FFR at substantially less computational time. In this retrospective pilot study, 21 patients received coronary CTA. Subsequently a total of 32 vessels underwent invasive FFR measurement. For each vessel, FFR based on steady-state and analytical models (FFRSS and FFRAM, respectively) were calculated non-invasively based on CTA and compared with FFR. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 90.6% (87.5%), 80.0% (80.0%), 95.5% (90.9%), 88.9% (80.0%) and 91.3% (90.9%) respectively for FFRSS (and FFRAM) on a per-vessel basis, and were 75.0%, 50.0%, 86.4%, 62.5% and 79.2% respectively for DS. The area under the receiver operating characteristic curve (AUC) was 0.963, 0.954 and 0.741 for FFRSS, FFRAM and DS respectively, on a per-patient level. The results suggest that the CTA-derived FFRSS performed well in contrast to invasive FFR and they had better diagnostic performance than DS from CTA in the identification of functionally significant lesions. In contrast to FFRCT, FFRSS requires much less computational time. PMID:27187726

  15. Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs

    PubMed Central

    Jiji, Ronny S.; Kramer, Christopher M.; Salerno, Michael

    2012-01-01

    Cardiotoxicity due to administration of cancer therapeutic agents such as anthracyclines and herceptin are well described. Established guidelines to screen for chemotherapy-related cardiotoxicity (CRC) are primarily based on serial assessment of left ventricular (LV) ejection fraction (EF). However, other parameters such as LV volume, diastolic function, and strain may also be useful in screening for cardiotoxicity. More recent advances in molecular imaging of apoptosis and tissue characterization by cardiac MRI are techniques which might allow early detection of patients at high risk for developing cardiotoxicity prior to a drop in EF. This comprehensive multi-modality review will discuss both the current established imaging techniques as well as the emerging technologies which may revolutionize the future of screening and evaluation for CRC. PMID:22351492

  16. Multi-Parametric Monitoring of Tumor Response to Chemotherapy by Non-Invasive Imaging

    PubMed Central

    Medarova, Zdravka; Rashkovetsky, Leonid; Pantazopoulos, Pamela; Moore, Anna

    2008-01-01

    With the emerging concept of individualized cancer therapy, it becomes crucial to develop methods for the noninvasive assessment of treatment outcome. With this in mind, we designed a novel approach for the comprehensive evaluation of response to chemotherapy with the established agent doxorubicin in a pre-clinical breast cancer model. This approach delivers information not only about change in tumor size but also about target antigen expression. Our strategy relies on a tumor-specific contrast agent (MN-EPPT) targeting the underglycosylated MUC-1 (uMUC-1) tumor antigen, found on over 90% of breast cancers and predictive of chemotherapeutic response. MN-EPPT consists of superparamagnetic iron oxide nanoparticles (MN) for magnetic resonance imaging, modified with Cy5.5 dye (for near-infrared fluorescence optical imaging, NIRF), and conjugated to peptides (EPPT), specifically recognizing uMUC-1. In vivo, treatment of mice bearing orthotopic human breast carcinomas with doxorubicin led to a reduction in tumor mass and resulted in downregulation of uMUC-1. The tumor-specific accumulation of MN-EPPT allowed the assessment of change in tumor volume by noninvasive imaging. Furthermore, in mice injected with MN-EPPT, tumor delta-T2 was significantly reduced after treatment with doxorubicin, indicating a lower accumulation of MN-EPPT and reflecting the reduced expression of uMUC-1. With these studies, we have demonstrated the utility of magnetic resonance imaging for the multiparametric characterization of breast tumor response to chemotherapy. This approach has the potential of significantly advancing our ability to better direct the development of molecularly-targeted individualized therapy protocols, since it permits the monitoring of therapy on a molecular scale. PMID:19141648

  17. Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma

    PubMed Central

    GHITA, MIHAELA A.; CARUNTU, CONSTANTIN; ROSCA, ADRIAN E.; KALESHI, HARILLAQ; CARUNTU, ANA; MORARU, LILIANA; DOCEA, ANCA OANA; ZURAC, SABINA; BODA, DANIEL; NEAGU, MONICA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Superficial basal cell carcinoma (sBCC) is the second most frequent histological type of basal cell carcinoma (BCC), usually requiring a skin biopsy to confirm the diagnosis. It usually appears on the upper trunk and shoulders as erythematous and squamous lesions. Although it has a slow growth and seldom metastasizes, early diagnosis and management are of crucial importance in preventing local invasion and subsequent disfigurement. Dermoscopy is nowadays an indispensable tool for the dermatologist when evaluating skin tumors. Reflectance confocal microscopy (RCM) is a novel imaging technique that allows the non-invasive, in vivo quasi-microscopic morphological and dynamic assessment of superficial skin tumors. Moreover, it offers the advantage of performing infinite repeatable determinations to monitor disease progression and non-surgical treatment for sBCC. Herein, we present three lesions of sBCC evaluated using in vivo and non-invasive imaging techniques, emphasizing the usefulness of combining RCM with dermoscopy for increasing the diagnostic accuracy of sBCC. PMID:27123056

  18. Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma.

    PubMed

    Ghita, Mihaela A; Caruntu, Constantin; Rosca, Adrian E; Kaleshi, Harillaq; Caruntu, Ana; Moraru, Liliana; Docea, Anca Oana; Zurac, Sabina; Boda, Daniel; Neagu, Monica; Spandidos, Demetrios A; Tsatsakis, Aristidis M

    2016-05-01

    Superficial basal cell carcinoma (sBCC) is the second most frequent histological type of basal cell carcinoma (BCC), usually requiring a skin biopsy to confirm the diagnosis. It usually appears on the upper trunk and shoulders as erythematous and squamous lesions. Although it has a slow growth and seldom metastasizes, early diagnosis and management are of crucial importance in preventing local invasion and subsequent disfigurement. Dermoscopy is nowadays an indispensable tool for the dermatologist when evaluating skin tumors. Reflectance confocal microscopy (RCM) is a novel imaging technique that allows the non-invasive, in vivo quasi-microscopic morphological and dynamic assessment of superficial skin tumors. Moreover, it offers the advantage of performing infinite repeatable determinations to monitor disease progression and non-surgical treatment for sBCC. Herein, we present three lesions of sBCC evaluated using in vivo and non-invasive imaging techniques, emphasizing the usefulness of combining RCM with dermoscopy for increasing the diagnostic accuracy of sBCC.

  19. Spectroscopic imaging of blood vessels only near the skin surface for non-invasive blood glucose measurement

    NASA Astrophysics Data System (ADS)

    Fujiwara, Masaru; Sato, Shun; Abeygunawardhana, Pradeep K. W.; Suzuki, Satoru; Nishiyama, Akira; Wada, Kenji; Ishimaru, Ichiro

    2015-07-01

    To realize the non-invasive blood glucose measurement, it will be effective to acquire the spectroscopic imaging of blood vessels only near the skin surface for eliminating other biological-component's disturbances. Our proposed imaging-type 2-dimensional Fourier spectroscopic imaging can limit the measuring depth into focal plane with high light detection sensitivity. Thus, the proposed method will be suitable for measuring only near the skin surface with detecting weak reflected light from inner biomembrane. But reflectance of skin surface is more than 1000 times larger than inner skin's reflectance. Paying attention on Fresnel reflection, fingers what were illuminated by p-polarized beam from Brewster's angle were observed with crossed-Nicol dark field optics. We successfully acquired spectroscopic characteristics of hemoglobin at vein area near the skin surface.

  20. Detection of DSS-induced gastrointestinal mucositis in mice by non-invasive optical near-infrared (NIR) imaging of cathepsin activity.

    PubMed

    Finnberg, Niklas K; Liu, Yvette; El-Deiry, Wafik S

    2013-08-01

    Approximately 1.4 million people of the US population suffer from Inflammatory Bowel Disease (IBD) of which the most common conditions are ulcerative colitis (UC) and Crohn disease (CD). Colonoscopy and small bowel follow through are considered the current gold standard in diagnosing IBD. However, improved imaging and increased diagnostic sensitivity could be beneficial. Optical molecular imaging has the potential to become a powerful and practical tool for early detection, image-guided biopsy, and surgery in diagnosing and treating patients with IBD. Here we used a well characterized chemical model to initiate experimental IBD in mice by feeding with dextran sulfate sodium (DSS) containing drinking water in an attempt to investigate the utility of non-invasive infrared (NIR) optical imaging in the detection gastrointestinal (GI) injury. We employed a "smart probe" (ProSense680) cleaved and fluorescently activated in the NIR-spectrum by various forms of secreted cathepsins. This probe has previously been shown to serve as a biomarker for the homing of inflammatory cells to injury. Our investigation suggests that NIR optical imaging can detect cathepsin-dependent probe cleavage non-invasively in animals with DSS-induced IBD. Increased tissue probe-retention and fluorescence was associated with increased infiltration of inflammatory cells, epithelial atrophy and sterilization of the mucosa. Furthermore, using NIR-imaging ex vivo we were able to document regional "hot spots" of inflammatory damage to the large intestine suggesting this method potentially could be coupled with colonoscopy investigation to aid in the sampling and the diagnostics of IBD.

  1. Next-generation Raman tomography instrument for non-invasive in vivo bone imaging

    PubMed Central

    Demers, Jennifer-Lynn H.; Esmonde-White, Francis W.L.; Esmonde-White, Karen A.; Morris, Michael D.; Pogue, Brian W.

    2015-01-01

    Combining diffuse optical tomography methods with Raman spectroscopy of tissue provides the ability for in vivo measurements of chemical and molecular characteristics, which have the potential for being useful in diagnostic imaging. In this study a system for Raman tomography was developed and tested. A third generation microCT coupled system was developed to combine 10 detection fibers and 5 excitation fibers with laser line filtering and a Cytop reference signal. Phantom measurements of hydroxyapatite concentrations from 50 to 300 mg/ml had a linear response. Fiber placement and experiment design was optimized using cadaver animals with live animal measurements acquired to validate the systems capabilities. Promising results from the initial animal experiments presented here, pave the way for a study of longitudinal measurements during fracture healing and the scaling of the Raman tomography system towards human measurements. PMID:25798304

  2. Ultrasound imaging of propagation of myocardial contraction for non-invasive identification of myocardial ischemia

    NASA Astrophysics Data System (ADS)

    Matsuno, Yuya; Taki, Hirofumi; Yamamoto, Hiroaki; Hirano, Michinori; Morosawa, Susumu; Shimokawa, Hiroaki; Kanai, Hiroshi

    2017-07-01

    Non-invasive identification of ischemic regions is important for diagnosis and treatment of myocardial infarction. In the present study, ultrasound measurement was applied to the interventricular septum of three open-chest swine hearts. The properties of the myocardial contraction response of the septum were compared between normal and acute ischemic conditions, where the acute ischemic condition of the septum originated from direct avascularization of the left anterior descending (LAD) coronary artery. The result showed that the contraction response propagated from the basal side to the apical side along the septum. The estimated propagation velocities in the normal and acute ischemic conditions were 3.6 and 1.9 m/s, respectively. This finding indicates that acute ischemia which occurred 5 s after the avascularization of the LAD promptly suppressed the propagation velocity through the ventricular septum to about half the normal velocity. It was suggested that the myocardial ischemic region could be identified using the difference in the propagation velocity of the myocardial response to contraction.

  3. Image-assisted non-invasive and dynamic biomechanical analysis of human joints.

    PubMed

    Muhit, Abdullah A; Pickering, Mark R; Scarvell, Jennifer M; Ward, Tom; Smith, Paul N

    2013-07-07

    Kinematic analysis provides a strong link between musculoskeletal injuries, chronic joint conditions, treatment planning/monitoring and prosthesis design/outcome. However, fast and accurate 3D kinematic analysis still remains a challenge in order to translate this procedure into clinical scenarios. 3D computed tomography (CT) to 2D single-plane fluoroscopy registration is a promising non-invasive technology for biomechanical examination of human joints. Although this technique has proven to be very precise in terms of in-plane translation and rotation measurements, out-of-plane motion estimations have been a difficulty so far. Therefore, to enable this technology into clinical translation, precise and fast estimation of both in-plane and out-of-plane movements is crucial, which is the aim of this paper. Here, a fast and accurate 3D/2D registration technique is proposed to evaluate biomechanical/kinematic analysis. The proposed algorithm utilizes a new multi-modal similarity measure called 'sum of conditional variances', a coarse-to-fine Laplacian of Gaussian filtering approach for robust gradient-descent optimization and a novel technique for the analytic calculation of the required gradients for out-of-plane rotations. Computer simulations and in vitro experiments showed that the new approach was robust in terms of the capture range, required significantly less iterations to converge and achieved good registration and kinematic accuracy when compared to existing techniques and to the 'gold-standard' Roentgen stereo analysis.

  4. Non-invasive cardiac pacing with image-guided focused ultrasound

    NASA Astrophysics Data System (ADS)

    Marquet, Fabrice; Bour, Pierre; Vaillant, Fanny; Amraoui, Sana; Dubois, Rémi; Ritter, Philippe; Haïssaguerre, Michel; Hocini, Mélèze; Bernus, Olivier; Quesson, Bruno

    2016-11-01

    Currently, no non-invasive cardiac pacing device acceptable for prolonged use in conscious patients exists. High Intensity Focused Ultrasound (HIFU) can be used to perform remote pacing using reversibility of electromechanical coupling of cardiomyocytes. Here we described an extracorporeal cardiac stimulation device and study its efficacy and safety. We conducted experiments ex vivo and in vivo in a large animal model (pig) to evaluate clinical potential of such a technique. The stimulation threshold was determined in 10 different ex vivo hearts and different clinically relevant electrical effects such as consecutive stimulations of different heart chambers with a single ultrasonic probe, continuous pacing or the inducibility of ventricular tachycardia were shown. Using ultrasonic contrast agent, consistent cardiac stimulation was achievable in vivo for up to 1 hour sessions in 4 different animals. No damage was observed in inversion-recovery MR sequences performed in vivo in the 4 animals. Histological analysis revealed no differences between stimulated and control regions, for all ex vivo and in vivo cases.

  5. Non-invasive cardiac pacing with image-guided focused ultrasound

    PubMed Central

    Marquet, Fabrice; Bour, Pierre; Vaillant, Fanny; Amraoui, Sana; Dubois, Rémi; Ritter, Philippe; Haïssaguerre, Michel; Hocini, Mélèze; Bernus, Olivier; Quesson, Bruno

    2016-01-01

    Currently, no non-invasive cardiac pacing device acceptable for prolonged use in conscious patients exists. High Intensity Focused Ultrasound (HIFU) can be used to perform remote pacing using reversibility of electromechanical coupling of cardiomyocytes. Here we described an extracorporeal cardiac stimulation device and study its efficacy and safety. We conducted experiments ex vivo and in vivo in a large animal model (pig) to evaluate clinical potential of such a technique. The stimulation threshold was determined in 10 different ex vivo hearts and different clinically relevant electrical effects such as consecutive stimulations of different heart chambers with a single ultrasonic probe, continuous pacing or the inducibility of ventricular tachycardia were shown. Using ultrasonic contrast agent, consistent cardiac stimulation was achievable in vivo for up to 1 hour sessions in 4 different animals. No damage was observed in inversion-recovery MR sequences performed in vivo in the 4 animals. Histological analysis revealed no differences between stimulated and control regions, for all ex vivo and in vivo cases. PMID:27827415

  6. Non-invasive red light optogenetic pacing and optical coherence microscopy (OCM) imaging for drosophila melanogaster (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Men, Jing; Li, Airong; Jerwick, Jason; Tanzi, Rudolph E.; Zhou, Chao

    2017-02-01

    Cardiac pacing could be a powerful tool for investigating mammalian cardiac electrical conduction systems as well as for treatment of certain cardiac pathologies. However, traditional electrical pacing using pacemaker requires an invasive surgical procedure. Electrical currents from the implanted electrodes can also cause damage to heart tissue, further restricting its utility. Optogenetic pacing has been developed as a promising, non-invasive alternative to electrical stimulation for controlling animal heart rhythms. It induces heart contractions by shining pulsed light on transgene-generated microbial opsins, which in turn activate the light gated ion channels in animal hearts. However, commonly used opsins in optogenetic pacing, such as channelrhodopsin-2 (ChR2), require short light wavelength stimulation (475 nm), which is strongly absorbed and scattered by tissue. Here, we performed optogenetic pacing by expression of recently engineered red-shifted microbial opsins, ReaChR and CsChrimson, in a well-established animal model, Drosophila melanogaster, using the 617 nm stimulation light pulses. The OCM technique enables non-invasive optical imaging of animal hearts with high speed and ultrahigh axial and transverse resolutions. We integrated a customized OCM system with the optical stimulation system to monitor the optogenetic pacing noninvasively. The use of red-sifted opsins enabled deeper penetration of simulating light at lower power, which is promising for applications of optogenetic pacing in mammalian cardiac pathology studies or clinical treatments in the future.

  7. Non-invasive in vivo imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin.

    PubMed

    Kramer, Lovro; Renko, Miha; Završnik, Janja; Turk, Dušan; Seeger, Markus A; Vasiljeva, Olga; Grütter, Markus G; Turk, Vito; Turk, Boris

    2017-01-01

    Cysteine cathepsins often contribute to cancer progression due to their overexpression in the tumour microenvironment and therefore present attractive targets for non-invasive diagnostic imaging. However, the development of highly selective and versatile small molecule probes for cathepsins has been challenging. Here, we targeted tumour-associated cathepsin B using designed ankyrin repeat proteins (DARPins). The selective DARPin 8h6 inhibited cathepsin B with picomolar affinity (Ki = 35 pM) by binding to a site with low structural conservation in cathepsins, as revealed by the X-ray structure of the complex. DARPin 8h6 blocked cathepsin B activity in tumours ex vivo and was successfully applied in in vivo optical imaging in two mouse breast cancer models, in which cathepsin B was bound to the cell membrane or secreted to the extracellular milieu by tumour and stromal cells. Our approach validates cathepsin B as a promising diagnostic and theranostic target in cancer and other inflammation-associated diseases.

  8. Human skeletal muscle architecture studied in vivo by non-invasive imaging techniques: functional significance and applications.

    PubMed

    Narici, M

    1999-04-01

    The internal architecture plays an essential role in determining the functional features of skeletal muscle. Both length-force and force-velocity relationships depend on the spatial arrangement of muscle fibres in skeletal muscle. The degree of muscle pennation determines both the amount of contractile tissue packed along the tendons and fibre length, and is reflected by the force-generating capacity and shortening velocity of the muscle and by the elastic properties of the muscle-tendon complex. Until recently, knowledge on human muscle architecture was based on measurements performed on cadavers, whose muscle fibres were often shrunk by the preserving medium and by age. With the introduction of non-invasive imaging techniques, it has become possible to study muscle architecture in vivo at rest and the changes thereof upon contraction. This paper discusses the applications of these techniques, namely ultrasonography and nuclear magnetic resonance imaging, and their relevance in physiology and biomechanics.

  9. A General Approach to the Non-Invasive Imaging of Transgenes Using Cis-Linked Herpes Simplex Virus Thymidine Kinase1

    PubMed Central

    Tjuvajev, Juri G; Joshi, Arjun; Callegari, James; Lindsley, Laura; Joshi, Revathi; Balatoni, Julius; Finn, Ronald; Larson, Steven M; Sadelain, Michel; Blasberg, Ronald G

    1999-01-01

    Abstract Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression and imaging of HSV1-tk (a marker gene) can be used to monitor the expression of the LacZ gene (a second gene) under the transcriptional control of a single promoter within a bicistronic unit that includes a type II internal ribosomal entry site. In cells bearing a single copy of the vector, the expression of the two genes is proportional and constant, both in vitro and in vivo. We demonstrate that non-invasive imaging of HSV1-tk gene accurately reflects the topology and activity of the other cis-linked transgene. PMID:10935486

  10. Non-invasive Measurement of Thermal Diffusivity Using High-Intensity Focused Ultrasound and Through-Transmission Ultrasonic Imaging.

    PubMed

    Yeshurun, Lilach; Azhari, Haim

    2016-01-01

    Thermal diffusivity at the site ablated by high-intensity focused ultrasound (HIFU) plays an important role in the final therapeutic outcome, as it influences the temperature's spatial and temporal distribution. Moreover, as tissue thermal diffusivity is different in tumors as compared with normal tissue, it could also potentially be used as a new source of imaging contrast. The aim of this study was to examine the feasibility of combining through-transmission ultrasonic imaging and HIFU to estimate thermal diffusivity non-invasively. The concept was initially evaluated using a computer simulation. Then it was experimentally tested on phantoms made of agar and ex vivo porcine fat. A computerized imaging system combined with a HIFU system was used to heat the phantoms to temperatures below 42°C to avoid irreversible damage. Through-transmission scanning provided the time-of-flight values in a region of interest during its cooling process. The time-of-flight values were consequently converted into mean values of speed of sound. Using the speed-of-sound profiles along with the developed model, we estimated the changes in temperature profiles over time. These changes in temperature profiles were then used to calculate the corresponding thermal diffusivity of the studied specimen. Thermal diffusivity for porcine fat was found to be lower by one order of magnitude than that obtained for agar (0.313×10(-7)m(2)/s vs. 4.83×10(-7)m(2)/s, respectively, p < 0.041). The fact that there is a substantial difference between agar and fat implies that non-invasive all-ultrasound thermal diffusivity mapping is feasible. The suggested method may particularly be suitable for breast scanning. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  11. [Markers for non-invasive molecular genetic diagnosis of oncourological diseases].

    PubMed

    Mikhaĭlenko, D S; Perepechin, D V; Apolikhin, O I; Efremov, G D; Sivkov, A V

    2014-01-01

    Currently, there is accumulated mass of data on the molecular-genetic disorders in prostate cancer (PCa), bladder cancer (BC) and renal cancer (RC). Tumor cells in these diseases are present in the urine sediment; their number is sufficient for molecular genetic analysis that makes possible the development of noninvasive diagnosis of oncourological diseases. A characteristic feature of PCa includes the overexpression of the PCA3 gene; assay kit Progensa™ to quantify such overexpression has been developed; approximately 50% of tumors express a TMPRSS2-ERG chimeric oncogene. Combined analysis of PCA3 and TMPRSS2-ERG allows to detect PCa with a diagnostic accuracy of 84%, which is significantly higher than that of prostate specific antigen test. As a potential markers of BC, there are somatic mutations in FGFR3, PIK3CA, TERT genes in urine sediment, which are found in this disease with a frequency of about 60, 30 and 50%, respectively. The basis of the test system for DNA diagnosis of BC in urine sediment may include a definition of a combination of mutations in these genes with microsatellite instability. Aberrant methylation of the 5'-regulatory regions of tumor suppressor genes, integrated in the panel, also is considered as a tool in the diagnosis of RC (VHL, RASSF1, RARB2, CDH1), PCa (GSTP1, PTGS2, LGALS3) and BC (RASSF1, APC, SFRP2) after standardization of panels of loci investigated, sample preparation methods, bisulfite conversion, and the design of primers and probes. Thus, a test systems for molecular genetic diagnosis of oncourological diseases in urine sediment are currently available or may be developed in the near future.

  12. Non-invasive genetic sampling for molecular sexing and microsatellite genotyping of hyacinth macaw (Anodorhynchus hyacinthinus).

    PubMed

    Presti, Flavia T; Meyer, Janaína; Antas, Paulo T Z; Guedes, Neiva M R; Miyaki, Cristina Y

    2013-03-01

    Molted feather sampling is a useful tool for genetic analyses of endangered species, but it is often very laborious due to the low quality and quantity of the DNA obtained. In the present study we show the parts of feathers that resulted in better yield of DNA. In descending order these were: blood clot outside the umbilicus, umbilicus (without blood clot), tip, inner membrane, and small calamus. Compared to DNA extracted from blood samples, DNA extracted from feathers produced microsatellite alleles of poorer quality and had to be processed immediately after extraction. As expected due to the level of DNA degradation, molecular sexing protocols that result in shorter PCR products were more efficient.

  13. In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Artzi, Natalie; Oliva, Nuria; Puron, Cristina; Shitreet, Sagi; Artzi, Shay; Bon Ramos, Adriana; Groothuis, Adam; Sahagian, Gary; Edelman, Elazer R.

    2011-09-01

    The design of erodible biomaterials relies on the ability to program the in vivo retention time, which necessitates real-time monitoring of erosion. However, in vivo performance cannot always be predicted by traditional determination of in vitro erosion, and standard methods sacrifice samples or animals, preventing sequential measures of the same specimen. We harnessed non-invasive fluorescence imaging to sequentially follow in vivo material-mass loss to model the degradation of materials hydrolytically (PEG:dextran hydrogel) and enzymatically (collagen). Hydrogel erosion rates in vivo and in vitro correlated, enabling the prediction of in vivo erosion of new material formulations from in vitro data. Collagen in vivo erosion was used to infer physiologic in vitro conditions that mimic erosive in vivo environments. This approach enables rapid in vitro screening of materials, and can be extended to simultaneously determine drug release and material erosion from a drug-eluting scaffold, or cell viability and material fate in tissue-engineering formulations.

  14. Capsaicin-induced mucus secretion in rat airways assessed in vivo and non-invasively by magnetic resonance imaging

    PubMed Central

    Karmouty-Quintana, H; Cannet, C; Sugar, R; Fozard, J R; Page, C P; Beckmann, N

    2007-01-01

    Background and purpose: An up-regulation of the sensory neural pathways in the lung has been implicated in asthma and chronic obstructive pulmonary disease (COPD) and is thought to contribute to mucus hypersecretion, an essential feature of both diseases. The aim of this study was to assess non-invasively the acute effects (up to 60 min) of sensory nerve stimulation by capsaicin in the lung, using magnetic resonance imaging (MRI). Experimental approach: Male Brown Norway rats were imaged prior to and 10, 30 and 60 min after intra-tracheal challenge with capsaicin (30 μgkg−1) or vehicle (0.5% ethanol solution). In subsequent studies, pre-treatment with the transient receptor potential vanilloid (TRPV)-1 antagonist, capsazepine; the dual neurokinin (NK) 1 and NK2 receptor antagonist, DNK333 and the mast cell stabilizer, di-sodium cromoglycate (DSCG) was used to modulate the effects of capsaicin. Key results: Diffuse fluid signals were detected by MRI in the lung as early as 10 min after capsaicin, remaining constant 30 and 60 min after treatment. Broncho-alveolar lavage (BAL) fluid analysis performed 60 min after capsaicin revealed increased mucin concentration. Capsazepine (3.5 mgkg−1), DNK333 (10 mgkg−1) but not DSCG (10 mgkg−1) administered prophylactically were able to block the effect of capsaicin in the airways. Conclusions and implications: These observations suggest that the fluid signals detected by MRI after capsaicin administration reflected predominantly the release of mucus following activation of sensory nerves. They point to the opportunity of non-invasively assessing with MRI the influence of neuronal mechanisms in animal models of asthma and COPD. PMID:17351665

  15. Non-invasive genetic sampling for molecular sexing and microsatellite genotyping of hyacinth macaw (Anodorhynchus hyacinthinus)

    PubMed Central

    Presti, Flavia T.; Meyer, Janaína; Antas, Paulo T.Z.; Guedes, Neiva M.R.; Miyaki, Cristina Y.

    2013-01-01

    Molted feather sampling is a useful tool for genetic analyses of endangered species, but it is often very laborious due to the low quality and quantity of the DNA obtained. In the present study we show the parts of feathers that resulted in better yield of DNA. In descending order these were: blood clot outside the umbilicus, umbilicus (without blood clot), tip, inner membrane, and small calamus. Compared to DNA extracted from blood samples, DNA extracted from feathers produced microsatellite alleles of poorer quality and had to be processed immediately after extraction. As expected due to the level of DNA degradation, molecular sexing protocols that result in shorter PCR products were more efficient. PMID:23569419

  16. Non-Invasive Breast Cancer Diagnosis through Electrochemical Biosensing at Different Molecular Levels.

    PubMed

    Campuzano, Susana; Pedrero, María; Pingarrón, José Manuel

    2017-08-31

    The rapid and accurate determination of specific circulating biomarkers at different molecular levels with non- or minimally invasive methods constitutes a major challenge to improve the breast cancer outcomes and life quality of patients. In this field, electrochemical biosensors have demonstrated to be promising alternatives against more complex conventional strategies to perform fast, accurate and on-site determination of circulating biomarkers at low concentrations in minimally treated body fluids. In this article, after discussing briefly the relevance and current challenges associated with the determination of breast cancer circulating biomarkers, an updated overview of the electrochemical affinity biosensing strategies emerged in the last 5 years for this purpose is provided highlighting the great potentiality of these methodologies. After critically discussing the most interesting features of the electrochemical strategies reported so far for the single or multiplexed determination of such biomarkers with demonstrated applicability in liquid biopsy analysis, existing challenges still to be addressed and future directions in this field will be pointed out.

  17. Analysis of microparticle penetration into human and porcine skin: non-invasive imaging with multiphoton excitation microscopy

    NASA Astrophysics Data System (ADS)

    Mulholland, William J.; Kendall, Mark A.; Bellhouse, Brian J.; White, Nick

    2002-06-01

    At the University of Oxford and PowderJect Pharmaceuticals plc, a unique form of needle-free injection technology has been developed. Powdered vaccines and drugs in micro-particle form are accelerated in a high-speed gas flow to sufficient velocity to enter the skin, subsequently achieving a pharmaceutical effect. To optimize the delivery of vaccines and drugs with this method a detailed understanding of the interactive processes that occur between the microparticles and the skin is necessary. Investigations to date of micro-particle delivery into excised human and animal tissue have involved image analyses of histology sections. In the present study, a series of investigations were conducted on excised human and porcine skin using the technique of Multi-Photon fluorescence excitation Microscopy (MPM) to image particles and skin structures post-penetration. Micro-particles of various size and composition were imaged with infrared laser excitation. Three-dimensional images of stratum corneum and epidermal cell deformation due to micro-particle penetration were obtained. Measurements of micro-particle penetration depth taken from z-scan image stacks were used to successfully quantify micro-particle distribution within the skin, without invasively disrupting the skin target. This study has shown that MPM has great potential for the non-invasive imaging of particle skin interactive processes that occur with the transdermal delivery of powdered micro-particle vaccines and drugs.

  18. Non-Invasive Breast Cancer Diagnosis through Electrochemical Biosensing at Different Molecular Levels

    PubMed Central

    Campuzano, Susana

    2017-01-01

    The rapid and accurate determination of specific circulating biomarkers at different molecular levels with non- or minimally invasive methods constitutes a major challenge to improve the breast cancer outcomes and life quality of patients. In this field, electrochemical biosensors have demonstrated to be promising alternatives against more complex conventional strategies to perform fast, accurate and on-site determination of circulating biomarkers at low concentrations in minimally treated body fluids. In this article, after discussing briefly the relevance and current challenges associated with the determination of breast cancer circulating biomarkers, an updated overview of the electrochemical affinity biosensing strategies emerged in the last 5 years for this purpose is provided highlighting the great potentiality of these methodologies. After critically discussing the most interesting features of the electrochemical strategies reported so far for the single or multiplexed determination of such biomarkers with demonstrated applicability in liquid biopsy analysis, existing challenges still to be addressed and future directions in this field will be pointed out. PMID:28858236

  19. Near-infrared quantum-dot-based non-invasive in vivo imaging of squamous cell carcinoma U14

    NASA Astrophysics Data System (ADS)

    Cao, Yu'an; Yang, Kai; Li, Zhigang; Zhao, Cheng; Shi, Chunmeng; Yang, Jia

    2010-11-01

    Near-infrared (near-ir) quantum dots (QDs) are well known for their excellent optical characteristics. They hold great potential for applications in non-invasive long term observation and tracing of cells in vivo. Here, near-ir QDs with an emission wavelength of 800 nm (QD800) were used to label squamous cell carcinoma cell line U14 (U14/QD800). The effect of tissue depth and animal fur on the imaging sensitivity and stability was evaluated following subcutaneous and intramuscular injection into Kunming mice, employing an in vivo imaging system. We have demonstrated that QD800-based visual in vivo imaging increased the sensitivity of cancer early detection by a factor of 100 compared with traditional detection methods. More importantly, this study proved for the first time that animal fur has a serious impact on the detection sensitivity and duration of QD-based in vivo imaging. In general, the duration and sensitivity of QD800 for in vivo imaging were not greatly affected by a depth less than 1.8 ± 0.21 mm (subcutaneous or intramuscular). This study provides critical reference data for further research on near-ir QD-based early detection and in vivo visual observation of cancer.

  20. Clinical application of a molecular assay for the detection of dermatophytosis and a novel non-invasive sampling technique.

    PubMed

    Kizny Gordon, Alice; McIver, Christopher; Kim, Minhee; Murrell, Dedee F; Taylor, Peter

    2016-12-01

    The dermatophytoses are the most common superficial fungal infections worldwide. Clinical diagnosis is not reliable as there are many differentials, and laboratory diagnosis is required to gain access to treatment in more severe disease. Traditional diagnostic methods are limited by suboptimal sensitivity, specificity and prolonged turnaround times. Molecular methods are being used increasingly in the diagnostic algorithm in the clinical microbiology laboratory. The aim of this study was to evaluate a real-time polymerase chain reaction (RT-PCR) targeting the chitin synthase 1 gene (CHS1) of dermatophytes for analytical specificity, and to assess its clinical application by comparing it to the current methods of microscopy and culture. We also assessed a novel non-invasive sample collection technique involving adhesive tape impressions of suspected lesions. The PCR was highly specific, being able to discern between cultures of dermatophytes and other microorganisms. It also proved to be more sensitive than traditional methods at detecting dermatophytes in clinical samples. Similar sensitivities were seen on the samples assessed by the adhesive tape technique. An internal control system allowed for the detection of inhibition in certain culture and clinical specimens. This rapid and cost-effective technique could be incorporated into the initial diagnostic algorithm for dermatophytosis in Australian laboratories. Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  1. Non-invasive imaging of breast cancer with diffusing near-infrared light

    NASA Astrophysics Data System (ADS)

    Konecky, Soren D.

    Diffuse optical tomography (DOT) is a new medical imaging technique that combines biomedical optics with the principles of computed tomography. We use DOT to quantitatively reconstruct images of complex phantoms with millimeter sized features located centimeters deep within a highly-scattering medium. A non-contact instrument is employed to collect large data sets consisting of greater than 107 source-detector pairs. Images are reconstructed using a fast image reconstruction algorithm based on an analytic solution to the inverse scattering problem for diffuse light. We also describe a next generation DOT breast imaging device for frequency domain transmission data acquisition in the parallel plate geometry. Frequency domain heterodyne measurements are made by intensity modulating a continuous wave laser source with an electro-optic modulator (EOM) and detecting the transmitted light with a gain-modulated image intensifier coupled to a CCD. Finally, we acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using DOT and Positron Emission Tomography (PET). Co-registration of DOT and PET images is facilitated by a mutual information maximization algorithm. We also compare DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations are found between both total hemoglobin concentration and tissue scattering, and fluorodeoxyglucose (18F-FDG) uptake.

  2. Non-invasive imaging and monitoring of rodent retina using simultaneous dual-band optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Cimalla, Peter; Burkhardt, Anke; Walther, Julia; Hoefer, Aline; Wittig, Dierk; Funk, Richard; Koch, Edmund

    2011-03-01

    Spectral domain dual-band optical coherence tomography for simultaneous imaging of rodent retina in the 0.8 μm and 1.3 μm wavelength region and non-invasive monitoring of the posterior eye microstructure in the field of retinal degeneration research is demonstrated. The system is illuminated by a supercontinuum laser source and allows three-dimensional imaging with high axial resolution better than 3.8 μm and 5.3 μm in tissue at 800 nm and 1250 nm, respectively, for precise retinal thickness measurements. A fan-shaped scanning pattern with the pivot point close to the eye's pupil and a contact lens are applied to obtain optical access to the eye's fundus. First in vivo experiments in a RCS (royal college of surgeons) rat model with gene-related degeneration of the photoreceptor cells show good visibility of the retinal microstructure with sufficient contrast for thickness measurement of individual retinal layers. An enhanced penetration depth at 1250 nm is clearly identifiable revealing sub-choroidal structures that are not visible at 800 nm. Furthermore, additional simultaneous imaging at 1250 nm improves image quality by frequency compounding speckle noise reduction. These results are encouraging for time course studies of the rodent retina concerning its development related to disease progression and treatment response.

  3. Multimodal Imaging and Spectroscopy Fiber-bundle Microendoscopy Platform for Non-invasive, In Vivo Tissue Analysis.

    PubMed

    Greening, Gage J; Rajaram, Narasimhan; Muldoon, Timothy J

    2016-10-17

    Recent fiber-bundle microendoscopy techniques enable non-invasive analysis of in vivo tissue using either imaging techniques or a combination of spectroscopy techniques. Combining imaging and spectroscopy techniques into a single optical probe may provide a more complete analysis of tissue health. In this article, two dissimilar modalities are combined, high-resolution fluorescence microendoscopy imaging and diffuse reflectance spectroscopy, into a single optical probe. High-resolution fluorescence microendoscopy imaging is a technique used to visualize apical tissue micro-architecture and, although mostly a qualitative technique, has demonstrated effective real-time differentiation between neoplastic and non-neoplastic tissue. Diffuse reflectance spectroscopy is a technique which can extract tissue physiological parameters including local hemoglobin concentration, melanin concentration, and oxygen saturation. This article describes the specifications required to construct the fiber-optic probe, how to build the instrumentation, and then demonstrates the technique on in vivo human skin. This work revealed that tissue micro-architecture, specifically apical skin keratinocytes, can be co-registered with its associated physiological parameters. The instrumentation and fiber-bundle probe presented here can be optimized as either a handheld or endoscopically-compatible device for use in a variety of organ systems. Additional clinical research is needed to test the viability of this technique for different epithelial disease states.

  4. Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities.

    PubMed

    Bertoglio, Daniele; Verhaeghe, Jeroen; Santermans, Eva; Amhaoul, Halima; Jonckers, Elisabeth; Wyffels, Leonie; Van Der Linden, Annemie; Hens, Niel; Staelens, Steven; Dedeurwaerdere, Stefanie

    2017-03-01

    Brain inflammation is an important factor in the conversion of a healthy brain into an epileptic one, a phenomenon known as epileptogenesis, offering a new entry point for prognostic tools. The development of anti-epileptogenic therapies to treat before or at disease onset is hampered by our inability to predict the severity of the disease outcome. In a rat model of temporal lobe epilepsy we aimed to assess whether in vivo non-invasive imaging of brain inflammation at disease onset was predictive of spontaneous recurrent seizures (SRS) frequency and severity of depression-like and sensorimotor-related comorbidities. To this end, translocator protein, a biomarker of inflammation, was imaged by means of positron emission tomography (PET) 2 and 4weeks post-status epilepticus using [(18)F]-PBR111. Translocator protein was highly upregulated 2weeks post-status epilepticus in limbic structures (up to 2.1-fold increase compared to controls in temporal lobe, P<0.001), whereas 4weeks post-status epilepticus, upregulation decreased (up to 1.6-fold increase compared to controls in temporal lobe, P<0.01) and was only apparent in a subset of these regions. Animals were monitored with video-electroencephalography during all stages of disease (acute, latent - first seizures appearing around 2weeks post-status epilepticus - and chronic phases), for a total of 12weeks, in order to determine SRS frequency for each subject (range 0.00-0.83SRS/day). We found that regional PET uptake at 2 and 4weeks post-status epilepticus correlated with the severity of depression-like and sensorimotor-related comorbidities during chronic epilepsy (P<0.05 for each test). Regional PET imaging did not correlate with SRS frequency, however, by applying a multivariate data-driven modeling approach based on translocator protein PET imaging at 2weeks post-status epilepticus, we accurately predicted the frequency of SRS (R=0.92; R(2)=0.86; P<0.0001) at the onset of epilepsy. This study not only demonstrates

  5. Multispectral imaging approach for simplified non-invasive in-vivo evaluation of gingival erythema

    NASA Astrophysics Data System (ADS)

    Eckhard, Timo; Valero, Eva M.; Nieves, Juan L.; Gallegos-Rueda, José M.; Mesa, Francisco

    2012-03-01

    Erythema is a common visual sign of gingivitis. In this work, a new and simple low-cost image capture and analysis method for erythema assessment is proposed. The method is based on digital still images of gingivae and applied on a pixel-by-pixel basis. Multispectral images are acquired with a conventional digital camera and multiplexed LED illumination panels at 460nm and 630nm peak wavelength. An automatic work-flow segments teeth from gingiva regions in the images and creates a map of local blood oxygenation levels, which relates to the presence of erythema. The map is computed from the ratio of the two spectral images. An advantage of the proposed approach is that the whole process is easy to manage by dental health care professionals in clinical environment.

  6. Imaging-Based Methods for Non-invasive Assessment of Bone Properties Influenced by Mechanical Loading.

    PubMed

    Macintyre, Norma J; Lorbergs, Amanda L

    2012-01-01

    Purpose: To describe the most common in vivo imaging-based research tools used to assess bone properties that are influenced by mechanical loading associated with exercise, habitual physical activity, or disease states. Bone is a complex metabolically active tissue that adapts to changes in mechanical loading by altering the amount and spatial organization of mineral. Method: Using a narrative review design, the authors provide an overview of bone biology and biomechanics to emphasize the importance of bone size scale, porosity, and degree of mineralization when interpreting measures acquired using quantitative ultrasound (QUS), dual-energy X-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI), and finite element analysis (FEA). For each imaging modality, basic imaging principles, typical outcome measures associated with changes in mechanical loading, and salient features for physiotherapists are described. Main Results: While each imaging modality has strengths and limitations, currently CT-based methods are best suited for determining the effects of mechanical loading on bone properties—particularly in the peripheral skeleton. Conclusions: Regardless of the imaging technology used, the physiotherapist must carefully consider the assumptions of the imaging-based method, the clinical context, the nature of the change in mechanical loading, and the expected time course for change in bone properties.

  7. New trends in imaging spectroscopy: the non-invasive study of the Scrovegni Chapel stained glass windows

    NASA Astrophysics Data System (ADS)

    Rebollo, E.; Ratti, F.; Cortelazzo, G. M.; Poletto, L.; Bertoncello, R.

    2011-06-01

    Imaging spectroscopy (IS) extends the measurement of one-dimensional UV-VIS-NIR spectroscopy to two-dimensional domain providing material characterization and localization. The technique is gaining importance for the study of cultural heritage but its application is mainly focused on the analysis of pigments in paintings. An IS device has been developed and then applied to the study of chromophores in glassy objects. It consists of a visible imaging spectrograph, mounted on a rotation stage, which captures monochromatic images of the sample within a wavelength range from 420 nm to 850 nm. The system has been used for the characterization and mapping of chromophores of hundreds of coloured glass tesserae of the stained glass windows from the Scrovegni Chapel (Padua, Italy). Two measurement methodologies have been performed: transmission and double-transmission modes. In the first case, lamps used to illuminate the sample and the spectrograph are placed on the opposite side of the window, to acquire directly the signal transmitted from the glass. In the latter case, the lamps and the spectrograph are placed on the same side of the window, that is placed on a white scattering screen. The acquired signal comes from the light of the lamps transmitted through the glass, then diffused back by the opaque white screen and finally transmitted again through the glass. Results are discussed comparing both modalities in terms of signal-to-noise ratio and spectral contrast. Visible spectra acquired allow the clear identification of several chromophores, e.g. Co(II), Cr(III) or Mn(III). The IS device acquires numerous spectra in relatively short time in a non-invasive way. According to the authors knowledge, this is the first time in which visible imaging spectroscopy technique has been applied for the study of stained glass windows. As the results show, it could represent a powerful and innovative tool to map chromophores of this kind of artefact, particularly when integrated

  8. Non-Invasive Imaging for Congenital Heart Disease: Recent Innovations in Transthoracic Echocardiography

    PubMed Central

    Koestenberger, Martin; Friedberg, Mark K.; Ravekes, William; Nestaas, Eirik; Hansmann, Georg

    2013-01-01

    Transthoracic echocardiography (TTE) is an important tool for diagnosis and follow-up of patients with congenital heart disease (CHD). Appropriate use of TTE can reduce the need for more invasive and complex modalities, such as cardiac catheterization and cardiac magnetic resonance imaging. New echocardiographic techniques have emerged for the assessment of ventricular systolic and diastolic function: Tissue Doppler imaging, tissue tracking, strain and strain rate imaging, vector velocity imaging (VVI), myocardial performance index, myocardial acceleration during isovolumic contraction (IVA), the ratio of systolic to diastolic duration (S/D ratio), and other measurements of systolic right ventricular (RV) function like tricuspid annular plane systolic excursion (TAPSE). These modalities may become valuable indicators of ventricular performance, compliance and disease progression, with the caveat of preload-dependency of the variables measured. In addition, three-dimensional (3D) echocardiography for the assessment of cardiac anatomy, valvular function, device position, ventricular volumes and ejection fraction is integrated into routine clinical care. In this review, we discuss the potential use and limitations of these new echocardiographic techniques in patients with CHD. A particular focus is on the echocardiographic assessment of right ventricular (RV) function by means of tissue Doppler imaging, tissue tracking, and three-dimensional imaging, in conditions associated with increased right ventricular volume or pressure load. PMID:24163784

  9. In vivo photothermal optical coherence tomography for non-invasive imaging of endogenous absorption agents.

    PubMed

    Makita, Shuichi; Yasuno, Yoshiaki

    2015-05-01

    In vivo photothermal optical coherence tomography (OCT) is demonstrated for cross-sectional imaging of endogenous absorption agents. In order to compromise the sensitivity, imaging speed, and sample motion immunity, a new photothermal detection scheme and phase processing method are developed. Phase-resolved swept-source OCT and fiber-pigtailed laser diode (providing excitation at 406 nm) are combined to construct a high-sensitivity photothermal OCT system. OCT probe and excitation beam coaxially illuminate and are focused on tissues. The photothermal excitation and detection procedure is designed to obtain high efficiency of photothermal effect measurement. The principle and method of depth-resolved cross-sectional imaging of absorption agents with photothermal OCT has been derived. The phase-resolved thermal expansion detection algorithm without motion artifact enables in vivo detection of photothermal effect. Phantom imaging with a blood phantom and in vivo human skin imaging are conducted. A phantom with guinea-pig blood as absorber has been scanned by the photothermal OCT system to prove the concept of cross-sectional absorption agent imaging. An in vivo human skin measurement is also performed with endogenous absorption agents.

  10. In vivo photothermal optical coherence tomography for non-invasive imaging of endogenous absorption agents

    PubMed Central

    Makita, Shuichi; Yasuno, Yoshiaki

    2015-01-01

    In vivo photothermal optical coherence tomography (OCT) is demonstrated for cross-sectional imaging of endogenous absorption agents. In order to compromise the sensitivity, imaging speed, and sample motion immunity, a new photothermal detection scheme and phase processing method are developed. Phase-resolved swept-source OCT and fiber-pigtailed laser diode (providing excitation at 406 nm) are combined to construct a high-sensitivity photothermal OCT system. OCT probe and excitation beam coaxially illuminate and are focused on tissues. The photothermal excitation and detection procedure is designed to obtain high efficiency of photothermal effect measurement. The principle and method of depth-resolved cross-sectional imaging of absorption agents with photothermal OCT has been derived. The phase-resolved thermal expansion detection algorithm without motion artifact enables in vivo detection of photothermal effect. Phantom imaging with a blood phantom and in vivo human skin imaging are conducted. A phantom with guinea-pig blood as absorber has been scanned by the photothermal OCT system to prove the concept of cross-sectional absorption agent imaging. An in vivo human skin measurement is also performed with endogenous absorption agents. PMID:26137374

  11. Multiphoton laser tomography and fluorescence lifetime imaging of basal cell carcinoma: morphologic features for non-invasive diagnostics.

    PubMed

    Seidenari, Stefania; Arginelli, Federica; Dunsby, Christopher; French, Paul; König, Karsten; Magnoni, Cristina; Manfredini, Marco; Talbot, Clifford; Ponti, Giovanni

    2012-11-01

    Multiphoton laser tomography (MPT) combined with fluorescence lifetime imaging (FLIM) is a non-invasive imaging technique, which gives access to the cellular and extracellular morphology of the skin. The aim of our study was to assess the sensitivity and specificity of MPT/FLIM descriptors for basal cell carcinoma (BCC), to improve BCC diagnosis and the identification of tumor margins. In the preliminary study, FLIM images referring to 35 BCCs and 35 healthy skin samples were evaluated for the identification of morphologic descriptors characteristic of BCC. In the main study, the selected parameters were blindly evaluated on a test set comprising 63 BCCs, 63 healthy skin samples and 66 skin lesions. Moreover, FLIM values inside a region of interest were calculated on 98 healthy skin and 98 BCC samples. In the preliminary study, three epidermal descriptors and 7 BCC descriptors were identified. The specificity of the diagnostic criteria versus 'other lesions' was extremely high, indicating that the presence of at least one BCC descriptor makes the diagnosis of 'other lesion' extremely unlikely. FLIM values referring to BCC cells significantly differed from those of healthy skin. In this study, we identified morphological and numerical descriptors enabling the differentiation of BCC from other skin disorders and its distinction from healthy skin in ex vivo samples. In future, MPT/FLIM may be applied to skin lesions to provide direct clinical guidance before biopsy and histological examination and for the identification of tumor margins allowing a complete surgical removal.

  12. Non-invasive imaging techniques in assessing non-alcoholic fatty liver disease: a current status of available methods

    PubMed Central

    Lăpădat, AM; Jianu, IR; Ungureanu, BS; Florescu, LM; Gheonea, DI; Sovaila, S; Gheonea, IA

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an ailment affecting and increasing a number of people worldwide diagnosed via non-invasive imaging techniques, at a time when a minimum harm caused by medical procedures is rightfully emphasized, more sought after, than ever before. Liver steatosis should not be taken lightly even if its evolution is largely benign as it has the potential to develop into non-alcoholic steatohepatitis (NASH) or even more concerning, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Traditionally, liver biopsy has been the standard for diagnosing this particular liver disease, but nowadays, a consistent number of imagistic methods are available for diagnosing hepatosteatosis and choosing the one appropriate to the clinical context is the key. Although different in sensitivity and specificity when it comes to determining the hepatic fat fraction (FF), these imaging techniques possessing a diverse availability, operating difficulty, cost, and reproducibility are invaluable to any modern physician. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), elastography, and spectroscopy will be discussed in order to lay out the advantages and disadvantages of their diagnostic potential and application. Although imagistics has given physicians a valuable insight into the means of managing NAFLD, the current methods are far from perfect, but given the time, they will surely be improved and the use of liver biopsy will be completely removed. PMID:28255371

  13. Non-invasive imaging techniques in assessing non-alcoholic fatty liver disease: a current status of available methods.

    PubMed

    Lăpădat, A M; Jianu, I R; Ungureanu, B S; Florescu, L M; Gheonea, D I; Sovaila, S; Gheonea, I A

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an ailment affecting and increasing a number of people worldwide diagnosed via non-invasive imaging techniques, at a time when a minimum harm caused by medical procedures is rightfully emphasized, more sought after, than ever before. Liver steatosis should not be taken lightly even if its evolution is largely benign as it has the potential to develop into non-alcoholic steatohepatitis (NASH) or even more concerning, hepatic cirrhosis, and hepatocellular carcinoma (HCC). Traditionally, liver biopsy has been the standard for diagnosing this particular liver disease, but nowadays, a consistent number of imagistic methods are available for diagnosing hepatosteatosis and choosing the one appropriate to the clinical context is the key. Although different in sensitivity and specificity when it comes to determining the hepatic fat fraction (FF), these imaging techniques possessing a diverse availability, operating difficulty, cost, and reproducibility are invaluable to any modern physician. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), elastography, and spectroscopy will be discussed in order to lay out the advantages and disadvantages of their diagnostic potential and application. Although imagistics has given physicians a valuable insight into the means of managing NAFLD, the current methods are far from perfect, but given the time, they will surely be improved and the use of liver biopsy will be completely removed.

  14. The utilization of a non-invasive fluorescence imaging system to follow clinical dermatological MAL-PDT

    NASA Astrophysics Data System (ADS)

    Tyrrell, Jessica; Campbell, Sandra; Curnow, Alison

    2009-06-01

    This study employed a commercially available, non-invasive, fluorescence imaging system (Dyaderm, Biocam, Germany), to measure protoporphyrin IX (PpIX) concentration at several different stages during clinical dermatological methyl aminolevulinate photodynamic therapy (MAL-PDT). We validated the system prior to use to ensure that the PpIX changes witnessed were accurate and not due to environmental or user induced artifacts. The system was then employed to acquire color (morphological) and fluorescent (physiological) images simultaneously during dermatological PDT. Clinical data was collected from a range of licensed dermatological conditions (actinic keratosis, Bowen's disease and superficial basal cell carcinoma) during initial and subsequent PDT treatment cycles. The initial clinical data indicated that each type of licensed lesion considered responded in a similar manner following the application of Metvix (Galderma, U.K.) and the subsequent light irradiation (Aktilite, Galderma, U.K.). Images acquired three hours after Metvix application showed a significant increase in PpIX concentration within the lesion (P < 0.05), whilst PpIX levels in the surrounding normal tissue remained unaltered. After irradiation, the PpIX concentration was significantly decreased and returned to a level similar to the initial concentration originally observed. Lesions that received subsequent treatment cycles accumulated significantly less PpIX (P < 0.05) prior to irradiation.

  15. N-doped carbon nanodots for non-invasive photoacoustic imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Lee, Donghyun; Lee, Changho; Kwon, Woosung; Beack, Songeun; Kim, Chulhong

    2017-03-01

    We synthesized nitrogen-doped carbon nanodots (N-CNDs) for photoacoustic (PA) imaging and photothermal therapy (PTT) by controlling the nitrogen source and carbonizing organic acids. The N-CNDs showed strong optical absorbance in the near-infrared region, with great photostability and biodegradability. Thanks to the strong optical absorbance of NCNDs, the PA signals from N-CNDs were high enough to detect inside living animals and enabled minimally invasive PTT using N-CND. To evaluate the biodegradability and potential application of N-CNDs as a PA imaging contrast agent, we performed time-resolved PA imaging of sentinel lymph nodes (SLNs) and assessed renal clearance after hypodermic injection. SLN and vascular networks were photoacoustically visualized by an acoustic-resolution reflection-mode PA imaging system at a 680-nm optical wavelength. Furthermore, we performed whole-body PA imaging after subcutaneous injection of N-CNDs to assess their body distribution and clearance. Finally, we further investigated the use of N-CNDs for in vivo photothermal therapy in Balb/c nude xenograft HepG2-tumor model mice.

  16. Non-Invasive Magnetic Resonance Imaging of Nanoparticle Migration and Water Velocity Inside Sandstone

    NASA Astrophysics Data System (ADS)

    Phoenix, V. R.; Shukla, M.; Vallatos, A.; Riley, M. S.; Tellam, J. H.; Holmes, W. M.

    2015-12-01

    Manufactured nanoparticles (NPs) are already utilized in a diverse array of applications, including cosmetics, optics, medical technology, textiles and catalysts. Problematically, once in the natural environment, NPs can have a wide range of toxic effects. To protect groundwater from detrimental NPs we must be able to predict nanoparticle movement within the aquifer. The often complex transport behavior of nanoparticles ensures the development of NP transport models is not a simple task. To enhance our understanding of NP transport processes, we utilize novel magnetic resonance imaging (MRI) which enables us to look inside the rock and image the movement of nanoparticles within. For this, we use nanoparticles that are paramagnetic, making them visible to the MRI and enabling us to collect spatially resolved data from which we can develop more robust transport models. In this work, a core of Bentheimer sandstone (3 x 7 cm) was saturated with water and imaged inside a 7Tesla Bruker Biospec MRI. Firstly the porosity of the core was mapped using a MSME MRI sequence. Prior to imaging NP transport, the velocity of water (in absence on nanoparticles) was mapped using an APGSTE-RARE sequence. Nano-magnetite nanoparticles were then pumped into the core and their transport through the core was imaged using a RARE sequence. These images were calibrated using T2 parameter maps to provide fully quantitative maps of nanoparticle concentration at regular time intervals throughout the column (T2 being the spin-spin relaxation time of 1H nuclei). This work demonstrated we are able to spatially resolve porosity, water velocity and nanoparticle movement, inside rock, using a single technique (MRI). Significantly, this provides us with a unique and powerful dataset from which we are now developing new models of nanoparticle transport.

  17. Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins

    NASA Astrophysics Data System (ADS)

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-01

    The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm- 1 and 1545 cm- 1, respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties.

  18. Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins.

    PubMed

    Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

    2016-03-05

    The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm(-1) and 1545 cm(-1), respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties.

  19. Line-scanning Brillouin microscopy for rapid non-invasive mechanical imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Jitao; Fiore, Antonio; Yun, Seok-Hyun; Kim, Hanyoup; Scarcelli, Giuliano

    2016-10-01

    Brillouin spectroscopy probes the mechanical properties of material by measuring the optical frequency shift induced by photon-phonon scattering interactions. In traditional configurations, Brillouin spectrometers measure only one point of the sample at a time. This results in long acquisition times for mechanical imaging of large areas. In this work, we demonstrate a parallel detection configuration where the Brillouin shift of hundreds of points in a line can be measured simultaneously. In mm-sized samples, this novel configuration effectively shortens the acquisition time of two-dimensional Brillouin imaging from hours to tens of seconds, thus making it a powerful technology for label-free mechanical characterization of tissue and biomaterials.

  20. Line-scanning Brillouin microscopy for rapid non-invasive mechanical imaging.

    PubMed

    Zhang, Jitao; Fiore, Antonio; Yun, Seok-Hyun; Kim, Hanyoup; Scarcelli, Giuliano

    2016-10-14

    Brillouin spectroscopy probes the mechanical properties of material by measuring the optical frequency shift induced by photon-phonon scattering interactions. In traditional configurations, Brillouin spectrometers measure only one point of the sample at a time. This results in long acquisition times for mechanical imaging of large areas. In this work, we demonstrate a parallel detection configuration where the Brillouin shift of hundreds of points in a line can be measured simultaneously. In mm-sized samples, this novel configuration effectively shortens the acquisition time of two-dimensional Brillouin imaging from hours to tens of seconds, thus making it a powerful technology for label-free mechanical characterization of tissue and biomaterials.

  1. Rapid non-invasive mechanical imaging using line-scanning Brillouin microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhang, Jitao; Fiore, Antonio; Yun, Seok-Hyun; Kim, Hanyoup; Scarcelli, Giuliano

    2017-02-01

    Brillouin spectroscopy is able to measure material's mechanical properties by analyzing the optical spectrum of acoustically-induced light scattering within a sample. In the past decade, the development of high-resolution Brillouin spectrometers based on virtually-imaged phased array (VIPA) has greatly increased the spectral detection efficiency thus enabling mechanical characterization of biological tissue and biomaterials. Further improvements in spectrometer performances have enabled in vivo measurements at safe power levels and 2D/3D imaging of biological cells. However, it remains a slow technique compared to other imaging modalities, because only one point of the sample can be measured by the traditional backward-scattering configuration at a time. In this work, we demonstrate a parallel detection configuration with 90-degree geometry where the Brillouin shift of hundreds of points in a line can be measured simultaneously. In a 1.1mm-by-1.5mm samples, this novel configuration effectively shortens the acquisition time of 2D Brillouin imaging from hours to 30 seconds with spatial resolution of 3um, thus making it a powerful technology for label-free mechanical characterization of tissue and biomaterials.

  2. Line-scanning Brillouin microscopy for rapid non-invasive mechanical imaging

    PubMed Central

    Zhang, Jitao; Fiore, Antonio; Yun, Seok-Hyun; Kim, Hanyoup; Scarcelli, Giuliano

    2016-01-01

    Brillouin spectroscopy probes the mechanical properties of material by measuring the optical frequency shift induced by photon-phonon scattering interactions. In traditional configurations, Brillouin spectrometers measure only one point of the sample at a time. This results in long acquisition times for mechanical imaging of large areas. In this work, we demonstrate a parallel detection configuration where the Brillouin shift of hundreds of points in a line can be measured simultaneously. In mm-sized samples, this novel configuration effectively shortens the acquisition time of two-dimensional Brillouin imaging from hours to tens of seconds, thus making it a powerful technology for label-free mechanical characterization of tissue and biomaterials. PMID:27739499

  3. Non-Invasive Detection of Axiliary Nodes by Contrast Enhanced Magnetic Resonance Imaging.

    DTIC Science & Technology

    1996-08-01

    were injected with FreundOs adjuvant to induce an inflammatory response in popliteal lymph nodes and similarly imaged. Conventional spin echo (CSE... lymph nodes to grow, or when they did grow they were small, < 2 mm). Thus the second year of the project focused on the study proposed for the...ratios (CNR) relative to muscle were calculated for each sequence and histopathologic correlation was obtained for all lymph nodes . Findings

  4. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent.

    PubMed

    Zhao, M; Beauregard, D A; Loizou, L; Davletov, B; Brindle, K M

    2001-11-01

    The C2 domain of synaptotagmin I, which binds to anionic phospholipids in cell membranes, was shown to bind to the plasma membrane of apoptotic cells by both flow cytometry and confocal microscopy. Conjugation of the protein to superparamagnetic iron oxide nanoparticles allowed detection of this binding using magnetic resonance imaging. Detection of apoptotic cells, using this novel contrast agent, was demonstrated both in vitro, with isolated apoptotic tumor cells, and in vivo, in a tumor treated with chemotherapeutic drugs.

  5. A novel indocyanine green nanoparticle probe for non invasive fluorescence imaging in vivo

    NASA Astrophysics Data System (ADS)

    Navarro, Fabrice P.; Berger, Michel; Goutayer, Mathieu; Guillermet, Stéphanie; Josserand, Véronique; Rizo, Philippe; Vinet, Françoise; Texier, Isabelle

    2009-02-01

    Fluorescence imaging (FLI) allows the in vivo monitoring of biological events associated with disease and represents a new promising tool for drug discovery. In particular, it speeds up the development and assessment of new therapies in oncology, helps in diagnosis, and improves surgery by fluorescence-guided tumor resection. This technique is highly sensitive, non-ionizing, easy to use and relatively inexpensive. Nevertheless, the main limitation of FLI lies in the optical properties of biological tissues. Mainly because of haemoglobin and water absorption, only near-infrared (NIR) light is adapted to image tissues in depth. Using a contrasting agent absorbing and emitting in the NIR region is therefore necessary to improve the background signal ratio, and thus the image contrast. Among many commercially available NIR optical contrast agents, only indocyanine green (ICG), has been approved by the United State Food and Drug Administration (FDA) for various medical applications. However, its instability (photo-degradation, thermal-degradation and low aqueous solubility) limits its applications as a fluorescent probe for imaging purposes. In order to improve the effectiveness of ICG, we engineered ICG-doped lipid nanoparticles (LNP). In this communication, we will report the design of these novel fluorescent nanoparticle probes. These low cost nanocarriers have numerous advantages, including their high chemical stability and biocompatibility. The characterization of the optical properties of the nanoparticles entrapping ICG will also be discussed. Finally, the biodistribution in mice of ICG when delivered through nanoparticles in comparison to free ICG in solution is presented. It demonstrates the efficient accumulation of ICG-doped nanoparticles in the tumor site.

  6. Non-invasive prenatal testing using massively parallel sequencing of maternal plasma DNA: from molecular karyotyping to fetal whole-genome sequencing.

    PubMed

    Lo, Y M Dennis

    2013-12-01

    The discovery of cell-free fetal DNA in maternal plasma in 1997 has stimulated a rapid development of non-invasive prenatal testing. The recent advent of massively parallel sequencing has allowed the analysis of circulating cell-free fetal DNA to be performed with unprecedented sensitivity and precision. Fetal trisomies 21, 18 and 13 are now robustly detectable in maternal plasma and such analyses have been available clinically since 2011. Fetal genome-wide molecular karyotyping and whole-genome sequencing have now been demonstrated in a number of proof-of-concept studies. Genome-wide and targeted sequencing of maternal plasma has been shown to allow the non-invasive prenatal testing of β-thalassaemia and can potentially be generalized to other monogenic diseases. It is thus expected that plasma DNA-based non-invasive prenatal testing will play an increasingly important role in future obstetric care. It is thus timely and important that the ethical, social and legal issues of non-invasive prenatal testing be discussed actively by all parties involved in prenatal care. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  7. Biodegradable Nitrogen-Doped Carbon Nanodots for Non-Invasive Photoacoustic Imaging and Photothermal Therapy

    PubMed Central

    Lee, Changho; Kwon, Woosung; Beack, Songeun; Lee, Donghyun; Park, Yoonsang; Kim, Hyemin; Hahn, Sei Kwang; Rhee, Shi-Woo; Kim, Chulhong

    2016-01-01

    Multifunctional nanoparticles have been widely investigated for biomedical applications, such as imaging, therapy, and drug delivery. Especially, photoactive nanoparticles have received great attention as theranostic agents because of their heat-generating abilities after exposure to laser irradiation. However, photostability and safety issues have been the technical hurdles for further clinical applications. Here, we designed nitrogen (N)-doped carbon nanodots (N-CNDs) that have strong absorption in the near-infrared region, high photostability, and excellent biodegradability. Optimized N-CNDs can be utilized not only as a new photoacoustic (PA) imaging agent but also as a superior photothermal therapy (PTT) agent in vivo because of their strong optical absorption at a specific wavelength. We used N-CNDs to perform in vivo/ex vivo noninvasive PA imaging of sentinel lymph nodes via local delivery and performed PTT for cancer ablation therapy. Finally, biodegradation and renal clearance were confirmed by performing whole-body PA monitoring and a degradation test. PMID:27924157

  8. Non-invasive terahertz imaging of tissue water content for flap viability assessment

    PubMed Central

    Bajwa, Neha; Au, Joshua; Jarrahy, Reza; Sung, Shijun; Fishbein, Michael C.; Riopelle, David; Ennis, Daniel B.; Aghaloo, Tara; St. John, Maie A.; Grundfest, Warren S.; Taylor, Zachary D.

    2016-01-01

    Accurate and early prediction of tissue viability is the most significant determinant of tissue flap survival in reconstructive surgery. Perturbation in tissue water content (TWC) is a generic component of the tissue response to such surgeries, and, therefore, may be an important diagnostic target for assessing the extent of flap viability in vivo. We have previously shown that reflective terahertz (THz) imaging, a non-ionizing technique, can generate spatially resolved maps of TWC in superficial soft tissues, such as cornea and wounds, on the order of minutes. Herein, we report the first in vivo pilot study to investigate the utility of reflective THz TWC imaging for early assessment of skin flap viability. We obtained longitudinal visible and reflective THz imagery comparing 3 bipedicled flaps (i.e. survival model) and 3 fully excised flaps (i.e. failure model) in the dorsal skin of rats over a postoperative period of 7 days. While visual differences between both models manifested 48 hr after surgery, statistically significant (p < 0.05, independent t-test) local differences in TWC contrast were evident in THz flap image sets as early as 24 hr. Excised flaps, histologically confirmed as necrotic, demonstrated a significant, yet localized, reduction in TWC in the flap region compared to non-traumatized skin. In contrast, bipedicled flaps, histologically verified as viable, displayed mostly uniform, unperturbed TWC across the flap tissue. These results indicate the practical potential of THz TWC sensing to accurately predict flap failure 24 hours earlier than clinical examination. PMID:28101431

  9. In vivo non-invasive optical imaging of temperature-sensitive co-polymeric nanohydrogel

    NASA Astrophysics Data System (ADS)

    Chen, Haiyan; Zhang, Jian; Qian, Zhiyu; Liu, Fei; Chen, Xinyang; Hu, Yuzhu; Gu, Yueqing

    2008-05-01

    Assessment of hyperthermia in pathological tissue is a promising strategy for earlier diagnosis of malignant tumors. In this study, temperature-sensitive co-polymeric nanohydrogel poly(N-isopropylacrylamide-co-acrylic acid) (PNIPA-co-AA) was successfully synthesized by the precipitation polymerization method. The diameters of nanohydrogels were controlled to be less than 100 nm. Also the lower critical solution temperature (LCST, 40 °C) was manipulated above physiological temperature after integration of near-infrared (NIR) organic dye (heptamethine cyanine dye, HMCD) within its interior cores. NIR laser light (765 nm), together with sensitive charge coupled device (CCD) cameras, were designed to construct an NIR imaging system. The dynamic behaviors of PNIPA-co-AA-HMCD composites in denuded mice with or without local hyperthermia treatment were real-time monitored by an NIR imager. The results showed that the PNIPA-co-AA-HMCD composites accumulated in the leg treated with local heating and diffused much slower than that in the other leg without heating. The results demonstrated that the temperature-responsive PNIPA-co-AA-HMCD composites combining with an NIR imaging system could be an effective temperature mapping technique, which provides a promising prospect for earlier tumor diagnosis and thermally related therapeutic assessment.

  10. A Non-Invasive Imaging Approach to Understanding Speech Changes following Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Narayana, Shalini; Jacks, Adam; Robin, Donald A.; Poizner, Howard; Zhang, Wei; Franklin, Crystal; Liotti, Mario; Vogel, Deanie; Fox, Peter T.

    2009-01-01

    Purpose To explore the use of non-invasive functional imaging and “virtual” lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson’s disease. Here, we report the use of Positron Emission Tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson’s disease. Method Perceptual and acoustic speech measures as well as cerebral blood flow (CBF) during speech as measured by PET were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with that resulting from DBS on. Results Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during DBS on. “Virtual” lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. Conclusions This case report provides evidence that impaired speech production accompanying STN-DBS may be resulting from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities. PMID:19029533

  11. Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

    NASA Astrophysics Data System (ADS)

    Donnelley, Martin; Morgan, Kaye S.; Siu, Karen K. W.; Farrow, Nigel R.; Stahr, Charlene S.; Boucher, Richard C.; Fouras, Andreas; Parsons, David W.

    2014-01-01

    To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials.

  12. Fast spectroscopic imaging for non-invasive thermometry using the Pr[MOE-DO3A] complex.

    PubMed

    Hentschel, M; Dreher, W; Wust, P; Röll, S; Leibfritz, D; Felix, R

    1999-10-01

    The praseodymium complex of 10-(2-methoxyethyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7-tr iacetate) was evaluated as a temperature-sensitive contrast agent using the temperature dependence (approximately 0.12 ppm degrees C(-1)) of the chemical shift of its methoxy side group signal. Pr[MOE-DO3A] was employed in combination with spectroscopic imaging (SI) methods for the determination of spatially resolved 2D and 3D temperature distributions in phantoms. Conventional SI and fast echo planar SI sequences (EPSI) were implemented on a 4.7 T MR imaging system fulfilling the demands for non-invasive thermometry (NIT) with respect to thermal and temporal resolution, being <1 degree C and <20 s total measuring time, respectively. The sequences are based on a fast spin echo SI method taking into account the very short relaxation times of the Pr complex methoxy group (T1 = 28 ms, T2 = 13 ms) and its chemical shift difference (-24 ppm) from water. Calibration curves were measured in a uniformly heated water phantom and 2D SI methods were applied to dynamic heating experiments. The average differences between the temperatures measured via fibreoptic thermometer and those derived from the spectroscopic methods were < or =0.2 degrees C. Furthermore, 3D EPSI experiments with a 16 x 16 x 16 matrix size yielded temperature measurements within 17 s from voxels of size 3 x 3 x 3 mm3.

  13. Non-invasive in vivo imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin

    PubMed Central

    Kramer, Lovro; Renko, Miha; Završnik, Janja; Turk, Dušan; Seeger, Markus A.; Vasiljeva, Olga; Grütter, Markus G.; Turk, Vito; Turk, Boris

    2017-01-01

    Cysteine cathepsins often contribute to cancer progression due to their overexpression in the tumour microenvironment and therefore present attractive targets for non-invasive diagnostic imaging. However, the development of highly selective and versatile small molecule probes for cathepsins has been challenging. Here, we targeted tumour-associated cathepsin B using designed ankyrin repeat proteins (DARPins). The selective DARPin 8h6 inhibited cathepsin B with picomolar affinity (Ki = 35 pM) by binding to a site with low structural conservation in cathepsins, as revealed by the X-ray structure of the complex. DARPin 8h6 blocked cathepsin B activity in tumours ex vivo and was successfully applied in in vivo optical imaging in two mouse breast cancer models, in which cathepsin B was bound to the cell membrane or secreted to the extracellular milieu by tumour and stromal cells. Our approach validates cathepsin B as a promising diagnostic and theranostic target in cancer and other inflammation-associated diseases. PMID:28824717

  14. New imaging technique using degree of polarization for the study of polarimetric properties for non-invasive biomedical diagnostic

    NASA Astrophysics Data System (ADS)

    Buscemi, Isabella C.; Guyot, Steve; Lemoine, Jacques

    2012-06-01

    This research proposes a new imaging technique for near real time multispectral acquisition using CCD RGB cameras of the so called "Degree Of Polarization" (DOP) in polarimetry for future clinical investigation. The aim of exploiting the DOP as the contrast element is to demonstrate that the elliptical DOP provides more information characterizing complex medium than the more traditional linear and circular ones. The system considers an incoherent input white light beam and opportunely calibrated nematic crystals (LCVR), so no mechanical tools are necessary. The particular features of the system indicate it to be the perfect candidate for a new imaging system considering in-vivo (as well as ex-vivo) non invasive superficial diagnostic for medical application as dermatologic diagnostics, since no type of sample preparation is necessary, i.e. tissue biopsy, radiation or contrast agent injection. Thus the biomedical application of this method suggests a simple, direct, fast and also easily exploitable future employment, as a desirable mean for clinical investigation but also for digital recognition in biometrics. Further new elements to improve the model of light scattering and matter-light interaction will be acquired, in particular considering a very complete characterization of the system response using latex microspheres suspension to simulate turbid media with different concentration.

  15. Cardiovascular complications of radiation therapy for thoracic malignancies: the role for non-invasive imaging for detection of cardiovascular disease

    PubMed Central

    Groarke, John D.; Nguyen, Paul L.; Nohria, Anju; Ferrari, Roberto; Cheng, Susan; Moslehi, Javid

    2014-01-01

    Radiation exposure to the thorax is associated with substantial risk for the subsequent development of cardiovascular disease. Thus, the increasing role of radiation therapy in the contemporary treatment of cancer, combined with improving survival rates of patients undergoing this therapy, contributes to a growing population at risk of cardiovascular morbidity and mortality. Associated cardiovascular injuries include pericardial disease, coronary artery disease, valvular disease, conduction disease, cardiomyopathy, and medium and large vessel vasculopathy—any of which can occur at varying intervals following irradiation. Higher radiation doses, younger age at the time of irradiation, longer intervals from the time of radiation, and coexisting cardiovascular risk factors all predispose to these injuries. The true incidence of radiation-related cardiovascular disease remains uncertain due to lack of large multicentre studies with a sufficient duration of cardiovascular follow-up. There are currently no consensus guidelines available to inform the optimal approach to cardiovascular surveillance of recipients of thoracic radiation. Therefore, we review the cardiovascular consequences of radiation therapy and focus on the potential role of non-invasive cardiovascular imaging in the assessment and management of radiation-related cardiovascular disease. In doing so, we highlight characteristics that can be used to identify individuals at risk for developing post-radiation cardiovascular disease and propose an imaging-based algorithm for their clinical surveillance. PMID:23666251

  16. Exploiting multispectral imaging for non-invasive contamination assessment and mapping of meat samples.

    PubMed

    Tsakanikas, Panagiotis; Pavlidis, Dimitris; Panagou, Efstathios; Nychas, George-John

    2016-12-01

    Recently, imaging and machine vision are gaining attention to food stakeholders since these are considered to be the emerging tools for food safety and quality assessment throughout the whole food chain. Herein, multispectral imaging, a surface chemistry sensor type, has been evaluated in terms of monitoring aerobically packaged beef filet spoilage at different storage temperatures (2, 8, and 15°C) and storage time. Spectral data acquired from the surface of meat samples (with/without background flora; +BF/-BF respectively) along with microbiological analysis. Qualitative analysis was employed for the discrimination of meat samples in two microbiological quality classes based on the values of total viable counts (TVC<2log10CFU/g and TVC>2log10CFU/g). Furthermore, a Support Vector Regression model was developed to provide quantitative estimations of microbial counts during storage. Results exhibit good performance with overall correct classification rate for the two quality classes ranging from 89.2% to 80.8% for model validation. The calculated regression results to an R-square of 0.98. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Non-invasive ultrasound-based temperature imaging for monitoring radiofrequency heating—phantom results

    NASA Astrophysics Data System (ADS)

    Daniels, M. J.; Varghese, T.; Madsen, E. L.; Zagzebski, J. A.

    2007-08-01

    Minimally invasive therapies (such as radiofrequency ablation) are becoming more commonly used in the United States for the treatment of hepatocellular carcinomas and liver metastases. Unfortunately, these procedures suffer from high recurrence rates of hepatocellular carcinoma (~34-55%) or metastases following ablation therapy. The ability to perform real-time temperature imaging while a patient is undergoing radiofrequency ablation could provide a significant reduction in these recurrence rates. In this paper, we demonstrate the feasibility of ultrasound-based temperature imaging on a tissue-mimicking phantom undergoing radiofrequency heating. Ultrasound echo signals undergo time shifts with increasing temperature, which are tracked using 2D correlation-based speckle tracking methods. Time shifts or displacements in the echo signal are accumulated, and the gradient of these time shifts are related to changes in the temperature of the tissue-mimicking phantom material using a calibration curve generated from experimental data. A tissue-mimicking phantom was developed that can undergo repeated radiofrequency heating procedures. Both sound speed and thermal expansion changes of the tissue-mimicking material were measured experimentally and utilized to generate the calibration curve relating temperature to the displacement gradient. Temperature maps were obtained, and specific regions-of-interest on the temperature maps were compared to invasive temperatures obtained using fiber-optic temperature probes at the same location. Temperature elevation during a radiofrequency ablation procedure on the phantom was successfully tracked to within ±0.5 °C.

  18. [Large left ventricular aneurysm after silent myocardial infarction. Documentation by serial non-invasive imaging].

    PubMed

    Ritter, C; Beer, M; Weidemann, F; Strotmann, J; Müllges, W; Mohr, F W; Ertl, G; Hahn, D; Bauersachs, J

    2008-03-01

    A 60-year-old man had a workup for atypical angina. Noninvasive investigations, including computed tomography, showed no evidence for coronary artery disease. A few months later the patient was hospitalized because of severe epileptic seizures. Thyrotoxicosis was diagnosed and emergency thyroidectomy was performed. Two months after discharge the patient was again referred because of exercise-induced angina pectoris. Echocardiography and cardiac magnetic resonance imaging (MRI) showed a large aneurysm of the lateral wall of the left ventricle with a thrombus adhering to the wall. Coronary angiography and levocardiography confirmed the aneurysm and detected an occlusion of the distal part of the circumflex artery. Surgical aneurysm resection with thrombectomy and endoventricular circular plasty (Dor procedure) was performed without postoperative complications. Six months after surgery the patient was in good general condition without any angina. Follow-up echocardiography as well as cardiac MRI gave proof of an excellent postoperative result. Noninvasive preoperative diagnosis and documentation as well as postoperative monitoring with modern imaging modalities, such as echocardiography and MRI are of great value in patients with left ventricular aneurysm.

  19. Non-invasive optical imaging of tumor growth in intact animals

    NASA Astrophysics Data System (ADS)

    Lu, Jinling; Li, Pengcheng; Luo, Qingming; Zhu, Dan

    2003-12-01

    We describe here a system for rapidly visualizing tumor growth in intact rodent mice that is simple, rapid, and eminently accessible and repeatable. We have established new rodent tumor cell line -- SP2/0-GFP cells that stably express high level of green fluorescent protein (GFP) by transfected with a plasmid that encoded GFP using electroporation and selected with G418 for 3 weeks. 1 x 104 - 1x107 SP2/0-GFP mouse melanoma cells were injected s.c. in the ears and legs of 6- to 7-week-old syngeneic male BALB/c mice, and optical images visualized real-time the engrafted tumor growth. The tumor burden was monitored over time by cryogenically cooled charge coupled device (CCD) camera focused through a stereo microscope. The results show that the fluorescence intensity of GFP-expressing tumor is comparably with the tumor growth and/or depress. This in vivo optical imaging based on GFP is sensitive, external, and noninvasive. It affords continuous visual monitoring of malignant growth within intact animals, and may comprise an ideal tool for evaluating antineoplastic therapies.

  20. Non-invasive ultrasound-based temperature imaging for monitoring radiofrequency heating-phantom results.

    PubMed

    Daniels, M J; Varghese, T; Madsen, E L; Zagzebski, J A

    2007-08-21

    Minimally invasive therapies (such as radiofrequency ablation) are becoming more commonly used in the United States for the treatment of hepatocellular carcinomas and liver metastases. Unfortunately, these procedures suffer from high recurrence rates of hepatocellular carcinoma ( approximately 34-55%) or metastases following ablation therapy. The ability to perform real-time temperature imaging while a patient is undergoing radiofrequency ablation could provide a significant reduction in these recurrence rates. In this paper, we demonstrate the feasibility of ultrasound-based temperature imaging on a tissue-mimicking phantom undergoing radiofrequency heating. Ultrasound echo signals undergo time shifts with increasing temperature, which are tracked using 2D correlation-based speckle tracking methods. Time shifts or displacements in the echo signal are accumulated, and the gradient of these time shifts are related to changes in the temperature of the tissue-mimicking phantom material using a calibration curve generated from experimental data. A tissue-mimicking phantom was developed that can undergo repeated radiofrequency heating procedures. Both sound speed and thermal expansion changes of the tissue-mimicking material were measured experimentally and utilized to generate the calibration curve relating temperature to the displacement gradient. Temperature maps were obtained, and specific regions-of-interest on the temperature maps were compared to invasive temperatures obtained using fiber-optic temperature probes at the same location. Temperature elevation during a radiofrequency ablation procedure on the phantom was successfully tracked to within +/-0.5 degrees C.

  1. A FRET sensor for non-invasive imaging of amyloid formation in vivo.

    PubMed

    Kaminski Schierle, Gabriele S; Bertoncini, Carlos W; Chan, Fiona T S; van der Goot, Annemieke T; Schwedler, Stefanie; Skepper, Jeremy; Schlachter, Simon; van Ham, Tjakko; Esposito, Alessandro; Kumita, Janet R; Nollen, Ellen A A; Dobson, Christopher M; Kaminski, Clemens F

    2011-02-25

    Misfolding and aggregation of amyloidogenic polypeptides lie at the root of many neurodegenerative diseases. Whilst protein aggregation can be readily studied in vitro by established biophysical techniques, direct observation of the nature and kinetics of aggregation processes taking place in vivo is much more challenging. We describe here, however, a Förster resonance energy transfer sensor that permits the aggregation kinetics of amyloidogenic proteins to be quantified in living systems by exploiting our observation that amyloid assemblies can act as energy acceptors for variants of fluorescent proteins. The observed lifetime reduction can be attributed to fluorescence energy transfer to intrinsic energy states associated with the growing amyloid species. Indeed, for a-synuclein, a protein whose aggregation is linked to Parkinson's disease, we have used this sensor to follow the kinetics of the self-association reactions taking place in vitro and in vivo and to reveal the nature of the ensuing aggregated species. Experiments were conducted in vitro, in cells in culture and in living Caenorhabditis elegans. For the latter the readout correlates directly with the appearance of a toxic phenotype. The ability to measure the appearance and development of pathogenic amyloid species in a living animal and the ability to relate such data to similar processes observed in vitro provides a powerful new tool in the study of the pathology of the family of misfolding disorders. Our study confirms the importance of the molecular environment in which aggregation reactions take place, highlighting similarities as well as differences between the processes occurring in vitro and in vivo, and their significance for defining the molecular physiology of the diseases with which they are associated. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Non-invasive analysis of root-soil interaction using three complementary imaging approaches

    NASA Astrophysics Data System (ADS)

    Haber-Pohlmeier, Sabina; Tötzke, Christian; Pohlmeier, Andreas; Rudolph-Mohr, Nicole; Kardjilov, Nikolay; Lehmann, Eberhard; Oswald, Sascha E.

    2016-04-01

    Plant roots are known to modify physical, chemical and biological properties of the rhizosphere, thereby, altering conditions for water and nutrient uptake. We aim for capturing the dynamic processes occurring at the soil-root interface in situ. A combination of neutron (NI), magnetic resonance (MRI) and micro-focus X-ray tomography (CT) is applied to monitor the rhizosphere of young plants grown in sandy soil in cylindrical containers (diameter 3 cm). A novel transportable low field MRI system is operated directly at the neutron facility allowing for combined measurements of the very same sample capturing the same hydro-physiological state. The combination of NI, MRI and CT provides three-dimensional access to the root system in respect to structure and hydraulics of the rhizosphere and the transport of dissolved marker substances. The high spatial resolution of neutron imaging and its sensitivity for water can be exploited for the 3D analysis of the root morphology and detailed mapping of three-dimensional water content at the root soil interface and the surrounding soil. MRI has the potential to yield complementary information about the mobility of water, which can be bound in small pores or in the polymeric network of root exudates (mucilage layer). We inject combined tracers (GdDPTA or D2O) to study water fluxes through soil, rhizosphere and roots. Additional CT measurements reveal mechanical impacts of roots on the local microstructure of soil, e.g. showing soil compaction or the formation of cracks. We co-register the NT, MRI and CT data to integrate the complementary information into an aligned 3D data set. This allows, e.g., for co-localization of compacted soil regions or cracks with the specific local soil hydraulics, which is needed to distinguish the contribution of root exudation from mechanical impacts when interpreting altered hydraulic properties of the rhizosphere. Differences between rhizosphere and bulk soil can be detected and interpreted in

  3. Thermal fluctuation based study of aqueous deficient dry eyes by non-invasive thermal imaging.

    PubMed

    Azharuddin, Mohammad; Bera, Sumanta Kr; Datta, Himadri; Dasgupta, Anjan Kr

    2014-03-01

    In this paper we have studied the thermal fluctuation patterns occurring at the ocular surface of the left and right eyes for aqueous deficient dry eye (ADDE) patients and control subjects by thermal imaging. We conducted our experiment on 42 patients (84 eyes) with aqueous deficient dry eyes and compared with 36 healthy volunteers (72 eyes) without any history of ocular surface disorder. Schirmer's test, Tear Break-up Time, tear Meniscus height and fluorescein staining tests were conducted. Ocular surface temperature measurement was done, using an FL-IR thermal camera and thermal fluctuation in left and right eyes was calculated and analyzed using MATLAB. The time series containing the sum of squares of the temperature fluctuation on the ocular surface were compared for aqueous deficient dry eye and control subjects. Significant statistical difference between the fluctuation patterns for control and ADDE was observed (p < 0.001 at 95% confidence interval). Thermal fluctuations in left and right eyes are significantly correlated in controls but not in ADDE subjects. The possible origin of such correlation in control and lack of correlation in the ADDE subjects is discussed in the text.

  4. Non invasive blood flow assessment in diabetic foot ulcer using laser speckle contrast imaging technique

    NASA Astrophysics Data System (ADS)

    Jayanthy, A. K.; Sujatha, N.; Reddy, M. Ramasubba; Narayanamoorthy, V. B.

    2014-03-01

    Measuring microcirculatory tissue blood perfusion is of interest for both clinicians and researchers in a wide range of applications and can provide essential information of the progress of treatment of certain diseases which causes either an increased or decreased blood flow. Diabetic ulcer associated with alterations in tissue blood flow is the most common cause of non-traumatic lower extremity amputations. A technique which can detect the onset of ulcer and provide essential information on the progress of the treatment of ulcer would be of great help to the clinicians. A noninvasive, noncontact and whole field laser speckle contrast imaging (LSCI) technique has been described in this paper which is used to assess the changes in blood flow in diabetic ulcer affected areas of the foot. The blood flow assessment at the wound site can provide critical information on the efficiency and progress of the treatment given to the diabetic ulcer subjects. The technique may also potentially fulfill a significant need in diabetic foot ulcer screening and management.

  5. Non-invasive imaging of the crystalline structure within a human tooth.

    PubMed

    Egan, Christopher K; Jacques, Simon D M; Di Michiel, Marco; Cai, Biao; Zandbergen, Mathijs W; Lee, Peter D; Beale, Andrew M; Cernik, Robert J

    2013-09-01

    The internal crystalline structure of a human molar tooth has been non-destructively imaged in cross-section using X-ray diffraction computed tomography. Diffraction signals from high-energy X-rays which have large attenuation lengths for hard biomaterials have been collected in a transmission geometry. Coupling this with a computed tomography data acquisition and mathematically reconstructing their spatial origins, diffraction patterns from every voxel within the tooth can be obtained. Using this method we have observed the spatial variations of some key material parameters including nanocrystallite size, organic content, lattice parameters, crystallographic preferred orientation and degree of orientation. We have also made a link between the spatial variations of the unit cell lattice parameters and the chemical make-up of the tooth. In addition, we have determined how the onset of tooth decay occurs through clear amorphization of the hydroxyapatite crystal, and we have been able to map the extent of decay within the tooth. The described method has strong prospects for non-destructive probing of mineralized biomaterials.

  6. Non-invasive deep tissue imaging of iodine modified poly(caprolactone-co-1-4-oxepan-1,5-dione) using X-ray.

    PubMed

    Olsen, Timothy R; Davis, Lundy L; Nicolau, Samantha E; Duncan, Caroline C; Whitehead, Daniel C; Van Horn, Brooke A; Alexis, Frank

    2015-07-01

    When biodegradable polyester devices, like sutures and screws, are implanted into the body, it is very challenging to image them in deep tissue, monitor their degradation, and detect defects. We report our recent findings on non-invasive deep tissue imaging of polyester degradation, stability and integrity using an iodinated-polycaprolactone (i-P(CLcoOPD)) X-ray imaging contrast agent. The results of experiments performed with i-P(CLcoOPD) demonstrate the feasibility to quantify in-situ polyester degradation in vitro and in vivo using rats. We also demonstrate that X-ray imaging could be used to identify and quantify physical defects, such as cracks, in polymeric implants using rabbit animal models. This approach enables non-invasive monitoring of polyester materials and is expected to become an important technology for improving the imaging of polymers at clinically relevant depths.

  7. Non-invasive monitoring of ultrasound-stimulated microbubble radiation enhancement using photoacoustic imaging.

    PubMed

    Briggs, K; Al Mahrouki, A; Nofiele, J; El-Falou, A; Stanisz, M; Kim, H C; Kolios, M C; Czarnota, G J

    2014-10-01

    Modulation of the tumour microvasculature has been demonstrated to affect the effectiveness of radiation, stimulating the search for anti-angiogenic and vascular-disrupting treatment modalities. Microbubbles stimulated by ultrasound have recently been demonstrated as a radiation enhancer when used with different cancer models including PC3. Here, photoacoustics imaging technique was used to assess this treatment's effects on haemoglobin levels and oxygen saturation. Correlations between this modality and power doppler assessments of blood flow, and histology measurements of vascular integrity and cell death were also investigated. Xenograft prostate tumours in SCID mice were treated with 0, 2, or 8 Gy radiation combined with microbubbles exposed to 500 kHz ultrasound at a peak negative pressure of 0, 570, and 750 kPa. Tumours were assessed and levels of total haemoglobin, oxygen saturation were measured using photoacoustics before and 24 hours after treatment along with power doppler measured blood flow. Mice were then sacrificed and tumours were assessed for cell death and vascular composition using immunohistochemistry. Treatments using 8 Gy and microbubbles resulted in oxygen saturation decreasing by 28 ± 10% at 570 kPa and 25 ± 29% at 750 kPa, which corresponded to 44 ± 9% and 40 ± 14% respective decreases in blood flow as measured with power doppler. Corresponding histology indicated 31 ± 5% at 570 kPa and 37 ± 5% at 750 kPa in terms of cell death. There were drops in intact vasculature of 15 ± 2% and 20 ± 2%, for treatments at 570 kPa and 750 kPa. In summary, photoacoustic measures of total haemoglobin and oxygen saturation paralleled changes in power doppler indicators of blood flow. Destruction of tumour microvasculature with microbubble-enhanced radiation also led to decreases in blood flow and was associated with increases in cell death and decreases in intact vasculature as detected with CD31 labeling.

  8. High-Resolution, Non-Invasive Imaging of Upper Vocal Tract Articulators Compatible with Human Brain Recordings

    DOE PAGES

    Bouchard, Kristofer E.; Conant, David F.; Anumanchipalli, Gopala K.; ...

    2016-03-28

    A complete neurobiological understanding of speech motor control requires determination of the relationship between simultaneously recorded neural activity and the kinematics of the lips, jaw, tongue, and larynx. Many speech articulators are internal to the vocal tract, and therefore simultaneously tracking the kinematics of all articulators is nontrivial-especially in the context of human electrophysiology recordings. Here, we describe a noninvasive, multi-modal imaging system to monitor vocal tract kinematics, demonstrate this system in six speakers during production of nine American English vowels, and provide new analysis of such data. Classification and regression analysis revealed considerable variability in the articulator-to-acoustic relationship acrossmore » speakers. Non-negative matrix factorization extracted basis sets capturing vocal tract shapes allowing for higher vowel classification accuracy than traditional methods. Statistical speech synthesis generated speech from vocal tract measurements, and we demonstrate perceptual identification. We demonstrate the capacity to predict lip kinematics from ventral sensorimotor cortical activity. These results demonstrate a multi-modal system to non-invasively monitor articulator kinematics during speech production, describe novel analytic methods for relating kinematic data to speech acoustics, and provide the first decoding of speech kinematics from electrocorticography. These advances will be critical for understanding the cortical basis of speech production and the creation of vocal prosthetics.« less

  9. High-resolution non-invasive 3D imaging of paint microstructure by synchrotron-based X-ray laminography

    NASA Astrophysics Data System (ADS)

    Reischig, Péter; Helfen, Lukas; Wallert, Arie; Baumbach, Tilo; Dik, Joris

    2013-06-01

    The characterisation of the microstructure and micromechanical behaviour of paint is key to a range of problems related to the conservation or technical art history of paintings. Synchrotron-based X-ray laminography is demonstrated in this paper to image the local sub-surface microstructure in paintings in a non-invasive and non-destructive way. Based on absorption and phase contrast, the method can provide high-resolution 3D maps of the paint stratigraphy, including the substrate, and visualise small features, such as pigment particles, voids, cracks, wood cells, canvas fibres etc. Reconstructions may be indicative of local density or chemical composition due to increased attenuation of X-rays by elements of higher atomic number. The paint layers and their interfaces can be distinguished via variations in morphology or composition. Results of feasibility tests on a painting mockup (oak panel, chalk ground, vermilion and lead white paint) are shown, where lateral and depth resolution of up to a few micrometres is demonstrated. The method is well adapted to study the temporal evolution of the stratigraphy in test specimens and offers an alternative to destructive sampling of original works of art.

  10. High-Resolution, Non-Invasive Imaging of Upper Vocal Tract Articulators Compatible with Human Brain Recordings

    SciTech Connect

    Bouchard, Kristofer E.; Conant, David F.; Anumanchipalli, Gopala K.; Dichter, Benjamin; Chaisanguanthum, Kris S.; Johnson, Keith; Chang, Edward F.; Gribble, Paul L.

    2016-03-28

    A complete neurobiological understanding of speech motor control requires determination of the relationship between simultaneously recorded neural activity and the kinematics of the lips, jaw, tongue, and larynx. Many speech articulators are internal to the vocal tract, and therefore simultaneously tracking the kinematics of all articulators is nontrivial-especially in the context of human electrophysiology recordings. Here, we describe a noninvasive, multi-modal imaging system to monitor vocal tract kinematics, demonstrate this system in six speakers during production of nine American English vowels, and provide new analysis of such data. Classification and regression analysis revealed considerable variability in the articulator-to-acoustic relationship across speakers. Non-negative matrix factorization extracted basis sets capturing vocal tract shapes allowing for higher vowel classification accuracy than traditional methods. Statistical speech synthesis generated speech from vocal tract measurements, and we demonstrate perceptual identification. We demonstrate the capacity to predict lip kinematics from ventral sensorimotor cortical activity. These results demonstrate a multi-modal system to non-invasively monitor articulator kinematics during speech production, describe novel analytic methods for relating kinematic data to speech acoustics, and provide the first decoding of speech kinematics from electrocorticography. These advances will be critical for understanding the cortical basis of speech production and the creation of vocal prosthetics.

  11. High-Resolution, Non-Invasive Imaging of Upper Vocal Tract Articulators Compatible with Human Brain Recordings

    PubMed Central

    Anumanchipalli, Gopala K.; Dichter, Benjamin; Chaisanguanthum, Kris S.; Johnson, Keith; Chang, Edward F.

    2016-01-01

    A complete neurobiological understanding of speech motor control requires determination of the relationship between simultaneously recorded neural activity and the kinematics of the lips, jaw, tongue, and larynx. Many speech articulators are internal to the vocal tract, and therefore simultaneously tracking the kinematics of all articulators is nontrivial—especially in the context of human electrophysiology recordings. Here, we describe a noninvasive, multi-modal imaging system to monitor vocal tract kinematics, demonstrate this system in six speakers during production of nine American English vowels, and provide new analysis of such data. Classification and regression analysis revealed considerable variability in the articulator-to-acoustic relationship across speakers. Non-negative matrix factorization extracted basis sets capturing vocal tract shapes allowing for higher vowel classification accuracy than traditional methods. Statistical speech synthesis generated speech from vocal tract measurements, and we demonstrate perceptual identification. We demonstrate the capacity to predict lip kinematics from ventral sensorimotor cortical activity. These results demonstrate a multi-modal system to non-invasively monitor articulator kinematics during speech production, describe novel analytic methods for relating kinematic data to speech acoustics, and provide the first decoding of speech kinematics from electrocorticography. These advances will be critical for understanding the cortical basis of speech production and the creation of vocal prosthetics. PMID:27019106

  12. On non-invasive 2D and 3D Chromatic White Light image sensors for age determination of latent fingerprints.

    PubMed

    Merkel, Ronny; Gruhn, Stefan; Dittmann, Jana; Vielhauer, Claus; Bräutigam, Anja

    2012-10-10

    The feasibility of 2D-intensity and 3D-topography images from a non-invasive Chromatic White Light (CWL) sensor for the age determination of latent fingerprints is investigated. The proposed method might provide the means to solve the so far unresolved issue of determining a fingerprints age in forensics. Conducting numerous experiments for an indoor crime scene using selected surfaces, different influences on the aging of fingerprints are investigated and the resulting aging variability is determined in terms of inter-person, intra-person, inter-finger and intra-finger variation. Main influence factors are shown to be the sweat composition, temperature, humidity, wind, UV-radiation, surface type, contamination of the finger with water-containing substances, resolution and measured area size, whereas contact time, contact pressure and smearing of the print seem to be of minor importance. Such influences lead to a certain experimental variability in inter-person and intra-person variation, which is higher than the inter-finger and intra-finger variation. Comparing the aging behavior of 17 different features using 1490 time series with a total of 41,520 fingerprint images, the great potential of the CWL technique in combination with the binary pixel feature from prior work is shown. Performing three different experiments for the classification of fingerprints into the two time classes [0, 5 h] and [5, 24 h], a maximum classification performance of 79.29% (kappa=0.46) is achieved for a general case, which is further improved for special cases. The statistical significance of the two best-performing features (both binary pixel versions based on 2D-intensity images) is manually shown and a feature fusion is performed, highlighting the strong dependency of the features on each other. It is concluded that such method might be combined with additional capturing devices, such as microscopes or spectroscopes, to a very promising age estimation scheme.

  13. Continuing Education Course #1: Non-Invasive Imaging as a Problem-Solving Tool and Translational Biomarker Strategy in Toxicologic Pathology

    PubMed Central

    Peterson, Richard A.; Gabrielson, Kathy L.; Johnson, G. Allan; Pomper, Martin G.; Coatney, Robert W.; Winkelmann, Christopher T.

    2012-01-01

    The continuing education course “Non-Invasive Imaging as a Problem-Solving Tool and Translational Biomarker Strategy in Toxicologic Pathology” provided a thorough overview of commonly used imaging modalities and the logistics required for integration of small animal imaging into toxicologic pathology. Non-invasive imaging (NIN) is gaining acceptance as an important modality in toxicologic pathology. This technology allows non-terminal, time-course evaluation of functional and morphologic endpoints and can be used to translate biomarkers between preclinical animal models and human patients. Non-invasive imaging can support drug development as well as basic research in academic or industrial environments. An initial overview of theoretical principles was followed by focused presentations on magnetic resonance imaging (MRI)/magnetic resonance microscopy (MRM), positron emission tomography (PET)/single proton emission computed tomography (SPECT), ultrasonography (US, primarily focused on echocardiography), optical (bioluminescent) imaging, and computed tomography (CT). The choice of imaging modality will depend on the research question and the needed resolution. PMID:21147931

  14. Utility of spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) to non-invasively diagnose burn depth in a porcine model☆

    PubMed Central

    Burmeister, David M.; Ponticorvo, Adrien; Yang, Bruce; Becerra, Sandra C.; Choi, Bernard; Durkin, Anthony J.; Christy, Robert J.

    2015-01-01

    Surgical intervention of second degree burns is often delayed because of the difficulty in visual diagnosis, which increases the risk of scarring and infection. Non-invasive metrics have shown promise in accurately assessing burn depth. Here, we examine the use of spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) for predicting burn depth. Contact burn wounds of increasing severity were created on the dorsum of a Yorkshire pig, and wounds were imaged with SFDI/LSI starting immediately after-burn and then daily for the next 4 days. In addition, on each day the burn wounds were biopsied for histological analysis of burn depth, defined by collagen coagulation, apoptosis, and adnexal/vascular necrosis. Histological results show that collagen coagulation progressed from day 0 to day 1, and then stabilized. Results of burn wound imaging using non-invasive techniques were able to produce metrics that correlate to different predictors of burn depth. Collagen coagulation and apoptosis correlated with SFDI scattering coefficient parameter ( μs′) and adnexal/vascular necrosis on the day of burn correlated with blood flow determined by LSI. Therefore, incorporation of SFDI scattering coefficient and blood flow determined by LSI may provide an algorithm for accurate assessment of the severity of burn wounds in real time. PMID:26138371

  15. Utility of spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) to non-invasively diagnose burn depth in a porcine model.

    PubMed

    Burmeister, David M; Ponticorvo, Adrien; Yang, Bruce; Becerra, Sandra C; Choi, Bernard; Durkin, Anthony J; Christy, Robert J

    2015-09-01

    Surgical intervention of second degree burns is often delayed because of the difficulty in visual diagnosis, which increases the risk of scarring and infection. Non-invasive metrics have shown promise in accurately assessing burn depth. Here, we examine the use of spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) for predicting burn depth. Contact burn wounds of increasing severity were created on the dorsum of a Yorkshire pig, and wounds were imaged with SFDI/LSI starting immediately after-burn and then daily for the next 4 days. In addition, on each day the burn wounds were biopsied for histological analysis of burn depth, defined by collagen coagulation, apoptosis, and adnexal/vascular necrosis. Histological results show that collagen coagulation progressed from day 0 to day 1, and then stabilized. Results of burn wound imaging using non-invasive techniques were able to produce metrics that correlate to different predictors of burn depth. Collagen coagulation and apoptosis correlated with SFDI scattering coefficient parameter [Formula: see text] and adnexal/vascular necrosis on the day of burn correlated with blood flow determined by LSI. Therefore, incorporation of SFDI scattering coefficient and blood flow determined by LSI may provide an algorithm for accurate assessment of the severity of burn wounds in real time.

  16. New Imaging Methods for Non-invasive Assessment of Mechanical, Structural, and Biochemical Properties of Human Achilles Tendon: A Mini Review

    PubMed Central

    Fouré, Alexandre

    2016-01-01

    The mechanical properties of tendon play a fundamental role to passively transmit forces from muscle to bone, withstand sudden stretches, and act as a mechanical buffer allowing the muscle to work more efficiently. The use of non-invasive imaging methods for the assessment of human tendon's mechanical, structural, and biochemical properties in vivo is relatively young in sports medicine, clinical practice, and basic science. Non-invasive assessment of the tendon properties may enhance the diagnosis of tendon injury and the characterization of recovery treatments. While ultrasonographic imaging is the most popular tool to assess the tendon's structural and indirectly, mechanical properties, ultrasonographic elastography, and ultra-high field magnetic resonance imaging (UHF MRI) have recently emerged as potentially powerful techniques to explore tendon tissues. This paper highlights some methodological cautions associated with conventional ultrasonography and perspectives for in vivo human Achilles tendon assessment using ultrasonographic elastography and UHF MRI. PMID:27512376

  17. Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo

    PubMed Central

    Czarnota, G J; Kolios, M C; Abraham, J; Portnoy, M; Ottensmeyer, F P; Hunt, J W; Sherar, M D

    1999-01-01

    A new non-invasive method for monitoring apoptosis has been developed using high frequency (40 MHz) ultrasound imaging. Conventional ultrasound backscatter imaging techniques were used to observe apoptosis occurring in response to anticancer agents in cells in vitro, in tissues ex vivo and in live animals. The mechanism behind this ultrasonic detection was identified experimentally to be the subcellular nuclear changes, condensation followed by fragmentation, that cells undergo during apoptosis. These changes dramatically increase the high frequency ultrasound scattering efficiency of apoptotic cells over normal cells (25- to 50-fold change in intensity). The result is that areas of tissue undergoing apoptosis become much brighter in comparison to surrounding viable tissues. The results provide a framework for the possibility of using high frequency ultrasound imaging in the future to non-invasively monitor the effects of chemotherapeutic agents and other anticancer treatments in experimental animal systems and in patients. © 1999 Cancer Research Campaign PMID:10507779

  18. Reproducibility of Non-Invasive Assessment of Skin Endothelial Function Using Laser Doppler Flowmetry and Laser Speckle Contrast Imaging

    PubMed Central

    Puissant, Cyril; Abraham, Pierre; Durand, Sylvain; Humeau-Heurtier, Anne; Faure, Sébastien; Lefthériotis, Georges; Rousseau, Pascal; Mahé, Guillaume

    2013-01-01

    Background Endothelial dysfunction precedes atherosclerosis. Vasodilation induced by acetylcholine (ACh) is a specific test of endothelial function. Reproducibility of laser techniques such as laser-Doppler-flowmetry (LDF) and Laser-speckle-contrast-imaging (LSCI) to detect ACh vasodilation is debated and results expressions lack standardization. We aimed to study at a 7-day interval (i) the inter-subject reproducibility, (ii) the intra-subjects reproducibility, and (iii) the effect of the results expressions over variability. Methods and Results Using LDF and LSCI simultaneously, we performed two different ACh-iontophoresis protocols. The maximal ACh vasodilation (peak-ACh) was expressed as absolute or normalized flow or conductance values. Inter-subject reproducibility was expressed as coefficient of variation (inter-CV,%). Intra-subject reproducibility was expressed as within subject coefficients of variation (intra-CV,%), and intra-class correlation coefficients (ICC). Fifteen healthy subjects were included. The inter-subject reproducibility of peak-ACh depended upon the expression of the results and ranged from 55% to 162% for LDF and from 17% to 83% for LSCI. The intra-subject reproducibility (intra-CV/ICC) of peak-ACh was reduced when assessed with LSCI compared to LDF no matter how the results were expressed and whatever the protocol used. The highest intra-subject reproducibility was found using LSCI. It was 18.7%/0.87 for a single current stimulation (expressed as cutaneous vascular conductance) and 11.4%/0.61 for multiple current stimulations (expressed as absolute value). Conclusion ACh-iontophoresis coupled with LSCI is a promising test to assess endothelial function because it is reproducible, safe, and non-invasive. N°: NCT01664572. PMID:23620742

  19. Fluorescence lifetime FRET non-invasive imaging of breast cancer xenografts provides a measure of target engagement in vivo (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Rudkouskaya, Alena; Sinsuebphon, Nattawut; Intes, Xavier; Barroso, Margarida

    2017-02-01

    Fluorescence Lifetime Förster Resonance Energy Transfer (FLIM-FRET) is a unique non-invasive imaging platform to monitor and quantify in vivo target engagement in pre-clinical studies. FLIM FRET is a valuable tool in targeted drug delivery due to its nanoscale-range molecular resolution that detects near-infrared labeled ligand binding to dimerized receptors followed by their uptake into cancer cells in vivo. Various imaging platforms, including PET, lack the ability to directly discriminate between unbound and internalized ligands. Since transferrin receptor (TfR) level is significantly elevated in cancer cells compared to non-cancerous cells, transferrin (Tf) has been successfully used in molecular imaging and targeted anti-cancer drug delivery. The dimeric nature of TfR allows for the quantification of Tf internalization into cancer cells by measuring FLIM FRET between receptor-bound Tf donor and acceptor NIR fluorophore pairs, based on the reduction of donor fluorophore lifetime in live mice. We analyzed tumor morphology, the level of expression of TfR, estrogen receptor (ER) and Tf accumulation in human breast cancer tumor xenografts. We found a remarkable heterogeneity of breast cancer tumors regarding their size, cell density, TfR and ER expression and Tf uptake. The results of this study confirm a strong correlation between in vivo NIR FLIM FRET and ex vivo evaluation of Tf uptake into tumor tissues, thus validating FD% as a robust measure of the target engagement of TfR-Tf in tumor cells in vivo.

  20. A Biocompatible In Vivo Ligation Reaction and its Application for Non-Invasive Bioluminescent Imaging of Protease Activity in Living Mice

    PubMed Central

    Godinat, Aurélien; Park, Hyo Min; Miller, Stephen C.; Cheng, Ke; Hanahan, Douglas; Sanman, Laura E.; Bogyo, Matthew; Yu, Allen; Nikitin, Gennady F.; Stahl, Andreas; Dubikovskaya, Elena A.

    2013-01-01

    The discovery of biocompatible reactions has had a tremendous impact on chemical biology, allowing the study of numerous biological processes directly in complex systems. However, despite the fact that multiple biocompatible reactions have been developed in the past decade, very few work well in living mice. Here we report that D-cysteine and 2-cyanobenzothiazoles can selectively react with each other in vivo to generate a luciferin substrate for firefly luciferase. The success of this “split luciferin” ligation reaction has important implications for both in vivo imaging and biocompatible labeling strategies. First, the production of a luciferin substrate can be visualized in a live mouse by bioluminescence imaging (BLI), and furthermore allows interrogation of targeted tissues using a “caged” luciferin approach. We therefore applied this reaction to the real-time non-invasive imaging of apoptosis associated with caspase 3/7. Caspase-dependent release of free D-cysteine from the caspase 3/7 peptide substrate Asp-Glu-Val-Asp-D-Cys (DEVD-(D-Cys)) allowed selective reaction with 6-amino-2-cyanobenzothiazole (NH2-CBT) in vivo to form 6-amino-D-luciferin with subsequent light emission from luciferase. Importantly, this strategy was found to be superior to the commercially-available DEVD-aminoluciferin substrate for imaging of caspase 3/7 activity. Moreover, the split luciferin approach enables the modular construction of bioluminogenic sensors, where either or both reaction partners could be caged to report on multiple biological events. Lastly, the luciferin ligation reaction is three orders of magnitude faster than Staudinger ligation suggesting further applications for both bioluminescence and specific molecular targeting in vivo. PMID:23463944

  1. Molecular characterization and antibiotic resistance of group G streptococci in Israel: comparison of invasive, non-invasive and carriage isolates.

    PubMed

    Halperin, T; Levine, H; Korenman, Z; Burstein, S; Amber, R; Sela, T; Valinsky, L

    2016-10-01

    Beta-hemolytic group G streptococci (GGS) are increasingly recognized as a source of substantial morbidity, causing mild to severe sporadic infections as well as outbreaks. The purpose of this study was to determine the genetic diversity and antibiotic resistance of GGS in Israel in order to aid in prevention and control. A total of 325 GGS isolates were collected in Israel between 2007 and 2011 from three determined settings: (1) carriage (n = 60), an observational longitudinal carriage study in the IF, (2) non-invasive (n = 166), clinical sporadic and epidemic non-invasive cases in the IDF, and (3) invasive (n = 99) cases of bacteremia collected during this period in Israel from a similar age group, at the national Streptococcal Reference Center. All isolates were characterized genetically and by their antibiotic-resistance profile. emm typing revealed 35 distinct types and subtypes among 228 S. dysgalactiae subsp. equisimilis (SDSE) isolates, with high genetic diversity. An additional 97 GGS were identified as Streptococcus anginosus (SAG). The proportion of SDSE was higher in the invasive (100 %) and non-invasive (63.8 %) isolates compared to the carriage ones (38.3 %). Clindamycin, erythromycin, azithromycin and tetracycline resistance was detected in 6.6 %, 8.6 %, 9.7 % and 37.6 % of isolates, respectively. Overall, the most resistant isolates were in the invasive group and the fewest were in the SAG group. Considerable genetic diversity and common antibiotic resistance were revealed among GGS strains which differed according to the epidemiologic settings. Further clinical, epidemiological and basic research of GGS as a pathogen is warranted.

  2. Non-invasive determination of left ventricular workload in patients with aortic stenosis using magnetic resonance imaging and Doppler echocardiography.

    PubMed

    Keshavarz-Motamed, Zahra; Garcia, Julio; Gaillard, Emmanuel; Capoulade, Romain; Le Ven, Florent; Cloutier, Guy; Kadem, Lyes; Pibarot, Philippe

    2014-01-01

    Early detection and accurate estimation of aortic stenosis (AS) severity are the most important predictors of successful long-term outcomes in patients. Current clinical parameters used for evaluation of the AS severity have several limitations including flow dependency. Estimation of AS severity is specifically challenging in patients with low-flow and low transvalvular pressure gradient conditions. A proper diagnosis in these patients needs a comprehensive evaluation of the left ventricle (LV) hemodynamic loads. This study has two objectives: (1) developing a lumped-parameter model to describe the ventricular-valvular-arterial interaction and to estimate the LV stroke work (SW); (2) introducing and validating a new index, the normalized stroke work (N-SW), to assess the global hemodynamic load imposed on the LV. N-SW represents the global hemodynamic load that the LV faces for each unit volume of blood ejected. The model uses a limited number of parameters which all can be measured non-invasively using current clinical imaging modalities. The model was first validated by comparing its calculated flow waveforms with the ones measured using Cardiovascular Magnetic Resonance (CMR) in 49 patients and 8 controls. A very good correlation and concordance were found throughout the cycle (median root mean square: 12.21 mL/s) and between the peak values (r = 0.98; SEE = 0.001, p<0.001). The model was then used to determine SW using the parameters measured with transthoracic Doppler-echocardiography (TTE) and CMR. N-SW showed very good correlations with a previously-validated index of global hemodynamic load, the valvular arterial impedance ([Formula: see text]), using data from both imaging modalities (TTE: r = 0.82, SEE = 0.01, p<0.001; CMR: r = 0.74, SEE = 0.01, p<0.001). Furthermore, unlike , N-SW was almost independent from variations in the flow rate. This study suggests that considering N-SW may provide incremental diagnostic and prognostic information, beyond what

  3. A double-blind controlled clinical trial assessing the effect of topical gels on striae distensae (stretch marks): a non-invasive imaging, morphological and immunohistochemical study.

    PubMed

    Ud-Din, Sara; McAnelly, Sarah-Louise; Bowring, Alison; Whiteside, Sigrid; Morris, Julie; Chaudhry, Iskander; Bayat, Ardeshir

    2013-09-01

    Striae distensae (SD) are cutaneous lesions often presenting post-pregnancy with atrophy and flattening of the epidermis. SD is poorly understood and treatment remains ill-defined. Our aim was to assess the effect of topical application of silicone gel compared with placebo on SD using non-invasive devices and by immunohistochemical analysis of sequential tissue biopsies in a double-blind controlled trial. Twenty volunteers massaged silicone and placebo gels into separate sides of the abdomen, daily for 6 weeks. Objective non-invasive imaging plus subjective self-assessment of SD were performed on days 0, 21, 42, 90, in addition to tissue biopsies on days 0 and 42. Non-invasive imaging demonstrated an increase in melanin and a decrease in haemoglobin, collagen and pliability over the 6-week period on both sides. Additionally, collagen levels in SD were significantly higher (p value = 0.001) and melanin levels lower (p value = 0.048) with silicone gel compared with placebo. Histological analysis revealed epidermal flattening with a reduction of rete ridges in SD on both sides. Vascular count significantly decreased with placebo gel (p = 0.002). Corroborating the clinical results, melanin levels increased, whilst collagen type 1 and elastin decreased on both sides. Non-invasive techniques showed that the application of silicone gel increased collagen levels and reduced pigmentation compared with placebo. However, both clinical and histological data revealed that melanin increased whilst collagen, elastin and pliability decreased over the 6-week period with both gels. Furthermore, vascularity significantly decreased with placebo gel. These findings provide preliminary evidence of the utility of topical gels in the clinical management of SD.

  4. Molecular and structural characterization of some violet phosphate pigments for their non-invasive identification in modern paintings

    NASA Astrophysics Data System (ADS)

    Anselmi, C.; Vagnini, M.; Cartechini, L.; Grazia, C.; Vivani, R.; Romani, A.; Rosi, F.; Sgamellotti, A.; Miliani, C.

    2017-02-01

    A complete non-invasive characterization by XRF, XRD, near-FTIR and UV-Vis reflectance spectroscopy has been performed on some commercially available violet pigments as well as on pure violet Co-salts also known to be used as pigments. The obtained results show that, after a preliminary elemental characterization, the studied pigments can be easily identified by near-FTIR and UV-Vis spectroscopies since they exhibit peculiar spectral bands in these regions. Among the analyzed samples emerged that the pigment 45350 - "Manganviolett" from Kremer consists of two α- and β-NH4MnP2O7 polymorphs, being α-NH4MnP2O7 the most abundant one; furthermore we found that the pigment R1215D -"Cobalt violet" by Winsor & Newton (no longer available since 2006) displays spectral features that match exactly those of 45820-"Kobaltviolett hell" from Kremer and both are composed by cobalt ammonium phosphate hydrate. Such non-invasive study allowed for the identification of "Manganese Violet" (α-NH4MnP2O7) and anhydrous cobalt phosphate (Co3(PO4)2) on some Boccioni's paintings during MOLAB in situ measurements at the Museo del Novecento (Milano). The spectrum of sample 6 shows, as expected, the O-P-O bending and P-O stretching vibrational multiple bands in the ranges of 420-700 cm-1 and 1000-1250 cm-1, while the peaks located at 760 and 912 cm-1 are attributed to the symmetric and antisymmetric P-O-P vibrations that are typical of the pyrophosphate group. [4]. Characteristic stretching and bending absorptions of the NH4+ cation are visible in the range 3300-3000 cm-1, and at about 1450-1400 cm-1. Typical spectral features of kaolin are visible at 3620 and 3694 cm-1[5].

  5. PET-based molecular imaging in neuroscience.

    PubMed

    Jacobs, A H; Li, H; Winkeler, A; Hilker, R; Knoess, C; Rüger, A; Galldiks, N; Schaller, B; Sobesky, J; Kracht, L; Monfared, P; Klein, M; Vollmar, S; Bauer, B; Wagner, R; Graf, R; Wienhard, K; Herholz, K; Heiss, W D

    2003-07-01

    Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

  6. [Non-invasive trans-cranial magnetic resonance imaging-guided focused ultrasounds surgery to treat neurologic disorders].

    PubMed

    Gagliardo, Cesare; Geraci, Laura; Napoli, Alessandro; Giugno, Antonella; Cortegiani, Andrea; Canzio, Danilo; Giarratano, Antonello; Franzini, Angelo; Iacopino, Domenico Gerardo; Catalano, Carlo; Midiri, Massimo

    2016-05-01

    In past years non-invasive clinical applications of magnetic resonance-guided focused ultrasound for the treatment of neurological disorders have been hampered by technical limitations that today have been finally overcome. In 2015, for the first time in the world, the very first treatments have been performed in Italy by the use of an affordable 1.5T magnetic resonance unit. The clinical results obtained to date and all the future possible applications are very promising and pave the way towards safe and effective treatment options once unthinkable.

  7. Non-Invasive In Vivo Imaging and Quantification of Tumor Growth and Metastasis in Rats Using Cells Expressing Far-Red Fluorescence Protein.

    PubMed

    Christensen, Jon; Vonwil, Daniel; Shastri, V Prasad

    2015-01-01

    Non-invasive in vivo imaging is emerging as an important tool for basic and preclinical research. Near-infrared (NIR) fluorescence dyes and probes have been used for non-invasive optical imaging since in the NIR region absorption and auto fluorescence by body tissue is low, thus permitting for greater penetration depths and high signal to noise ratio. Currently, cell tracking systems rely on labeling cells prior to injection or administering probes targeting the cell population of choice right before imaging. These approaches do not enable imaging of tumor growth, as the cell label is diluted during cell division. In this study we have developed cell lines stably expressing the far-red fluorescence protein E2-Crimson, thus enabling continuous detection and quantification of tumor growth. In a xenograft rat model, we show that E2-Crimson expressing cells can be detected over a 5 week period using optical imaging. Fluorescence intensities correlated with tumor volume and weight and allowed for a reliable and robust quantification of the entire tumor compartment. Using a novel injection regime, the seeding of MDA-MB-231 breast cancer cells in the lungs in a rat model was established and verified.

  8. Non-invasive vascular radial/circumferential strain imaging and wall shear rate estimation using video images of diagnostic ultrasound.

    PubMed

    Wan, Jinjin; He, Fangli; Zhao, Yongfeng; Zhang, Hongmei; Zhou, Xiaodong; Wan, Mingxi

    2014-03-01

    The aim of this work was to develop a convenient method for radial/circumferential strain imaging and shear rate estimation that could be used as a supplement to the current routine screening for carotid atherosclerosis using video images of diagnostic ultrasound. A reflection model-based correction for gray-scale non-uniform distribution was applied to B-mode video images before strain estimation to improve the accuracy of radial/circumferential strain imaging when applied to vessel transverse cross sections. The incremental and cumulative radial/circumferential strain images can then be calculated based on the displacement field between consecutive B-mode images. Finally, the transverse Doppler spectra acquired at different depths along the vessel diameter were used to construct the spatially matched instantaneous wall shear values in a cardiac cycle. Vessel phantom simulation results revealed that the signal-to-noise ratio and contrast-to-noise ratio of the radial and circumferential strain images were increased by 2.8 and 5.9 dB and by 2.3 and 4.4 dB, respectively, after non-uniform correction. Preliminary results for 17 patients indicated that the accuracy of radial/circumferential strain images was improved in the lateral direction after non-uniform correction. The peak-to-peak value of incremental strain and the maximum cumulative strain for calcified plaques are evidently lower than those for other plaque types, and the echolucent plaques had higher values, on average, than the mixed plaques. Moreover, low oscillating wall shear rate values, found near the plaque and stenosis regions, are closely related to plaque formation. In conclusion, the method described can provide additional valuable results as a supplement to the current routine ultrasound examination for carotid atherosclerosis and, therefore, has significant potential as a feasible screening method for atherosclerosis diagnosis in the future. Copyright © 2014 World Federation for Ultrasound in

  9. Non-invasive assessment of elastic modulus of arterial constructs during cell culture using ultrasound elasticity imaging.

    PubMed

    Dutta, Debaditya; Lee, Kee-Won; Allen, Robert A; Wang, Yadong; Brigham, John C; Kim, Kang

    2013-11-01

    Mechanical strength is a key design factor in tissue engineering of arteries. Most existing techniques assess the mechanical property of arterial constructs destructively, leading to sacrifice of a large number of animals. We propose an ultrasound-based non-invasive technique for the assessment of the mechanical strength of engineered arterial constructs. Tubular scaffolds made from a biodegradable elastomer and seeded with vascular fibroblasts and smooth muscle cells were cultured in a pulsatile-flow bioreactor. Scaffold distension was computed from ultrasound radiofrequency signals of the pulsating scaffold via 2-D phase-sensitive speckle tracking. Young's modulus was then calculated by solving the inverse problem from the distension and the recorded pulse pressure. The stiffness thus computed from ultrasound correlated well with direct mechanical testing results. As the scaffolds matured in culture, ultrasound measurements indicated an increase in Young's modulus, and histology confirmed the growth of cells and collagen fibrils in the constructs. The results indicate that ultrasound elastography can be used to assess and monitor non-invasively the mechanical properties of arterial constructs. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  10. Non-invasive Assessment of Elastic Modulus of Arterial Constructs during Cell Culture using Ultrasound Elasticity Imaging

    PubMed Central

    Dutta, Debaditya; Lee, Kee-Won; Allen, Robert A.; Wang, Yadong; Brigham, John C.; Kim, Kang

    2013-01-01

    Mechanical strength is a key design factor for engineered arteries. Most existing techniques assess the mechanical property of arterial constructs destructively, leading to a large number of animal sacrifices. We propose an ultrasound-based non-invasive mechanical strength assessment technique for engineered arterial constructs. Tubular scaffolds made from a biodegradable elastomer and seeded with vascular fibroblasts and smooth muscle cells were cultured in a pulsatile-flow bioreactor. Scaffold distension was computed from ultrasound radiofrequency signals of the pulsating scaffold via two-dimensional phase-sensitive speckle tracking. The Young's modulus was then calculated by solving inverse problem from the distension and the recorded pulse pressure. Stiffness thus computed from ultrasound correlated well with direct mechanical testing results. As the scaffolds matured in culture, ultrasound measurements showed increased Young's modulus and histology confirmed the growth of cells and collagen fibrils in the constructs. The results show that ultrasound elastography non-invasively assesses and monitors the mechanical properties of arterial constructs. PMID:23932282

  11. Thermal imaging is a non-invasive alternative to PET-CT for measurement of brown adipose tissue activity in humans.

    PubMed

    Law, James Matthew; Morris, David Edward; Engbeaya, Chioma Izzi; Salem, Victoria; Coello, Christopher; Robinson, Lindsay; Jayasinghe, Maduka; Scott, Rebecca; Gunn, Roger; Rabiner, Eugenii; Tan, Tricia; Dhillo, Waljit; Bloom, Stephen; Budge, Helen; Symonds, Michael

    2017-09-14

    Background: Obesity and its metabolic consequences are a major cause of morbidity and mortality. Brown adipose tissue (BAT) utilises glucose and free fatty acids to produce heat, thereby increasing energy expenditure. Effective evaluation of human BAT stimulators is constrained by current standard BAT assessment methods as positron emission tomography-computed tomography (PET-CT) requires exposure to high doses of ionising radiation. Infrared thermography (IRT) is a potential non-invasive, safe alternative, although direct corroboration with PET-CT has not previously been established. Methods: IRT and (18)F-FDG PET-CT data from 8 healthy male participants subjected to water jacket cooling were directly compared. Thermal images (TIs) were geometrically transformed to overlay PET-CT-derived maximum intensity projection (MIP) images from each subject and the areas of greatest intensity of temperature and glucose-uptake within the supraclavicular regions compared. Relationships between supraclavicular temperatures from IRT (TSCR) and the maximum rate of glucose uptake (MR(gluc)) from PET-CT were determined. Results: Glucose uptake on MR(gluc)MIP was positively correlated with change in TSCR relative to a reference region (r2 = 0.721; P = 0.008). Spatial overlap between areas of maximal MR(gluc)MIP and maximal TSCR was 29.5±5.1%. Prolonged cooling to 60 minutes was associated with further TSCR rise compared with cooling to 10 minutes. Conclusion: The supraclavicular hotspot identified on IRT closely corresponds to the area of maximal uptake on PET-CT-derived MR(gluc)MIP images. Greater increases in relative TSCR were associated with raised glucose uptake. IRT should now be considered a suitable method for measuring BAT activation, especially in populations where PET-CT is not feasible, practical or repeatable.

  12. Feature tracking cardiac magnetic resonance imaging: A review of a novel non-invasive cardiac imaging technique

    PubMed Central

    Rahman, Zia Ur; Sethi, Pooja; Murtaza, Ghulam; Virk, Hafeez Ul Hassan; Rai, Aitzaz; Mahmod, Masliza; Schoondyke, Jeffrey; Albalbissi, Kais

    2017-01-01

    Cardiovascular disease is a leading cause of morbidity and mortality globally. Early diagnostic markers are gaining popularity for better patient care disease outcomes. There is an increasing interest in noninvasive cardiac imaging biomarkers to diagnose subclinical cardiac disease. Feature tracking cardiac magnetic resonance imaging is a novel post-processing technique that is increasingly being employed to assess global and regional myocardial function. This technique has numerous applications in structural and functional diagnostics. It has been validated in multiple studies, although there is still a long way to go for it to become routine standard of care. PMID:28515849

  13. Non-invasive Florentine Renaissance Panel Painting Replica Structures Investigation by Using Terahertz Time-Domain Imaging (THz-TDI) Technique

    NASA Astrophysics Data System (ADS)

    Koch Dandolo, Corinna L.; Picollo, Marcello; Cucci, Costanza; Jepsen, Peter Uhd

    2016-11-01

    The potentials of the Terahertz Time-Domain Imaging (THz-TDI) technique for a non-invasive inspection of panel paintings have been considered in detail. The THz-TD data acquired on a replica of a panel painting made in imitation of Italian Renaissance panel paintings were processed in order to provide insights as to the limits and potentials of the technique in detecting different kinds of underdrawings and paint layers. Constituent layers, construction techniques, and anomalies were identified and localized by interpreting the extracted THz dielectric stratigraphy.

  14. Non-invasive measurements of granular flows by magnetic resonance imaging. Technical progress report for the quarter ending December 31, 1992

    SciTech Connect

    Nakagawa, M.; Altobelli, S.A.; Caprihan, A.; Fukushima, E.; Jeong, E.K.

    1993-01-20

    Magnetic Resonance Imaging (MRI) was used to measure granular-flow in a partially filled, steadily rotating, long, horizontal cylinder. This non-invasive technique can yield statistically averaged two-dimensional concentrations and velocity profiles anywhere in the flow of suitable granular materials. First, rigid body motion of a cylinder fill with granular material was studied to confirm the validity of this method. Then, the density variation of the flowing layer where particles collide and dilate, and the depth of the flowing layer and the flow velocity profile were obtained as a function of the cylinder rotation rate.

  15. IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma.

    PubMed

    Kickingereder, Philipp; Sahm, Felix; Radbruch, Alexander; Wick, Wolfgang; Heiland, Sabine; Deimling, Andreas von; Bendszus, Martin; Wiestler, Benedikt

    2015-11-05

    The recent identification of IDH mutations in gliomas and several other cancers suggests that this pathway is involved in oncogenesis; however effector functions are complex and yet incompletely understood. To study the regulatory effects of IDH on hypoxia-inducible-factor 1-alpha (HIF1A), a driving force in hypoxia-initiated angiogenesis, we analyzed mRNA expression profiles of 288 glioma patients and show decreased expression of HIF1A targets on a single-gene and pathway level, strong inhibition of upstream regulators such as HIF1A and downstream biological functions such as angio- and vasculogenesis in IDH mutant tumors. Genotype/imaging phenotype correlation analysis with relative cerebral blood volume (rCBV) MRI - a robust and non-invasive estimate of tumor angiogenesis - in 73 treatment-naive patients with low-grade and anaplastic gliomas showed that a one-unit increase in rCBV corresponded to a two-third decrease in the odds for an IDH mutation and correctly predicted IDH mutation status in 88% of patients. Together, these findings (1) show that IDH mutation status is associated with a distinct angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging and (2) highlight the potential future of radiogenomics (i.e. the correlation between cancer imaging and genomic features) towards a more accurate diagnostic workup of brain tumors.

  16. Non-invasive temperature assessment at different tissue types based on average grey-level from B-mode ultrasonic images

    NASA Astrophysics Data System (ADS)

    Alvarenga, A. V.; Teixeira, C. A.; Von Krüger, M. A.; Pereira, W. C. A.

    2012-05-01

    The average grey-levels calculated from B-Mode images were assessed for non-invasive temperature estimation in a porcine tissue sample containing two different tissue types, fat and muscle. The porcine sample was subjected to heating and cooling procedures with temperature varying from 35°C to 42°C. The sample was continuously imaged with an ultrasound scanner, and simultaneously the temperature was measured at each 5 seconds using Type-T thermocouples. The result shows that the average grey-level (AVGL)/temperature relations are different for the two studied regions, where the muscle tissue tends to present a bigger AVGL variation than the fat tissue considering the same temperature variation. Besides, the average grey-level/temperature functions estimated for each tissue region presented fitting errors inferior to ± 0.21°C, indicating that it might be possible to track temperature changes from both tissues using AVGL. This result is innovative since it suggests that using the same B-mode image and an average grey-level/temperature function to each region it is possible to estimate non-invasively temperature variations from different tissue regions in the same tissue sample. Future work includes the investigation of the spatial limits of these average grey-level/temperature functions.

  17. Self-assembled dual-modality contrast agents for non-invasive stem cell tracking via near-infrared fluorescence and magnetic resonance imaging.

    PubMed

    Liu, Hong; Tan, Yan; Xie, Lisi; Yang, Lei; Zhao, Jing; Bai, Jingxuan; Huang, Ping; Zhan, Wugen; Wan, Qian; Zou, Chao; Han, Yali; Wang, Zhiyong

    2016-09-15

    Stem cells hold great promise for treating various diseases. However, one of the main drawbacks of stem cell therapy is the lack of non-invasive image-tracking technologies. Although magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging have been employed to analyse cellular and subcellular events via the assistance of contrast agents, the sensitivity and temporal resolution of MRI and the spatial resolution of NIRF are still shortcomings. In this study, superparamagnetic iron oxide nanocrystals and IR-780 dyes were co-encapsulated in stearic acid-modified polyethylenimine to form a dual-modality contrast agent with nano-size and positive charge. These resulting agents efficiently labelled stem cells and did not influence the cellular viability and differentiation. Moreover, the labelled cells showed the advantages of dual-modality imaging in vivo.

  18. Non-invasive characterization of normal and pathological tissues through dynamic infrared imaging in the hamster cheek pouch oral cancer model

    NASA Astrophysics Data System (ADS)

    Herrera, María. S.; Monti Hughes, Andrea; Salva, Natalia; Padra, Claudio; Schwint, Amanda; Santa Cruz, Gustavo A.

    2017-05-01

    Biomedical infrared thermography, a non-invasive and functional imaging method, provides information on the normal and abnormal status and response of tissues in terms of spatial and temporal variations in body infrared radiance. It is especially attractive in cancer research due to the hypervascular and hypermetabolic activity of solid tumors. Moreover, healthy tissues like skin or mucosa exposed to radiation can be examined since inflammation, changes in water content, exudation, desquamation, erosion and necrosis, between others, are factors that modify their thermal properties. In this work we performed Dynamic Infrared Imaging (DIRI) to contribute to the understanding and evaluation of normal tissue, tumor and precancerous tissue response and radiotoxicity in an in vivo model, the hamster cheek pouch, exposed to Boron Neutron Capture Therapy. In this study, we particularly focused on the observation of temperature changes under forced transient conditions associated with mass moisture transfer in the tissue-air interface, in each tissue with or without treatment. We proposed a simple mathematical procedure that considerers the heat transfer from tissue to ambient through convection and evaporation to model the transient (exponential decay o recover) thermal study. The data was fitted to determined the characteristic decay and recovery time constants of the temperature as a function of time. Also this model allowed to explore the mass flux of moisture, as a degree of evaporation occurring on the tissue surface. Tissue thermal responses under provocation tests could be used as a non-invasive method to characterize tissue physiology.

  19. Identification of Two Distinct Molecular Subtypes of Non-Invasive Follicular Neoplasm with Papillary-Like Nuclear Features by Digital RNA Counting.

    PubMed

    Giannini, Riccardo; Ugolini, Clara; Poma, Anello Marcello; Urpì, Maria; Niccoli, Cristina; Elisei, Rossella; Chiarugi, Massimo; Vitti, Paolo; Miccoli, Paolo; Basolo, Fulvio

    2017-10-01

    The follicular variant (FV) of papillary thyroid cancer (PTC) is one of the most common variants of PTC. Clinically, non-infiltrative FVPTC is considered a low-risk variant of PTC, and the non-invasive encapsulated forms of FVPTC represent a group of thyroid tumors with a particularly good prognosis. Consequently, these neoplasms have been very recently reclassified as non-invasive follicular neoplasms with papillary-like nuclear features (NIFTP). From a molecular standpoint, NIFTP appears to be similar to follicular neoplasms. However, only limited data are currently available regarding their gene expression profile. The aim of this study was to identify specific molecular signatures of 26 NIFTPs compared to those of 19 follicular adenomas (FAs) and 18 infiltrative FVPTCs (IFVPTCs). A nanoString custom assay was used to perform mRNA expression analysis. All cases were also genotyped for BRAF, N-, H-, and K-RAS mutations. Samples were grouped on the basis of gene expression profiles by Pearson's correlation and non-negative matrix factorization clustering analysis. Finally, the uncorrelated shrunken centroid machine-learning algorithm was used to classify the samples. The results revealed distinct expression profiles of FAs and IFVPTCs. NIFTP samples can exhibit different expression profiles, more similar to FAs (FA-like) or to IFVPTCs (IFVPTC-like), and these different expression profiles largely depend on the presence of different mutations (RAS or BRAF). In conclusion, although further validation of the model is required by using a larger group of prospective cases, these data reinforce the hypothesis that IFVPTC-like NIFTPs might represent precursors of IFVPTC.

  20. A Biocompatible “Split Luciferin” Reaction and its Application for Non-Invasive Bioluminescent Imaging of Protease Activity in Living Animals

    PubMed Central

    Godinat, Aurélien; Budin, Ghyslain; Molares, Alma R.; Park, Hyo Min; Sanman, Laura E.; Bogyo, Matthew; Yu, Allen; Stahl, Andreas; Dubikovskaya, Elena A.

    2014-01-01

    The great complexity of many human pathologies such as cancer, diabetes, and neurodegenerative diseases requires new tools for studies of biological processes on the whole organism level. The discovery of novel biocompatible reactions has tremendously advanced our understanding of basic biology, however, no efficient tools exist for real-time non-invasive imaging of many human proteases that play very important roles in multiple human disorders. We recently reported that “split luciferin” biocompatible reaction represents a valuable tool for evaluation of protease activity directly in living animals using bioluminescence imaging (BLI). Since BLI is the most sensitive in vivo imaging modality known to date, this method can be widely applied for the evaluation of multiple proteases activity as well as identification of their new peptide-specific substrates. In this protocol we describe several applications of this “split luciferin” reaction for quantification of protease activities in test tube assays and living animals. PMID:25205565

  1. Non-invasive image-guided laser microsurgery by a dual-wavelength fiber laser and an integrated fiber-optic multi-modal system.

    PubMed

    Tsai, Meng-Tsan; Li, Dean-Ru; Chan, Ming-Che

    2016-10-15

    A new approach to non-invasive image-guided laser micro-treatment is demonstrated by a dual-wavelength fiber laser source and an integrated fiber-based multi-modal system. The fiber-based source, operated in 1.55 and 1.2 μm simultaneously, was directly connected to an integrated fiber-based multi-modal system for imaging and laser micro-treatment at the same time. The 1.2 μm radiations, within the 1.2-1.35 μm bio-penetration window of skin, were utilized for spectral domain optical coherence tomography imaging. The 1.55 μm radiations, highly absorptive to waters, were utilized for laser microsurgery. The new approach, which is simple in configuration and accurately controls the positions and exposure time of the laser microsurgery, shows great promises for future clinical applications.

  2. Non-invasive imaging of infection after treatment with tumor-homing bacteria using chemical exchange saturation transfer (CEST) MRI

    PubMed Central

    Liu, Guanshu; Bettegowda, Chetan; Qiao, Yuan; Staedtke, Verena; Chan, Kannie W.Y.; Bai, Renyuan; Li, Yuguo; Riggins, Gregory J.; Kinzler, Kenneth W.; Bulte, Jeff W.M.; McMahon, Michael T.; Gilad, Assaf A.; Vogelstein, Bert; Zhou, Shibin; van Zijl, Peter C.M.

    2013-01-01

    Purpose To develop a non-invasive MRI method for determining the germination and infection of tumor-homing bacteria in bacteriolytic cancer therapy using endogenous CEST contrast. Methods The CEST parameters of the anaerobic gram-positive bacterium Clostridium novyi-NT (C. novyi-NT) were first characterized in vitro, then used to detect C. novyi-NT germination and infection in subcutaneous CT26 colorectal tumor-bearing mice (n=6) after injection of 300 million bacterial spores. Lipopolysacharide (LPS) injected mice were used to exclude that the changes of CEST MRI were due to inflammation. Results CEST contrast was observed over a broad frequency range for bacterial suspensions in vitro, with the maximum contrast around 2.6 ppm from the water resonance. No signal could be detected for bacterial spores, demonstrating the specificity for germination. In vivo, a significant elevation of CEST contrast was identified in C. novyi-NT infected tumors as compared to those before bacterial germination and infection (p<0.05, n=6). No significant change was observed in tumors with LPS-induced sterile inflammation (p> 0.05, n=4). Conclusions Endogenous bacterial CEST contrast (bacCEST) can be used to monitor the germination and proliferation of the therapeutic bacterium C. novyi-NT without a need for exogenous cell labeling probes. PMID:24123389

  3. Non-invasive volumetric optoacoustic imaging of cardiac cycles in acute myocardial infarction model in real-time

    NASA Astrophysics Data System (ADS)

    Lin, Hasiao-Chun Amy; Déan-Ben, Xosé Luís.; Kimm, Melanie; Kosanke, Katja; Haas, Helena; Meier, Reinhard; Lohöfer, Fabian; Wildgruber, Moritz; Razansky, Daniel

    2017-03-01

    Extraction of murine cardiac functional parameters on a beat-by-beat basis remains challenging with the existing imaging modalities. Novel methods enabling in vivo characterization of functional parameters at a high temporal resolution are poised to advance cardiovascular research and provide a better understanding of the mechanisms underlying cardiac diseases. We present a new approach based on analyzing contrast-enhanced optoacoustic (OA) images acquired at high volumetric frame rate without using cardiac gating or other approaches for motion correction. Acute myocardial infarction was surgically induced in murine models, and the method was modified to optimize for acquisition of artifact-free optoacoustic data. Infarcted hearts could be differentiated from healthy controls based on a significantly higher pulmonary transit time (PTT: infarct 2.07 s vs. healthy 1.34 s), while no statistically significant difference was observed in the heart rate (318 bpm vs. 309 bpm). In combination with the proven ability of optoacoustics to track targeted probes within the injured myocardium, our method is capable of depicting cardiac anatomy, function, and molecular signatures on a beat-by-beat basis, both with high spatial and temporal resolution, thus providing new insights into the study of myocardial ischemia.

  4. Non-invasive, photonics-based diagnostic, imaging, monitoring, and light delivery techniques for the recognition, quantification and treatment of malignant and chronic inflammatory conditions

    NASA Astrophysics Data System (ADS)

    Davies, N.; Davies-Shaw, D.; Shaw, J. D.

    2007-02-01

    We report firsthand on innovative developments in non-invasive, biophotonic techniques for a wide range of diagnostic, imaging and treatment options, including the recognition and quantification of cancerous, pre-cancerous cells and chronic inflammatory conditions. These techniques have benefited from the ability to target the affected site by both monochromatic light and broad multiple wavelength spectra. The employment of such wavelength or color-specific properties embraces the fluorescence stimulation of various photosensitizing drugs, and the instigation and detection of identified fluorescence signatures attendant upon laser induced fluorescence (LIF) phenomena as transmitted and propagated by precancerous, cancerous and normal tissue. In terms of tumor imaging and therapeutic and treatment options, we have exploited the abilities of various wavelengths to penetrate to different depths, through different types of tissues, and have explored quantifiable absorption and reflection characteristics upon which diagnostic assumptions can be reliably based and formulated. These biophotonic-based diagnostic, sensing and imaging techniques have also benefited from, and have been further enhanced by, the integrated ability to provide various power levels to be employed at various stages in the procedure. Applications are myriad, including non-invasive, non destructive diagnosis of in vivo cell characteristics and functions; light-based tissue analysis; real-time monitoring and mapping of brain function and of tumor growth; real time monitoring of the surgical completeness of tumor removal during laser-imaged/guided brain resection; diagnostic procedures based on fluorescence life-time monitoring, the monitoring of chronic inflammatory conditions (including rheumatoid arthritis), and continuous blood glucose monitoring in the control of diabetes.

  5. MO-E-BRD-03: Intra-Operative Breast Brachytherapy: Is One Stop Shopping Best? [Non-invasive Image-Guided Breast Brachytherapy

    SciTech Connect

    Libby, B.

    2015-06-15

    Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant. A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current

  6. [Non-invasive investigation of muscle function using 31P magnetic resonance spectroscopy and 1H MR imaging].

    PubMed

    Bendahan, D; Mattei, J P; Guis, S; Kozak-Ribbens, G; Cozzone, P J

    2006-04-01

    31P MRS and 1H MRI of skeletal muscle have become major new tools allowing a complete non invasive investigation of muscle function both in the clinical setting and in basic research. The comparative analysis of normal and diseased muscle remains a major requirement to further define metabolic events surrounding muscle contraction and the metabolic anomalies underlying pathologies. Also, standardized rest-exercise-recovery protocols for the exploration of muscle metabolism by P-31 MRS in healthy volunteers as well as in patients with intolerance to exercise have been developed. The CRMBM protocol is based on a short-term intense exercise, which is very informative and well accepted by volunteers and patients. Invariant metabolic parameters have been defined to characterize the normal metabolic response to the protocol. Deviations from normality can be directly interpreted in terms of specific pathologies in some favorable cases. This protocol has been applied to more than 4,000 patients and healthy volunteers over a period of 15 years. On the other hand, MRI investigations provide anatomical and functional information from resting and exercising muscle. From a diagnostic point of view, dedicated pulse sequences can be used in order to detect and quantify muscle inflammation, fatty replacement, muscle hyper and hypotrophy. In most cases, MR techniques provide valuable information which has to be processed in conjunction with traditional invasive biochemical, electrophysiological and histoenzymological tests. P-31 MRS has proved particularly useful in the therapeutic follow-up of palliative therapies (coenzyme Q treatment of mitochondriopathies) and in family investigations. It is now an accepted diagnostic tool in the array of tests which are used to characterize muscle disorders in clinical routine. As a research tool, it will keep bringing new information on the physiopathology of muscle diseases in animal models and in humans and should play a role in the

  7. Non-invasive vascular modulography method for imaging the local elasticity of atheroscle-rotic plaques: simulation and in vitro vessel phantom study.

    PubMed

    Poree, Jonathan; Chayer, Boris; Soulez, Gilles; Ohayon, Jacques; Cloutier, Guy

    2017-09-28

    Mechanical and morphological characterization of atherosclerotic lesions in carotid arteries remains an essential step for the evaluation of rupture prone plaques and the preven-tion of strokes. In this study, we propose a non-invasive imaging modulography method (NIV-iMod), which is able of reconstruct-ing a heterogeneous Young's modulus distribution of a carotid plaque from the Von Mises strain elastogram. Elastograms were computed with non-invasive ultrasound images using the La-grangian speckle model estimator (LSME) and a dynamic seg-mentation-optimization procedure to highlight mechanical heter-ogeneities. This methodology, based on continuum mechanics, was validated in silico with finite element model (FEM) strain fields and ultrasound simulations, and in vitro with polyvinyl alcohol cryogel phantoms based on magnetic resonance imaging geometries of carotid plaques. In silico, our results show that the NiV-iMod method: i) successfully detected and quantified necrot-ic core inclusions with high positive predictive and sensitivity values of 81 ± 10% and 91 ± 6%, (ii) quantified Young's moduli of necrotic cores, fibrous tissues and calcium inclusions with mean values of 32 ± 23 kPa, 515 ± 30 kPa and 3160 ± 218 kPa (ground true values are 10 kPa, 600 kPa and 5000 kPa), and (iii) overestimated the cap thickness by ~172 μm. In vitro, the positive predictive and sensitivity values for detecting soft inclusions were 60 ± 21% and 88 ± 9%, and Young's modulus mean values of mimicking lipid, fibrosis and calcium were 34 ± 19 kPa, 193 ± 14 kPa and 649 ± 118 kPa (ground true values are 25 ± 3 kPa, 182 ± 21 kPa and 757 ± 87 kPa).

  8. [Molecular imaging].

    PubMed

    Turetschek, K; Wunderbaldinger, P

    2002-01-01

    The disclosure of the human genoma, the progress in understanding of diseases on molecular and cellular levels, the discovery of new disease-specific targets, and the development of new medications will revolutionize our understanding of the etiology and the treatment of many disease entities. Radiologists are faced with a paradigm shift from unspecific to specific molecular imaging techniques as well as with enormous speed in the development of new methods and should be enrolled actively in this field of medicine.

  9. Non-invasive dual fluorescence in vivo imaging for detection of macrophage infiltration and matrix metalloproteinase (MMP) activity in inflammatory arthritic joints.

    PubMed

    Cho, Hongsik; Bhatti, Fazal-Ur-Rehman; Yoon, Tae Won; Hasty, Karen A; Stuart, John M; Yi, Ae-Kyung

    2016-05-01

    Detection and intervention at an early stage is a critical factor to impede arthritis progress. Here we present a non-invasive method to detect inflammatory changes in joints of arthritic mice. Inflammation was monitored by dual fluorescence optical imaging for near-infrared fluorescent (750F) matrix-metalloproteinase activatable agent and allophycocyanin-conjugated anti-mouse CD11b. Increased intensity of allophycocyanin (indication of macrophage accumulation) and 750F (indication of matrix-metalloproteinase activity) showed a biological relationship with the arthritis severity score and the histopathology score of arthritic joints. Our results demonstrate that this method can be used to detect early stages of arthritis with minimum intervention in small animal models.

  10. Non-invasive current and voltage imaging techniques for integrated circuits using scanning probe microscopy. Final report, LDRD Project FY93 and FY94

    SciTech Connect

    Campbell, A.N.; Cole, E.I. Jr.; Tangyunyong, Paiboon

    1995-06-01

    This report describes the first practical, non-invasive technique for detecting and imaging currents internal to operating integrated circuits (ICs). This technique is based on magnetic force microscopy and was developed under Sandia National Laboratories` LDRD (Laboratory Directed Research and Development) program during FY 93 and FY 94. LDRD funds were also used to explore a related technique, charge force microscopy, for voltage probing of ICs. This report describes the technical work performed under this LDRD as well as the outcomes of the project in terms of publications and awards, intellectual property and licensing, synergistic work, potential future work, hiring of additional permanent staff, and benefits to DOE`s defense programs (DP).

  11. Using non-invasive magnetic resonance imaging (MRI) to assess the reduction of Cr(VI) using a biofilm-palladium catalyst.

    PubMed

    Beauregard, D A; Yong, P; Macaskie, L E; Johns, M L

    2010-09-01

    Industrial waste streams may contain contaminants that are valuable like Pd(II) and/or toxic and mutagenic like Cr(VI). Using Serratia sp. biofilm the former was biomineralized to produce a supported nanocrystalline Pd(0) catalyst, and this biofilm-Pd heterogeneous catalyst was then used to reduce Cr(VI) to less dangerous Cr(III) at room temperature, with formate as the electron donor. Cr(VI)((aq)) is non-paramagnetic while Cr(III)((aq)) is paramagnetic, which enabled spatial mapping of Cr species concentrations within the reactor cell using non-invasive magnetic resonance (MR) imaging experiments. Spatial reactivity heterogeneities were thus examined. In batch reactions, these could be attributed primarily to heterogeneity of Pd(0) distribution and to the development of gas bubbles within the reactor. In continuous flow reactions, spatial reactivity heterogeneities resulted primarily from heterogeneity of Cr(VI) delivery.

  12. Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by 19F- and diffusion-MRI

    PubMed Central

    Bible, Ellen; Dell’Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter; Badylak, Stephen F.; Ahrens, Eric T.; Modo, Michel

    2012-01-01

    Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based 1H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a 19F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on 1H-MRI scans. Twenty percent of cells labeled with the 19F-agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T2- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. PMID:22244696

  13. Non-invasive longitudinal imaging of tumor progression using an 111indium labeled CXCR4 peptide antagonist

    PubMed Central

    Buckle, Tessa; van Berg, Nynke S; Kuil, Joeri; Bunschoten, Anton; Oldenburg, Joppe; Borowsky, Alexander D; Wesseling, Jelle; Masada, Ryo; Oishi, Shinya; Fujii, Nobutaka; van Leeuwen, Fijs WB

    2012-01-01

    The chemokine receptor 4 (CXCR4) is a biomarker that is over-expressed in ductal carcinoma in situ (DCIS). Hence, CXCR4-targeted (molecular) imaging approaches may have diagnostic value in such a challenging, premalignant lesion. The indium labeled CXCR4 peptide-antagonist, 111In-DTPA-Ac-TZ14011, was used to visualize CXCR4-expression in a mammary intraepithelial neoplastic outgrowth (MIN-O) mouse tumor model resembling human DCIS. MIN-O lesion development was longitudinally monitored using SPET/CT and tracer uptake was compared to uptake in control lesions. Expression of CXCR4 was validated using immunohistochemistry and flow cytometric analysis. The uptake of 111In-DTPA-Ac-TZ14011 was related to tumor angiogenesis using 111In-cDTPA-[RGDfK]. Twenty-four hours after tracer injection, MIN-O lesions could be discriminated from low CXCR4-expressing control tumors, while the degree of angiogenesis based on the αvβ3 integrin expression in both tumor types was similar. The uptake of 111In-DTPA-Ac-TZ14011 in early MIN-O lesions was significantly lower than in larger intermediate and late-stage lesions, two-and-a-half-times (p=0.03) and seven-times (p=0.002), respectively. Intermediate and late stage lesions show a higher degree of membranous CXCR4-staining at immunohistochemistry and flow cytometric analysis. From this study we can conclude that 111In-DTPA-Ac-TZ14011 can be used to visualize the CXCR4-expression in MIN-O lesions longitudinally. PMID:23133805

  14. Acoustic radiation force impulse-imaging and transient elastography for non-invasive assessment of liver fibrosis and steatosis in NAFLD.

    PubMed

    Friedrich-Rust, Mireen; Romen, Daniela; Vermehren, Johannes; Kriener, Susanne; Sadet, Dilek; Herrmann, Eva; Zeuzem, Stefan; Bojunga, Joerg

    2012-03-01

    Transient elastography (TE) and acoustic radiation force impulse (ARFI)-imaging have shown promising results for the staging of liver fibrosis. The aim of the present study was to compare ARFI of the left and right liver lobe with TE using the standard and obese probes for the diagnosis of liver fibrosis in NAFL/NASH. In addition, liver steatosis is evaluated using the novel controlled attenuation parameter (CAP). Sixty-one patients with NAFLD/NASH were included in the study. All patients received TE with both probes, ARFI of both liver lobes and CAP. The results were compared with liver histology. 57 patients were included in the final analysis. The diagnostic accuracy for TE measurements with the M-and XL-probe and for ARFI of the right and left liver lobe was 0.73, 0.84, 0.71 and 0.60 for the diagnosis of severe fibrosis, and 0.93, 0.93, 0.74 and 0.90 for the diagnosis of cirrhosis, respectively. No significant difference of results was observed between TE and ARFI in the subgroup of patients with reliable TE-measurement when taking into account the best results of both methods. However, while a significant correlation could be found for TE with histological liver fibrosis, the correlation of ARFI with liver fibrosis was not statistically significant. A significant correlation was found for CAP with histological steatosis (r=0.49, p<0.001). No significant difference in diagnostic accuracy for the non-invasive assessment of liver fibrosis was found for transient elastography and ARFI. Nevertheless TE significantly correlated with liver fibrosis while ARFI did not. CAP enables the non-invasive assessment of steatosis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Non-invasive parenchymal, vascular and metabolic high-frequency ultrasound and photoacoustic rat deep brain imaging.

    PubMed

    Giustetto, Pierangela; Filippi, Miriam; Castano, Mauro; Terreno, Enzo

    2015-03-02

    Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive

  16. Non-invasive Parenchymal, Vascular and Metabolic High-frequency Ultrasound and Photoacoustic Rat Deep Brain Imaging

    PubMed Central

    Giustetto, Pierangela; Filippi, Miriam; Castano, Mauro; Terreno, Enzo

    2015-01-01

    Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive

  17. Design and Experimental Evaluation of a Non-Invasive Microwave Head Imaging System for Intracranial Haemorrhage Detection.

    PubMed

    Mobashsher, A T; Bialkowski, K S; Abbosh, A M; Crozier, S

    2016-01-01

    An intracranial haemorrhage is a life threatening medical emergency, yet only a fraction of the patients receive treatment in time, primarily due to the transport delay in accessing diagnostic equipment in hospitals such as Magnetic Resonance Imaging or Computed Tomography. A mono-static microwave head imaging system that can be carried in an ambulance for the detection and localization of intracranial haemorrhage is presented. The system employs a single ultra-wideband antenna as sensing element to transmit signals in low microwave frequencies towards the head and capture backscattered signals. The compact and low-profile antenna provides stable directional radiation patterns over the operating bandwidth in both near and far-fields. Numerical analysis of the head imaging system with a realistic head model in various situations is performed to realize the scattering mechanism of haemorrhage. A modified delay-and-summation back-projection algorithm, which includes effects of surface waves and a distance-dependent effective permittivity model, is proposed for signal and image post-processing. The efficacy of the automated head imaging system is evaluated using a 3D-printed human head phantom with frequency dispersive dielectric properties including emulated haemorrhages with different sizes located at different depths. Scattered signals are acquired with a compact transceiver in a mono-static circular scanning profile. The reconstructed images demonstrate that the system is capable of detecting haemorrhages as small as 1 cm3. While quantitative analyses reveal that the quality of images gradually degrades with the increase of the haemorrhage's depth due to the reduction of signal penetration inside the head; rigorous statistical analysis suggests that substantial improvement in image quality can be obtained by increasing the data samples collected around the head. The proposed head imaging prototype along with the processing algorithm demonstrates its feasibility for

  18. Design and Experimental Evaluation of a Non-Invasive Microwave Head Imaging System for Intracranial Haemorrhage Detection

    PubMed Central

    Mobashsher, A. T.; Bialkowski, K. S.; Abbosh, A. M.; Crozier, S.

    2016-01-01

    An intracranial haemorrhage is a life threatening medical emergency, yet only a fraction of the patients receive treatment in time, primarily due to the transport delay in accessing diagnostic equipment in hospitals such as Magnetic Resonance Imaging or Computed Tomography. A mono-static microwave head imaging system that can be carried in an ambulance for the detection and localization of intracranial haemorrhage is presented. The system employs a single ultra-wideband antenna as sensing element to transmit signals in low microwave frequencies towards the head and capture backscattered signals. The compact and low-profile antenna provides stable directional radiation patterns over the operating bandwidth in both near and far-fields. Numerical analysis of the head imaging system with a realistic head model in various situations is performed to realize the scattering mechanism of haemorrhage. A modified delay-and-summation back-projection algorithm, which includes effects of surface waves and a distance-dependent effective permittivity model, is proposed for signal and image post-processing. The efficacy of the automated head imaging system is evaluated using a 3D-printed human head phantom with frequency dispersive dielectric properties including emulated haemorrhages with different sizes located at different depths. Scattered signals are acquired with a compact transceiver in a mono-static circular scanning profile. The reconstructed images demonstrate that the system is capable of detecting haemorrhages as small as 1 cm3. While quantitative analyses reveal that the quality of images gradually degrades with the increase of the haemorrhage’s depth due to the reduction of signal penetration inside the head; rigorous statistical analysis suggests that substantial improvement in image quality can be obtained by increasing the data samples collected around the head. The proposed head imaging prototype along with the processing algorithm demonstrates its feasibility

  19. Non-invasive detection of infection in acute pancreatic and acute necrotic collections with diffusion-weighted magnetic resonance imaging: preliminary findings.

    PubMed

    Islim, Filiz; Salik, Aysun Erbahceci; Bayramoglu, Sibel; Guven, Koray; Alis, Halil; Turhan, Ahmet Nuray

    2014-06-01

    The purpose of this study was to evaluate the contribution of diffusion-weighted magnetic resonance imaging (DW-MRI) to the detection of infection in acute pancreatitis-related collections. A total of 21 DW-MRI, and computed tomography (CT) were performed on 20 patients diagnosed as acute pancreatitis with acute peri-pancreatic fluid or necrotic collections. Collections were classified as infected or sterile according to the culture and follow-up results. Collections with gas bubbles on CT images were considered to be infected. Collections with peripheral bright signals on DW-MRI images were considered to be positive, whereas those without signals were considered to be negative. Apparent diffusion coefficient (ADC) values of the peripheral and central parts of the collections were measured. Student's t test was used to compare the means of ADC values of independent groups. Apart from one false positive result, the presence of infection was detected by DW-MRI with 95.2% accuracy. The sensitivity and accuracy of DW-MRI were higher than CT for the detection of infection. The ADC values in the central parts of the collections were significantly different between the infected and sterile groups. DW-MRI can be used as a non-invasive technique for the detection of infection in acute pancreatitis-associated collections.

  20. Non-invasive identification of traditional red lake pigments in fourteenth to sixteenth centuries paintings through the use of hyperspectral imaging technique

    NASA Astrophysics Data System (ADS)

    Vitorino, T.; Casini, A.; Cucci, C.; Melo, M. J.; Picollo, M.; Stefani, L.

    2015-11-01

    The present paper, which focuses on the identification of red lake pigments, in particular madder, brazilwood, and cochineal, addresses the advantages and drawbacks of using reflectance hyperspectral imaging in the visible and near-infrared ranges as a non-invasive method of discrimination between different red organic pigments in cultural heritage objects. Based on reconstructions of paints used in the period extending from the fourteenth to the sixteenth century, prepared with as far as possible historical accuracy, the analyses by means of visible/near-infrared reflectance hyperspectral imaging were carried out with the objective of understanding the most significant differences between these vegetal- and animal-based red lake pigments. The paper discusses the results that were obtained on four original Italian and North European paintings and compared with those from the paint reconstructions, in order to demonstrate how the hyperspectral imaging technique can be usefully and effectively applied to the identification and mapping of red lake pigments in painted surfaces of interest in the conservation field.

  1. Retooling Laser Speckle Contrast Analysis Algorithm to Enhance Non-Invasive High Resolution Laser Speckle Functional Imaging of Cutaneous Microcirculation

    PubMed Central

    Gnyawali, Surya C.; Blum, Kevin; Pal, Durba; Ghatak, Subhadip; Khanna, Savita; Roy, Sashwati; Sen, Chandan K.

    2017-01-01

    Cutaneous microvasculopathy complicates wound healing. Functional assessment of gated individual dermal microvessels is therefore of outstanding interest. Functional performance of laser speckle contrast imaging (LSCI) systems is compromised by motion artefacts. To address such weakness, post-processing of stacked images is reported. We report the first post-processing of binary raw data from a high-resolution LSCI camera. Sharp images of low-flowing microvessels were enabled by introducing inverse variance in conjunction with speckle contrast in Matlab-based program code. Extended moving window averaging enhanced signal-to-noise ratio. Functional quantitative study of blood flow kinetics was performed on single gated microvessels using a free hand tool. Based on detection of flow in low-flow microvessels, a new sharp contrast image was derived. Thus, this work presents the first distinct image with quantitative microperfusion data from gated human foot microvasculature. This versatile platform is applicable to study a wide range of tissue systems including fine vascular network in murine brain without craniotomy as well as that in the murine dorsal skin. Importantly, the algorithm reported herein is hardware agnostic and is capable of post-processing binary raw data from any camera source to improve the sensitivity of functional flow data above and beyond standard limits of the optical system. PMID:28106129

  2. Retooling Laser Speckle Contrast Analysis Algorithm to Enhance Non-Invasive High Resolution Laser Speckle Functional Imaging of Cutaneous Microcirculation

    NASA Astrophysics Data System (ADS)

    Gnyawali, Surya C.; Blum, Kevin; Pal, Durba; Ghatak, Subhadip; Khanna, Savita; Roy, Sashwati; Sen, Chandan K.

    2017-01-01

    Cutaneous microvasculopathy complicates wound healing. Functional assessment of gated individual dermal microvessels is therefore of outstanding interest. Functional performance of laser speckle contrast imaging (LSCI) systems is compromised by motion artefacts. To address such weakness, post-processing of stacked images is reported. We report the first post-processing of binary raw data from a high-resolution LSCI camera. Sharp images of low-flowing microvessels were enabled by introducing inverse variance in conjunction with speckle contrast in Matlab-based program code. Extended moving window averaging enhanced signal-to-noise ratio. Functional quantitative study of blood flow kinetics was performed on single gated microvessels using a free hand tool. Based on detection of flow in low-flow microvessels, a new sharp contrast image was derived. Thus, this work presents the first distinct image with quantitative microperfusion data from gated human foot microvasculature. This versatile platform is applicable to study a wide range of tissue systems including fine vascular network in murine brain without craniotomy as well as that in the murine dorsal skin. Importantly, the algorithm reported herein is hardware agnostic and is capable of post-processing binary raw data from any camera source to improve the sensitivity of functional flow data above and beyond standard limits of the optical system.

  3. Non-invasive imaging in coronary artery disease including anatomical and functional evaluation of ischaemia and viability assessment

    PubMed Central

    Pakkal, M; Raj, V; Mccann, G P

    2011-01-01

    Coronary artery disease has an important impact on the morbidity and mortality statistics and health economics worldwide. Diagnosis of coronary artery disease is important in risk stratification and guides further management. Invasive coronary angiography is the traditional method of imaging the coronary arteries and remains the gold standard. It detects luminal stenosis but provides little information about the vessel wall or plaques. Besides, not all anatomical lesions are functionally significant. This has lent itself to a wide variety of imaging techniques to identify and assess a flow-limiting stenosis. The approach to diagnosis of coronary artery disease is broadly based on anatomical and functional imaging. Coronary CT and MRI of coronary arteries provide an anatomical assessment of coronary stenosis. Coronary calcium score and coronary CT assess subclinical atherosclerosis by assessing the atherosclerotic plaque burden. The haemodynamic significance of a coronary artery stenosis can be assessed by stress radioisotope studies, stress echocardiography and stress MRI. The more recent literature also focuses on plaque assessment and identification of plaques that are likely to give rise to an acute coronary syndrome. There is an explosion of literature on the merits and limitations of the different imaging modalities. This review article will provide an overview of all the imaging modalities in the diagnosis of coronary artery disease. PMID:22723535

  4. Superparamagnetic Iron Oxide Nanoparticles Function as a Long-Term, Multi-Modal Imaging Label for Non-Invasive Tracking of Implanted Progenitor Cells

    PubMed Central

    Pacak, Christina A.; Hammer, Peter E.; MacKay, Allison A.; Dowd, Rory P.; Wang, Kai-Roy; Masuzawa, Akihiro; Sill, Bjoern; McCully, James D.; Cowan, Douglas B.

    2014-01-01

    The purpose of this study was to determine the ability of superparamagnetic iron oxide (SPIO) nanoparticles to function as a long-term tracking label for multi-modal imaging of implanted engineered tissues containing muscle-derived progenitor cells using magnetic resonance imaging (MRI) and X-ray micro-computed tomography (μCT). SPIO-labeled primary myoblasts were embedded in fibrin sealant and imaged to obtain intensity data by MRI or radio-opacity information by μCT. Each imaging modality displayed a detection gradient that matched increasing SPIO concentrations. Labeled cells were then incorporated in fibrin sealant, injected into the atrioventricular groove of rat hearts, and imaged in vivo and ex vivo for up to 1 year. Transplanted cells were identified in intact animals and isolated hearts using both imaging modalities. MRI was better able to detect minuscule amounts of SPIO nanoparticles, while μCT more precisely identified the location of heavily-labeled cells. Histological analyses confirmed that iron oxide particles were confined to viable, skeletal muscle-derived cells in the implant at the expected location based on MRI and μCT. These analyses showed no evidence of phagocytosis of labeled cells by macrophages or release of nanoparticles from transplanted cells. In conclusion, we established that SPIO nanoparticles function as a sensitive and specific long-term label for MRI and μCT, respectively. Our findings will enable investigators interested in regenerative therapies to non-invasively and serially acquire complementary, high-resolution images of transplanted cells for one year using a single label. PMID:25250622

  5. Superparamagnetic iron oxide nanoparticles function as a long-term, multi-modal imaging label for non-invasive tracking of implanted progenitor cells.

    PubMed

    Pacak, Christina A; Hammer, Peter E; MacKay, Allison A; Dowd, Rory P; Wang, Kai-Roy; Masuzawa, Akihiro; Sill, Bjoern; McCully, James D; Cowan, Douglas B

    2014-01-01

    The purpose of this study was to determine the ability of superparamagnetic iron oxide (SPIO) nanoparticles to function as a long-term tracking label for multi-modal imaging of implanted engineered tissues containing muscle-derived progenitor cells using magnetic resonance imaging (MRI) and X-ray micro-computed tomography (μCT). SPIO-labeled primary myoblasts were embedded in fibrin sealant and imaged to obtain intensity data by MRI or radio-opacity information by μCT. Each imaging modality displayed a detection gradient that matched increasing SPIO concentrations. Labeled cells were then incorporated in fibrin sealant, injected into the atrioventricular groove of rat hearts, and imaged in vivo and ex vivo for up to 1 year. Transplanted cells were identified in intact animals and isolated hearts using both imaging modalities. MRI was better able to detect minuscule amounts of SPIO nanoparticles, while μCT more precisely identified the location of heavily-labeled cells. Histological analyses confirmed that iron oxide particles were confined to viable, skeletal muscle-derived cells in the implant at the expected location based on MRI and μCT. These analyses showed no evidence of phagocytosis of labeled cells by macrophages or release of nanoparticles from transplanted cells. In conclusion, we established that SPIO nanoparticles function as a sensitive and specific long-term label for MRI and μCT, respectively. Our findings will enable investigators interested in regenerative therapies to non-invasively and serially acquire complementary, high-resolution images of transplanted cells for one year using a single label.

  6. [Non-invasive ventilation].

    PubMed

    Gallardo Romero, Jose Manuel; García, Teresa Gómez; Sancho Chust, José Norberto; González Martínez, Mónica

    2010-10-01

    The advent of non-invasive mechanical ventilation (NIMV) has radically changed the management of acute and chronic respiratory failure. Over the last few years, the number of possible applications of NIMV has progressively increased, both in the hospital and extrahospital setting. NIMV is now used in all hospitals and resident physicians currently receive specific training -nonexistent until a few years ago- in this modality. It falls to all of us to push forward the clinical and scientific advances represented by the development of NIMV, by promoting the events that accompany better knowledge of the physiopathological bases of ventilation and of its continuous applications in daily clinical practice and by perfecting the elements required for the correct application of this technique. The present review aims to provide a broad overview of NIMV, from the most theoretical knowledge (the physiopathology of NIMV) to the most practical skills (recognition of patient-ventilator asynchrony). Through this progression from the complex to the most basic, or from the basics to the most complex, depending on the perspective taken, we aim to provide deeper knowledge of the concepts required to understand the technical functioning of the ventilator, describing its distinct modes and parameters and the abilities that must be developed for the correct indication, use and monitoring of the technique. We provide a final reflection on other forms of respiratory support that can be offered to patients with ventilatory failure. Copyright © 2010 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.

  7. History of Mexican Easel Paintings from an Altarpiece Revealed by Non-invasive Terahertz Time-Domain Imaging

    NASA Astrophysics Data System (ADS)

    Gomez-Sepulveda, A. M.; Hernandez-Serrano, A. I.; Radpour, R.; Koch-Dandolo, C. L.; Rojas-Landeros, S. C.; Ascencio-Rojas, L. F.; Zarate, Alvaro; Hernandez, Gerardo; Gonzalez-Tirado, R. C.; Insaurralde-Caballero, M.; Castro-Camus, E.

    2017-04-01

    Four easel paintings attributed to Hermenegildo Bustos ( Purísima del Rincón, Guanajuato, Mexico), one of the most renowned painters of the late nineteenth and early twentieth century Mexican art, have been investigated by means of terahertz time-domain imaging (THz-TDI) and standard imaging techniques, such as near-IR reflectography and X-ray radiography. The archival sources and the recent studies on the paintings suggest that the artworks were created in the eighteenth century and underwent several modifications since then until the intervention of Bustos who authored the currently visible depictions. By combining the records of the paintings obtained by imaging with the different methodologies, aspects of the previous depictions and further details on the paintings' history have been revealed, with THz-TDI playing a key role in attributing a chronological evolution of the images. The paintings of Purísima are the first THz-TDI-scanned paintings belonging to the Mexican cultural heritage.

  8. Non-invasive magnetic resonance imaging diagnosis of presumed intermedioradial carpal bone avascular necrosis in the dog

    PubMed Central

    Pownder, Sarah L.; Cooley, Stacy; Hayashi, Kei; Bezuidenhout, Abraham; Koff, Matthew F.; Potter, Hollis G.

    2016-01-01

    A 5-year-old, spayed female Weimaraner dog was evaluated for progressive left forelimb lameness localized to the carpus. Magnetic resonance imaging (MRI) was used to arrive at a presumptive diagnosis of intermedioradial carpal (IRC) bone fracture with avascular necrosis (AVN). To the authors’ knowledge, this is the first report of naturally occurring AVN of the canine IRC diagnosed using MRI. PMID:27493290

  9. History of Mexican Easel Paintings from an Altarpiece Revealed by Non-invasive Terahertz Time-Domain Imaging

    NASA Astrophysics Data System (ADS)

    Gomez-Sepulveda, A. M.; Hernandez-Serrano, A. I.; Radpour, R.; Koch-Dandolo, C. L.; Rojas-Landeros, S. C.; Ascencio-Rojas, L. F.; Zarate, Alvaro; Hernandez, Gerardo; Gonzalez-Tirado, R. C.; Insaurralde-Caballero, M.; Castro-Camus, E.

    2016-12-01

    Four easel paintings attributed to Hermenegildo Bustos (Purísima del Rincón, Guanajuato, Mexico), one of the most renowned painters of the late nineteenth and early twentieth century Mexican art, have been investigated by means of terahertz time-domain imaging (THz-TDI) and standard imaging techniques, such as near-IR reflectography and X-ray radiography. The archival sources and the recent studies on the paintings suggest that the artworks were created in the eighteenth century and underwent several modifications since then until the intervention of Bustos who authored the currently visible depictions. By combining the records of the paintings obtained by imaging with the different methodologies, aspects of the previous depictions and further details on the paintings' history have been revealed, with THz-TDI playing a key role in attributing a chronological evolution of the images. The paintings of Purísima are the first THz-TDI-scanned paintings belonging to the Mexican cultural heritage.

  10. Nonlinear spectroscopy in the near-field: time resolved spectroscopy and subwavelength resolution non-invasive imaging

    NASA Astrophysics Data System (ADS)

    Namboodiri, Mahesh; Khan, Tahirzeb; Karki, Khadga; Kazemi, Mehdi Mohammad; Bom, Sidhant; Flachenecker, Günter; Namboodiri, Vinu; Materny, Arnulf

    2014-04-01

    The combination of near-field microscopy along with nonlinear optical spectroscopic techniques is presented here. The scanning near-field imaging technique can be integrated with nonlinear spectroscopic techniques to improve spatial and axial resolution of the images. Additionally, ultrafast dynamics can be probed down to nano-scale dimension. The review shows some examples for this combination, which resulted in an exciton map and vibrational contrast images with sub-wavelength resolution. Results of two-color femtosecond time-resolved pump-probe experiments using scanning near-field optical microscopy (SNOM) on thin films of the organic semiconductor 3,4,9,10 Perylenetetracarboxylic dianhydride (PTCDA) are presented. While nonlinear Raman techniques have been used to obtain highly resolved images in combination with near-field microscopy, the use of femtosecond laser pulses in electronic resonance still constitutes a big challenge. Here, we present our first results on coherent anti-Stokes Raman scattering (fs-CARS) with femtosecond laser pulses detected in the near-field using SNOM. We demonstrate that highly spatially resolved images can be obtained from poly(3-hexylthiophene) (P3HT) nano-structures where the fs-CARS process was in resonance with the P3HT absorption and with characteristic P3HT vibrational modes without destruction of the samples. Sub-diffraction limited lateral resolution is achieved. Especially the height resolution clearly surpasses that obtained with standard microCARS. These results will be the basis for future investigations of mode-selective dynamics in the near-field.

  11. Molecular imaging in atherosclerosis.

    PubMed

    Glaudemans, Andor W J M; Slart, Riemer H J A; Bozzao, Alessandro; Bonanno, Elena; Arca, Marcello; Dierckx, Rudi A J O; Signore, Alberto

    2010-12-01

    Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat

  12. Melanomas non-invasive diagnosis application based on the ABCD rule and pattern recognition image processing algorithms.

    PubMed

    Isasi, A Gola; Zapirain, B García; Zorrilla, A Méndez

    2011-09-01

    In this paper an automated dermatological tool for the parameterization of melanomas is presented. The system is based on the standard ABCD Rule and dermatological Pattern Recognition protocols. On the one hand, a complete stack of algorithms for the asymmetry, border, color, and diameter parameterization were developed. On the other hand, three automatic algorithms for digital image processing have been developed in order to detect the appropriate patterns. These allow one to calculate certain quantitative features based on the aspect and inner patterns of the melanoma using simple-operation algorithms, in order to minimize response time. The database used consists of 160 500 x 500-pixel RGB images (20 images per pattern) cataloged by dermatologists, and the results have turned out to be successful according to assessment by medical experts. While the ABCD algorithms are mathematically reliable, the proposed algorithms for pattern recognition produced a remarkable rate of globular, reticular, and blue veil Pattern recognition, with an average above 85% of accuracy. It thus proves to be a reliable system when performing a diagnosis.

  13. Combination of optoacoustics and ultrasound imaging for non-invasive, rapid assessment, and management of circulatory shock

    NASA Astrophysics Data System (ADS)

    Petrov, Yuriy; Petrov, Irene Y.; Esenaliev, Rinat O.; Kinsky, Michael; Prough, Donald S.

    2011-03-01

    We developed a noninvasive, optoacoustic diagnostic platform for monitoring of multiple physiologic variables in inpatients and outpatients. One of the most important applications of this platform is noninvasive, rapid assessment and management of circulatory shock, a common condition in critically ill patients. At present, monitoring of circulatory shock requires measurement of central venous blood oxygenation using invasive procedures such as insertion of catheters in central veins. Hemoglobin saturation below 70% in central veins indicates circulatory shock that requires immediate treatment. We built a portable optoacoustic system for noninvasive measurement of central venous oxygenation. In this study we used the optoacoustic system and clinical ultrasound imaging systems for rapid optoacoustic probing of these veins. The optoacoustic system utilizes a custom-made, sensitive optoacoustic probe that was developed in our laboratory for monitoring of blood oxygenation in deep blood vessels. The studies were performed in human subjects with different geometry (depth, size) of the veins. The ultrasound imaging systems permitted rapid identification of specific blood vessels for optoacoustic probing. We developed a novel algorithm for continuous, realtime, and precise measurement of blood oxygenation in blood vessels. Precision of central venous oxygenation measurement obtained in the study was very high: 1%. Our results indicate that the combination of optoacoustics and ultrasound imaging systems can provide more rapid and accurate assessment and management of the circulatory shock.

  14. EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as non-invasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate

    PubMed Central

    Matsumoto, Shingo; Saito, Keita; Yasui, Hironobu; Morris, H. Douglas; Munasinghe, Jeeva P.; Lizak, Martin; Merkle, Hellmut; Ardenkjaer-Larsen, Jan Henrik; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Koretsky, Alan P.; Mitchell, James B.; Krishna, Murali C.

    2012-01-01

    The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation, and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate (3-BP) blocks glycolysis pathway by inhibiting hypoxia inducible enzymes, and enhanced cytotoxicity of 3-BP under hypoxic conditions has been reported in vitro. However, the efficacy of 3-BP was substantially attenuated in hypoxic tumor regions (pO2 < 10 mmHg) in vivo using squamous cell carcinoma (SCCVII)-bearing mouse model. Metabolic MRI studies using hyperpolarized 13C-labeled pyruvate showed that monocarboxylate transporter-1 (MCT1) is the major transporter for pyruvate and the analog 3-BP in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of MCT1 in vivo. Expression of MCT1 was enhanced in moderately hypoxic (8–15 mmHg) tumor regions, but down regulated in severely hypoxic (< 5 mmHg) tumor regions. These results emphasize the importance of non-invasive imaging biomarkers to confirm the action of hypoxia-activated drugs. PMID:22692861

  15. Diffusion-weighted imaging for non-invasive and quantitative monitoring of bone marrow infiltration in patients with monoclonal plasma cell disease: a comparative study with histology.

    PubMed

    Hillengass, Jens; Bäuerle, Tobias; Bartl, Reiner; Andrulis, Mindaugas; McClanahan, Fabienne; Laun, Frederik B; Zechmann, Christian Martin; Shah, Rajiv; Wagner-Gund, Barbara; Simon, Dirk; Heiss, Christiane; Neben, Kai; Ho, Anthony D; Schlemmer, Heinz-Peter; Goldschmidt, Hartmut; Delorme, Stefan; Stieltjes, Bram

    2011-06-01

    Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow biopsy or aspiration. Diffusion-weighted imaging (DWI) is a magnetic resonance imaging-technique that may mirror tissue cellularity by measuring random movements of water molecules. To investigate if DWI is capable of assessing bone marrow cellularity in monoclonal plasma cell disease, we investigated 56 patients with multiple myeloma or monoclonal gammopathy of undetermined significance, and 30 healthy controls using DWI of the pelvis and/or the lumbar spine. In 25 of 30 patients who underwent biopsy, bone marrow trephine and DWI could be compared. Of the patients with symptomatic disease 15 could be evaluated after systemic treatment. There was a positive correlation between the DWI-parameter apparent diffusion coefficient (ADC) and bone marrow cellularity as well as micro-vessel density (P<0·001 respectively). ADC was significantly different between patients and controls (P<0·01) and before and after systemic therapy (P<0·001). In conclusion, DWI enabled bone marrow infiltration to be monitored in a non-invasive, quantitative way, suggesting that after further investigations on larger patient groups this might become an useful tool in the clinical work-up to assess tumour burden. © 2011 Blackwell Publishing Ltd.

  16. Non invasive imaging assessment of the biodistribution of GSK2849330, an ADCC and CDC optimized anti HER3 mAb, and its role in tumor macrophage recruitment in human tumor-bearing mice.

    PubMed

    Alsaid, Hasan; Skedzielewski, Tinamarie; Rambo, Mary V; Hunsinger, Kristen; Hoang, Bao; Fieles, William; Long, Edward R; Tunstead, James; Vugts, Danielle J; Cleveland, Matthew; Clarke, Neil; Matheny, Christopher; Jucker, Beat M

    2017-01-01

    The purpose of this work was to use various molecular imaging techniques to non-invasively assess GSK2849330 (anti HER3 ADCC and CDC enhanced 'AccretaMab' monoclonal antibody) pharmacokinetics and pharmacodynamics in human xenograft tumor-bearing mice. Immuno-PET biodistribution imaging of radiolabeled 89Zr-GSK2849330 was assessed in mice with HER3 negative (MIA-PaCa-2) and positive (CHL-1) human xenograft tumors. Dose dependency of GSK2849330 disposition was assessed using varying doses of unlabeled GSK2849330 co-injected with 89Zr-GSK2849330. In-vivo NIRF optical imaging and ex-vivo confocal microscopy were used to assess the biodistribution of GSK2849330 and the HER3 receptor occupancy in HER3 positive xenograft tumors (BxPC3, and CHL-1). Ferumoxytol (USPIO) contrast-enhanced MRI was used to investigate the effects of GSK2849330 on tumor macrophage content in CHL-1 xenograft bearing mice. Immuno-PET imaging was used to monitor the whole body drug biodistribution and CHL-1 xenograft tumor uptake up to 144 hours post injection of 89Zr-GSK2849330. Both hepatic and tumor uptake were dose dependent and saturable. The optical imaging data in the BxPC3 xenograft tumor confirmed the tumor dose response finding in the Immuno-PET study. Confocal microscopy showed a distinguished cytoplasmic punctate staining pattern within individual CHL-1 cells. GSK2849330 inhibited tumor growth and this was associated with a significant decrease in MRI signal to noise ratio after USPIO injection and with a significant increase in tumor macrophages as confirmed by a quantitative immunohistochemistry analysis. By providing both dose response and time course data from both 89Zr and fluorescently labeled GSK2849330, complementary imaging studies were used to characterize GSK2849330 biodistribution and tumor uptake in vivo. Ferumoxytol-enhanced MRI was used to monitor aspects of the immune system response to GSK2849330. Together these approaches potentially provide clinically translatable

  17. Quantitative phase imaging of cellular and subcellular structures for non-invasive screening diagnostics of socially significant diseases

    NASA Astrophysics Data System (ADS)

    Vasilenko, Irina; Metelin, Vladislav; Nasyrov, Marat; Belyakov, Vladimir; Kuznetsov, Alexander; Sukhenko, Evgeniy

    2015-03-01

    The objective of the present study is to increase the quality of the early diagnosis using cytological differential-diagnostic criteria for reactive changes in the nuclear structures of the immunocompetent cells. The morphofunctional status of living cells were estimated in the real time using new technologic platform of the hardware-software complex for phase cell imaging. The level of functional activity for lymphocyte subpopulations was determined on the base of modification of nuclear structures and decreasing of nuclear phase thickness. The dynamics of nuclear parameters was used as the quantitative measuring for cell activating level and increasing of proliferative potential.

  18. Non-invasive imaging of cardiac transgene expression with PET: comparison of the human sodium/iodide symporter gene and HSV1-tk as the reporter gene.

    PubMed

    Miyagawa, Masao; Anton, Martina; Wagner, Bettina; Haubner, Roland; Souvatzoglou, Michael; Gansbacher, Bernd; Schwaiger, Markus; Bengel, Frank M

    2005-09-01

    Genes encoding for intracellular enzymes or transmembrane proteins are suitable as reporters, but may differ in terms of applicability for cardiac imaging. The aim of this study was to compare the human sodium iodide symporter gene (hNIS) with the herpes simplex virus type 1 thymidine kinase gene (HSV1-tk) as the reporter gene in non-invasive imaging of cardiac transgene expression with positron emission tomography (PET). Equal doses of adenoviral vectors encoding for hNIS, wild-type HSV1-tk, mutant HSV1-sr39tk or LacZ as the control gene were directly injected into the myocardium of 34 animals. Two days later, dynamic PET was performed with a clinical scanner, using reporter probes specific for the respective reporter gene. Imaging with (13)N-ammonia was also performed to identify cardiac regions of interest. Kinetics differed significantly: (124)I as the probe for hNIS showed rapid early uptake, remaining stable over time. Maximal myocardial concentration was 3.61+/-1.15%. The nucleoside (18)F-FHBG, as the specific probe for HSV1-sr39tk, showed increasing uptake over time, but maximal accumulation was significantly lower (1.45+/-0.54%, P=0.0009). (124)I-FIAU, as the specific probe for wild-type HSV1-tk, showed early uptake with subsequent washout. Maximal accumulation was lowest (0.63+/-0.23%, P<0.0001). Post-mortem analysis by autoradiography and gamma counting confirmed the in vivo data. Reporter genes encoding for transporter proteins such as hNIS are an attractive alternative to overexpression of intracellular enzymes for cardiac gene product imaging. hNIS yielded higher signal intensity and imaging contrast for PET than did HSV1-tk and HSV1-sr39tk. Therefore, this approach may be preferable for the future monitoring of cardiac gene- or cell-based therapy.

  19. Non-invasive neurochemical analysis of focal excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging.

    PubMed

    Jenkins, B G; Brouillet, E; Chen, Y C; Storey, E; Schulz, J B; Kirschner, P; Beal, M F; Rosen, B R

    1996-05-01

    Water-suppressed chemical shift magnetic resonance imaging was used to detect neurochemical alterations in vivo in neurotoxin-induced rat models of Huntington's and Parkinson's disease. The toxins were: N-methyl-4-phenylpyridinium (MPP+), aminooxyacetic acid (AOAA), 3-nitropropionic acid (3-NP), malonate, and azide. Local or systemic injection of these compounds caused secondary excitotoxic lesions by selective inhibition of mitochondrial respiration that gave rise to elevated lactate concentrations in the striatum. In addition, decreased N-acetylaspartate (NAA) concentrations were noted at the lesion site over time. Measurements of lactate washout kinetics demonstrated that t1/2 followed the order: 3-NP approximately MPP+ > AOAA approximately malonate, which parallels the expected lifetimes of the neurotoxins based on their mechanisms of action. Further increases in lactate were also caused by intravenous infusion of glucose. At least part of the excitotoxicity is mediated through indirect glutamate pathways because lactate production and lesion size were diminished using unilateral decortectomies (blockade of glutamatergic input) or glutamate antagonists (MK-801). Lesion size and lactate were also diminished by energy repletion with ubiquinone and nicotinamide. Lactate measurements determined by magnetic resonance agreed with biochemical measurements made using freeze clamp techniques. Lesion size as measured with MR, although larger by 30%, agreed well with lesion size determined histologically. These experiments provide evidence for impairment of intracellular energy metabolism leading to indirect excitotoxicity for all the compounds mentioned before and demonstrate the feasibility of small-volume metabolite imaging for in vivo neurochemical analysis.

  20. Non-invasive depth profile imaging of the stratum corneum using confocal Raman microscopy: first insights into the method.

    PubMed

    Ashtikar, Mukul; Matthäus, Christian; Schmitt, Michael; Krafft, Christoph; Fahr, Alfred; Popp, Jürgen

    2013-12-18

    The stratum corneum is a strong barrier that must be overcome to achieve successful transdermal delivery of a pharmaceutical agent. Many strategies have been developed to enhance the permeation through this barrier. Traditionally, drug penetration through the stratum corneum is evaluated by employing tape-stripping protocols and measuring the content of the analyte. Although effective, this method cannot provide a detailed information regarding the penetration pathways. To address this issue various microscopic techniques have been employed. Raman microscopy offers the advantage of label free imaging and provides spectral information regarding the chemical integrity of the drug as well as the tissue. In this paper we present a relatively simple method to obtain XZ-Raman profiles of human stratum corneum using confocal Raman microscopy on intact full thickness skin biopsies. The spectral datasets were analysed using a spectral unmixing algorithm. The spectral information obtained, highlights the different components of the tissue and the presence of drug. We present Raman images of untreated skin and diffusion patterns for deuterated water and beta-carotene after Franz-cell diffusion experiment. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with {sup 18}F-Al labeled Cys{sup 39}-exendin-4

    SciTech Connect

    Mi, Baoming; Xu, Yuping; Pan, Donghui; Wang, Lizhen; Yang, Runlin; Yu, Chunjing; Wan, Weixing; Wu, Yiwei; Yang, Min

    2016-02-26

    Purpose: Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, {sup 18}F-Al labeled exendin-4 analog, {sup 18}F-Al-NOTA-MAL-Cys{sup 39}-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. Methods: The targeting of {sup 18}F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with {sup 18}F-Al-NOTA-MAL-Cys{sup 39}-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. Results: The pancreas of healthy rats was readily visualized after administration of {sup 18}F-Al-NOTA-MAL-Cys{sup 39}-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. Conclusion: The favorable preclinical data indicated that {sup 18}F-Al-NOTA-MAL-Cys{sup 39}-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells.

  2. Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with (18)F-Al labeled Cys(39)-exendin-4.

    PubMed

    Mi, Baoming; Xu, Yuping; Pan, Donghui; Wang, Lizhen; Yang, Runlin; Yu, Chunjing; Wan, Weixing; Wu, Yiwei; Yang, Min

    2016-02-26

    Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, (18)F-Al labeled exendin-4 analog, (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. The targeting of (18)F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with (18)F-Al-NOTA-MAL-Cys(39)-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. The pancreas of healthy rats was readily visualized after administration of (18)F-Al-NOTA-MAL-Cys(39)-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. The favorable preclinical data indicated that (18)F-Al-NOTA-MAL-Cys(39)-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Non-invasive, whole-plant imaging of chloroplast movement and chlorophyll fluorescence reveals photosynthetic phenotypes independent of chloroplast photorelocation defects in chloroplast division mutants.

    PubMed

    Dutta, Siddhartha; Cruz, Jeffrey A; Jiao, Yuhua; Chen, Jin; Kramer, David M; Osteryoung, Katherine W

    2015-10-01

    Leaf chloroplast movement is thought to optimize light capture and to minimize photodamage. To better understand the impact of chloroplast movement on photosynthesis, we developed a technique based on the imaging of reflectance from leaf surfaces that enables continuous, high-sensitivity, non-invasive measurements of chloroplast movement in multiple intact plants under white actinic light. We validated the method by measuring photorelocation responses in Arabidopsis chloroplast division mutants with drastically enlarged chloroplasts, and in phototropin mutants with impaired photorelocation but normal chloroplast morphology, under different light regimes. Additionally, we expanded our platform to permit simultaneous image-based measurements of chlorophyll fluorescence and chloroplast movement. We show that chloroplast division mutants with enlarged, less-mobile chloroplasts exhibit greater photosystem II photodamage than is observed in the wild type, particularly under fluctuating high levels of light. Comparison between division mutants and the severe photorelocation mutant phot1-5 phot2-1 showed that these effects are not entirely attributable to diminished photorelocation responses, as previously hypothesized, implying that altered chloroplast morphology affects other photosynthetic processes. Our dual-imaging platform also allowed us to develop a straightforward approach to correct non-photochemical quenching (NPQ) calculations for interference from chloroplast movement. This correction method should be generally useful when fluorescence and reflectance are measured in the same experiments. The corrected data indicate that the energy-dependent (qE) and photoinhibitory (qI) components of NPQ contribute differentially to the NPQ phenotypes of the chloroplast division and photorelocation mutants. This imaging technology thus provides a platform for analyzing the contributions of chloroplast movement, chloroplast morphology and other phenotypic attributes to the

  4. Identifying Model Inaccuracies and Solution Uncertainties in Non-Invasive Activation-Based Imaging of Cardiac Excitation using Convex Relaxation

    PubMed Central

    Erem, Burak; van Dam, Peter M.; Brooks, Dana H.

    2014-01-01

    Noninvasive imaging of cardiac electrical function has begun to move towards clinical adoption. Here we consider one common formulation of the problem, in which the goal is to estimate the spatial distribution of electrical activation times during a cardiac cycle. We address the challenge of understanding the robustness and uncertainty of solutions to this formulation. This formulation poses a non-convex, non-linear least squares optimization problem. We show that it can be relaxed to be convex, at the cost of some degree of physiological realism of the solution set, and that this relaxation can be used as a framework to study model inaccuracy and solution uncertainty. We present two examples, one using data from a healthy human subject and the other synthesized with the ECGSIM software package. In the first case, we consider uncertainty in the initial guess and regularization parameter. In the second case, we mimic the presence of an ischemic zone in the heart in a way which violates a model assumption. We show that the convex relaxation allows understanding of spatial distribution of parameter sensitivity in the first case, and identification of model violation in the second. PMID:24710159

  5. Non Invasive High Resolution In Vivo Imaging of α-napthylisothiocyanate (ANIT) Induced Hepatobiliary Toxicity in STII Medaka

    PubMed Central

    Hardman, Ron; Kullman, Seth; Yuen, Bonny; Hinton, David E.

    2009-01-01

    A novel transparent stock of medaka (Oryzias latipes; STII), homozygous recessive for all four pigments (iridophores, xanthophores, leucophores, melanophores), permits transcutaneous, high resolution ( < 1μm) imaging of internal organs and tissues in living individuals. We applied this model to in vivo investigation of α-napthylisothiocyanate (ANIT) induced hepatobiliary toxicity. Distinct phenotypic responses to ANIT involving all aspects of intrahepatic biliary passageways (IHBPs), particularly bile preductular epithelial cells (BPDECs), associated with transitional passageways between canaliculi and bile ductules, were observed. Alterations included: attenuation/dilation of bile canaliculi, bile preductular lesions, hydropic vacuolation of hepatocytes and BPDECs, mild BPDEC hypertrophy, and biliary epithelial cell (BEC) hyperplasia. Ex vivo histological, immunohistochemical, and ultrastructural studies were employed to aid in interpretation of, and verify, in vivo findings. 3D reconstructions from in vivo investigations provided quantitative morphometric and volumetric evaluation of ANIT exposed and untreated livers. The findings presented show for the first time in vivo evaluation of toxicity in the STII medaka hepatobiliary system, and, in conjunction with prior in vivo work characterizing normalcy, advance our comparative understanding of this lower vertebrate hepatobiliary system and its response to toxic insult. PMID:18022256

  6. A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy

    NASA Astrophysics Data System (ADS)

    Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Wu, Hailiang; Terada, Yasuko; Saga, Tsuneo; Aoki, Ichio; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2016-08-01

    Engineered nanoparticles that respond to pathophysiological parameters, such as pH or redox potential, have been developed as contrast agents for the magnetic resonance imaging (MRI) of tumours. However, beyond anatomic assessment, contrast agents that can sense these pathological parameters and rapidly amplify their magnetic resonance signals are desirable because they could potentially be used to monitor the biological processes of tumours and improve cancer diagnosis. Here, we report an MRI contrast agent that rapidly amplifies magnetic resonance signals in response to pH. We confined Mn2+ within pH-sensitive calcium phosphate (CaP) nanoparticles comprising a poly(ethylene glycol) shell. At a low pH, such as in solid tumours, the CaP disintegrates and releases Mn2+ ions. Binding to proteins increases the relaxivity of Mn2+ and enhances the contrast. We show that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic regions within the tumour mass and detect invisible millimetre-sized metastatic tumours in the liver.

  7. Non-invasive Imaging and Tracking of Engineered Human Muscle Precursor Cells for Skeletal Muscle Tissue Engineering Using Positron Emission Tomography

    PubMed Central

    Haralampieva, Deana; Betzel, Thomas; Dinulovic, Ivana; Salemi, Souzan; Stoelting, Meline; Kraemer, Stefanie; Schibli, Roger; Sulser, Tullio; Handschin, Christoph; Eberli, Daniel; Ametamey, Simon M.

    2016-01-01

    Transplantation of human muscle precursor cells (hMPCs) is envisioned for the treatment of various muscle diseases. However, a feasible non-invasive tool to monitor cell survival, migration and integration into the host tissue is still missing. Methods In this study, we designed an adenoviral delivery system to genetically modify hMPCs to express a signaling-deficient form of a human dopamine D2 receptor (hD2R). The gene expression levels of the receptor were evaluated by Reverse Transcriptase Polymerase Chain Reaction (RTPCR) and infection efficiency was visualized by fluorescent microscopy. Viability, proliferation and differentiation capacity of the transduced cells were confirmed and their sustained myogenic phenotype was shown by flow cytometry analysis and fluorescent microscopy. 18F-Fallypride and 18F-FMISO, two well-established PET radioligands, were successfully synthesized and evaluated for their potential to image engineered hMPCs in a mouse model. Furthermore, biodistribution studies and autoradiography were also performed to determine the extent of signal specificity. Results To address the feasibility of the presented approach for tracking of hMPCs in an in vivo model, we first evaluated the safety of the adenoviral gene-delivery, which showed no detrimental effects on the primary human cells. Specific binding of 18F-Fallypride to hD2R_hMPCs was demonstrated in vitro, as well as in vivo, by performing autoradiography, biodistribution and PET experiments, respectively. Furthermore, 18F-FMISO uptake was evaluated at different time-points after cell inoculation in vivo, showing high signal only at the early stages. Finally, histological assessment of the harvested tissues confirmed the sustained survival of the transplanted cells at different time-points with formation of muscle tissue at the site of injection. Conclusion We here propose a signaling-deficient human D2R as a potent reporter for in vivo hMPCs PET tracking by 18F-Fallypride. This approach

  8. Non-invasive skin oxygenation imaging using a multi-spectral camera system: effectiveness of various concentration algorithms applied on human skin

    NASA Astrophysics Data System (ADS)

    Klaessens, John H. G. M.; Noordmans, Herke Jan; de Roode, Rowland; Verdaasdonk, Rudolf M.

    2009-02-01

    This study describes noninvasive noncontact methods to acquire and analyze functional information from the skin. Multispectral images at several selected wavelengths in the visible and near infrared region are collected and used in mathematical methods to calculate concentrations of different chromophores in the epidermis and dermis of the skin. This is based on the continuous wave Near Infrared Spectroscopy method, which is a well known non-invasive technique for measuring oxygenation changes in the brain and in muscle tissue. Concentration changes of hemoglobin (dO2Hb, dHHb and dtHb) can be calculated from light attenuations using the modified Lambert Beer equation. We applied this technique on multi-spectral images taken from the skin surface using different algorithms for calculating changes in O2Hb, HHb and tHb. In clinical settings, the imaging of local oxygenation variations and/or blood perfusion in the skin can be useful for e.g. detection of skin cancer, detection of early inflammation, checking the level of peripheral nerve block anesthesia, study of wound healing and tissue viability by skin flap transplantations. Images from the skin are obtained with a multi-spectral imaging system consisting of a 12-bit CCD camera in combination with a Liquid Crystal Tunable Filter. The skin is illuminated with either a broad band light source or a tunable multi wavelength LED light source. A polarization filter is used to block the direct reflected light. The collected multi-spectral imaging data are images of the skin surface radiance; each pixel contains either the full spectrum (420 - 730 nm) or a set of selected wavelengths. These images were converted to reflectance spectra. The algorithms were validated during skin oxygen saturation changes induced by temporary arm clamping and applied to some clinical examples. The initial results with the multi-spectral skin imaging system show good results for detecting dynamic changes in oxygen concentration. However, the

  9. Non-invasive evaluation of neuroprotective drug candidates for cerebral infarction by PET imaging of mitochondrial complex-I activity

    NASA Astrophysics Data System (ADS)

    Fukuta, Tatsuya; Asai, Tomohiro; Ishii, Takayuki; Koide, Hiroyuki; Kiyokawa, Chiaki; Hashimoto, Masahiro; Kikuchi, Takashi; Shimizu, Kosuke; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto

    2016-07-01

    The development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) for detecting activity of mitochondrial complex I (MC-I). This probe was shown to visualize neuronal damage in the living brain of rodent and primate models of neurodegenerative diseases. In the present study, [18F]BCPP-EF was applied to evaluate the therapeutic effects of a neuroprotectant, liposomal FK506 (FK506-liposomes), on cerebral ischemia/reperfusion (I/R) injury in transient middle cerebral artery occlusion rats. The PET imaging using [18F]BCPP-EF showed a prominent reduction in the MC-I activity in the ischemic brain hemisphere. Treatment with FK506-liposomes remarkably increased the uptake of [18F]BCPP-EF in the ischemic side corresponding to the improvement of blood flow disorders and motor function deficits throughout the 7 days after I/R. Additionally, the PET scan could diagnose the extent of the brain damage accurately and showed the neuroprotective effect of FK506-liposomes at Day 7, at which 2, 3, 5-triphenyltetrazolium chloride staining couldn’t visualize them. Our study demonstrated that the PET technology using [18F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain.

  10. Non-invasive evaluation of neuroprotective drug candidates for cerebral infarction by PET imaging of mitochondrial complex-I activity

    PubMed Central

    Fukuta, Tatsuya; Asai, Tomohiro; Ishii, Takayuki; Koide, Hiroyuki; Kiyokawa, Chiaki; Hashimoto, Masahiro; Kikuchi, Takashi; Shimizu, Kosuke; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto

    2016-01-01

    The development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) for detecting activity of mitochondrial complex I (MC-I). This probe was shown to visualize neuronal damage in the living brain of rodent and primate models of neurodegenerative diseases. In the present study, [18F]BCPP-EF was applied to evaluate the therapeutic effects of a neuroprotectant, liposomal FK506 (FK506-liposomes), on cerebral ischemia/reperfusion (I/R) injury in transient middle cerebral artery occlusion rats. The PET imaging using [18F]BCPP-EF showed a prominent reduction in the MC-I activity in the ischemic brain hemisphere. Treatment with FK506-liposomes remarkably increased the uptake of [18F]BCPP-EF in the ischemic side corresponding to the improvement of blood flow disorders and motor function deficits throughout the 7 days after I/R. Additionally, the PET scan could diagnose the extent of the brain damage accurately and showed the neuroprotective effect of FK506-liposomes at Day 7, at which 2, 3, 5-triphenyltetrazolium chloride staining couldn’t visualize them. Our study demonstrated that the PET technology using [18F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain. PMID:27440054

  11. Non-invasive assessment of liver fibrosis in a rat model: shear wave elasticity imaging versus real-time elastography.

    PubMed

    Lin, Sen-Hao; Ding, Hong; Mao, Feng; Xue, Li-Yun; Lv, Wei-Wei; Zhu, Hong-Guang; Huang, Bei-Jian; Wang, Wen-Ping

    2013-07-01

    The purpose of this study was to investigate the diagnostic value of shear wave elasticity imaging (SWEI) and real-time elastography (RTE) in liver fibrosis induced by dimethylnitrosamine (DMN) and to compare the accuracy of these methods. Seventy male Wistar rats given a single intra-peritoneal injection of DMN and 10 control rats given a saline injection underwent SWEI and RTE to determine their shear wave velocity (V(s)) and liver fibrosis (LF) index, respectively. Correlations between V(s) or the LF index and histologic stage of liver fibrosis (S0-S4) were analyzed, and the diagnostic values of the techniques were assessed using a receiver operating characteristic curve. A positive correlation was found between V(s) and stage of liver fibrosis (r = 0.947, p < 0.001) and between LF index and stage (S) of liver fibrosis (r = 0.662, p < 0.001). For Vs, the areas under the receiver operating characteristic curve for the diagnosis of fibrosis, S ≥ S1, S ≥ S2, S ≥ S3 and S = S4, were 0.983, 0.995, 0.999 and 0.964, respectively; for the LF index, the values were 0.871, 0.887, 0.761 and 0.839, respectively (all p < 0.001). Vs and the LF index values in rats with severe inflammatory activity were significantly higher than those in controls (p < 0.001). In conclusion, positive correlations exist between V(s) or the LF index and the severity of liver fibrosis in rats. Vs is more accurate than the LF index in predicting liver fibrosis in rats. However, severe inflammatory activity may reduce the accuracy of both techniques.

  12. Non-invasive mapping of bilateral motor speech areas using navigated transcranial magnetic stimulation and functional magnetic resonance imaging.

    PubMed

    Könönen, Mervi; Tamsi, Niko; Säisänen, Laura; Kemppainen, Samuli; Määttä, Sara; Julkunen, Petro; Jutila, Leena; Äikiä, Marja; Kälviäinen, Reetta; Niskanen, Eini; Vanninen, Ritva; Karjalainen, Pasi; Mervaala, Esa

    2015-06-15

    Navigated transcranial magnetic stimulation (nTMS) is a modern precise method to activate and study cortical functions noninvasively. We hypothesized that a combination of nTMS and functional magnetic resonance imaging (fMRI) could clarify the localization of functional areas involved with motor control and production of speech. Navigated repetitive TMS (rTMS) with short bursts was used to map speech areas on both hemispheres by inducing speech disruption during number recitation tasks in healthy volunteers. Two experienced video reviewers, blinded to the stimulated area, graded each trial offline according to possible speech disruption. The locations of speech disrupting nTMS trials were overlaid with fMRI activations of word generation task. Speech disruptions were produced on both hemispheres by nTMS, though there were more disruptive stimulation sites on the left hemisphere. Grade of the disruptions varied from subjective sensation to mild objectively recognizable disruption up to total speech arrest. The distribution of locations in which speech disruptions could be elicited varied among individuals. On the left hemisphere the locations of disturbing rTMS bursts with reviewers' verification followed the areas of fMRI activation. Similar pattern was not observed on the right hemisphere. The reviewer-verified speech disruptions induced by nTMS provided clinically relevant information, and fMRI might explain further the function of the cortical area. nTMS and fMRI complement each other, and their combination should be advocated when assessing individual localization of speech network. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 3D magnetic resonance imaging as a non-invasive tool for investigating water-filled karst formations

    NASA Astrophysics Data System (ADS)

    Legchenko, A.; Ezersky, M.; Boucher, M.; Chevalier, A.; Vouillamoz, J.-M.

    2012-04-01

    Magnetic Resonance Sounding (MRS) is a geophysical technique developed for groundwater exploration. MRS can be used for reliable identification of karst aquifers because of the relaxation time of the magnetic resonance signal (T1) is longer for bulk water in karst caverns and channels (about 2 s) than for water in porous rock (few tens of ms). MRS is sensitive primary to groundwater volume but electrically conductive layers modify electromagnetic fields in the subsurface and thus may have an effect on MRS performance. Generally, the study of a karst requires a 3D field set-up and we developed a measuring procedure and interpretation software that makes it possible to image heterogeneous water-bearing geological formations down to about 80 m (3D-SNMR method). Numerical modeling results show that limited resolution of the method allows only identification of large karst formations. For example detectable karst should be larger than a few hundred cubic meters when karst is located close to the surface and a few thousand cubic meters when it is located at 60 m. Time Domain Electromagnetic method (TDEM) is known as an efficient tool for investigating electrical conductivity of rocks. TDEM results allow more accurate computing of the EM field in the subsurface and thus contribute for improving accuracy of MRS results. TDEM and 3D-SNMR methods were applied jointly in the Dead Sea coast of Israel (Nahal Hever South). The subsurface in this area is heterogeneous and composed of intercalated sand and clay layers over a salt rock, which is partly karstified. Groundwater is very saline, with a chloride concentration of 100-225 g/l thus rendering the resistivity of geological formations less than 1 ohm-m. We have shown numerically that under Dead Sea coast conditions, 3D-SNMR is able to detect and to locate the target within an error of a few tens of meters. In the investigated area (500×500 m2) our results reveal a very heterogeneous shallow aquifer that could be divided into

  14. The Assessment of Inter-Hemispheric Imbalance using Imaging and Non-Invasive Brain Stimulation in Patients with Chronic Stroke

    PubMed Central

    Cunningham, David A.; Machado, Andre; Janini, Daniel; Varnerin, Nicole; Bonnett, Corin; Yue, Guang; Jones, Stephen; Lowe, Mark; Beall, Erik; Sakaie, Ken; Plow, Ela B.

    2014-01-01

    OBJECTIVE To determine how inter-hemispheric balance in stroke, measured using transcranial magnetic stimulation (TMS), relates to balance defined using neuroimaging (functional magnetic resonance (fMRI) and diffusion tensor imaging (DTI)), and how these metrics of balance are associated with clinical measures of upper limb function and disability. DESIGN Cross-Sectional SETTING Clinical Research Laboratory PARTICIPANTS Ten chronic stroke patients (63±9 years) in a population based sample with unilateral upper-limb paresis. INTERVENTION Not applicable MAIN OUTCOME MEASURES Inter-hemispheric balance was measured with TMS, fMRI and DTI. TMS defined inter-hemispheric differences in recruitment of corticospinal output, the size of the corticomotor output maps and the degree of mutual transcallosal inhibition they exerted upon one another. fMRI studied whether cortical activation during the movement of the paretic hand was lateralized to the ipsilesional or to the contralesional primary motor (M1), premotor (PMC) and supplementary motor cortices (SMA). DTI was used to define inter-hemispheric differences in the integrity of the corticospinal tracts projecting from M1. Clinical outcomes tested function (upper-extremity Fugl-Meyer (UEFM) and the perceived disability in the use of the paretic hand [Motor Activity Log (MAL)]. RESULTS Inter-hemispheric balance assessed with TMS relates differently to fMRI and DTI. Patients with high fMRI lateralization to the ipsilesional hemisphere possessed stronger ipsilesional corticomotor output maps [M1 (r=.831, p=.006), PMC (r=.797, p=.01)], and better balance of mutual transcallosal inhibition (r=.810, p=.015). Conversely, we have found that patients with less integrity of the corticospinal tracts in the ipsilesional hemisphere show greater corticospinal output of homologous tracts in the contralesional hemisphere (r=.850, p=.004). However, neither an imbalance in their integrity nor an imbalance of their output relates to

  15. (18)F and (18)FDG PET imaging of osteosarcoma to non-invasively monitor in situ changes in cellular proliferation and bone differentiation upon MYC inactivation.

    PubMed

    Arvanitis, Constadina; Bendapudi, Pavan K; Tseng, Jeffrey R; Gambhir, Sanjiv Sam; Felsher, Dean W

    2008-12-01

    Osteosarcoma is one of the most common pediatric cancers. Accurate imaging of osteosarcoma is important for proper clinical staging of the disease and monitoring of the tumor's response to therapy. The MYC oncogene has been commonly implicated in the pathogenesis of human osteosarcoma. Previously, we have described a conditional transgenic mouse model of MYC-induced osteosarcoma. These tumors are highly invasive and are frequently associated with pulmonary metastases. In our model, upon MYC inactivation osteosarcomas lose their neoplastic properties, undergo proliferative arrest and differentiate into mature bone. We reasoned that we could use our model system to develop noninvasive imaging modalities to interrogate the consequences of MYC inactivation on tumor cell biology in situ. We performed positron emission tomography (PET) combining the use of both (18)F-fluorodeoxyglucose ((18)FDG) and (18)F-flouride ((18)F) to detect metabolic activity and bone mineralization/remodeling. We found that upon MYC inactivation, tumors exhibited a slight reduction in uptake of (18)FDG and a significant increase in the uptake of (18)F along with associated histological changes. Thus, these cells have apparently lost their neoplastic properties based upon both examination of their histology and biologic activity. However, these tumors continue to accumulate (18)FDG at levels significantly elevated compared to normal bone. Therefore, PET can be used to distinguish normal bone cells from tumors that have undergone differentiation upon oncogene inactivation. In addition, we found that (18)F is a highly sensitive tracer for detection of pulmonary metastasis. Collectively, we conclude that combined modality PET/CT imaging incorporating both (18)FDG and (18)F is a highly sensitive means to non-invasively measure osteosarcoma growth and the therapeutic response, as well as to detect tumor cells that have undergone differentiation upon oncogene inactivation.

  16. 18F and 18FDG PET imaging of osteosarcoma to non-invasively monitor in situ changes in cellular proliferation and bone differentiation upon MYC inactivation

    PubMed Central

    Arvanitis, Constadina; Bendapudi, Pavan K.; Tseng, Jeffrey R.; Gambhir, Sanjiv Sam; Felsher, Dean W.

    2014-01-01

    Osteosarcoma is one of the most common pediatric cancers. Accurate imaging of osteosarcoma is important for proper clinical staging of the disease and monitoring of the tumor’s response to therapy. The MYC oncogene has been commonly implicated in the pathogenesis of human osteosarcoma. Previously, we have described a conditional transgenic mouse model of MYC-induced osteosarcoma. These tumors are highly invasive and are frequently associated with pulmonary metastases. In our model, upon MYC inactivation osteosarcomas lose their neoplastic properties, undergo proliferative arrest, and differentiate into mature bone. We reasoned that we could use our model system to develop noninvasive imaging modalities to interrogate the consequences of MYC inactivation on tumor cell biology in situ. We performed positron emission tomography (PET) combining the use of both 18F-fluorodeoxyglucose (18FDG) and 18F-flouride (18F) to detect metabolic activity and bone mineralization/remodeling. We found that upon MYC inactivation, tumors exhibited a slight reduction in uptake of 18FDG and a significant increase in the uptake of 18F along with associated histological changes. Thus, these cells have apparently lost their neoplastic properties based upon both examination of their histology and biologic activity. However, these tumors continue to accumulate 18FDG at levels significantly elevated compared to normal bone. Therefore, PET can be used to distinguish normal bone cells from tumors that have undergone differentiation upon oncogene inactivation. In addition, we found that 18F is a highly sensitive tracer for detection of pulmonary metastasis. Collectively, we conclude that combined modality PET/CT imaging incorporating both 18FDG and 18F is a highly sensitive means to non-invasively measure osteosarcoma growth and the therapeutic response, as well as to detect tumor cells that have undergone differentiation upon oncogene inactivation. PMID:18981708

  17. Non-invasive high-resolution tracking of human neuronal pathways: diffusion tensor imaging at 7T with 1.2 mm isotropic voxel size

    NASA Astrophysics Data System (ADS)

    Lützkendorf, Ralf; Hertel, Frank; Heidemann, Robin; Thiel, Andreas; Luchtmann, Michael; Plaumann, Markus; Stadler, Jörg; Baecke, Sebastian; Bernarding, Johannes

    2013-03-01

    Diffusion tensor imaging (DTI) allows characterizing and exploiting diffusion anisotropy effects, thereby providing important details about tissue microstructure. A major application in neuroimaging is the so-called fiber tracking where neuronal connections between brain regions are determined non-invasively by DTI. Combining these neural pathways within the human brain with the localization of activated brain areas provided by functional MRI offers important information about functional connectivity of brain regions. However, DTI suffers from severe signal reduction due to the diffusion-weighting. Ultra-high field (UHF) magnetic resonance imaging (MRI) should therefore be advantageous to increase the intrinsic signal-to-noise ratio (SNR). This in turn enables to acquire high quality data with increased resolution, which is beneficial for tracking more complex fiber structures. However, UHF MRI imposes some difficulties mainly due to the larger B1 inhomogeneity compared to 3T MRI. We therefore optimized the parameters to perform DTI at a 7 Tesla whole body MR scanner equipped with a high performance gradient system and a 32-channel head receive coil. A Stesjkal Tanner spin-echo EPI sequence was used, to acquire 110 slices with an isotropic voxel-size of 1.2 mm covering the whole brain. 60 diffusion directions were scanned which allows calculating the principal direction components of the diffusion vector in each voxel. The results prove that DTI can be performed with high quality at UHF and that it is possible to explore the SNT benefit of the higher field strength. Combining UHF fMRI data with UHF DTI results will therefore be a major step towards better neuroimaging methods.

  18. Belowground plant development measured with magnetic resonance imaging (MRI): exploiting the potential for non-invasive trait quantification using sugar beet as a proxy

    PubMed Central

    Metzner, Ralf; van Dusschoten, Dagmar; Bühler, Jonas; Schurr, Ulrich; Jahnke, Siegfried

    2014-01-01

    Both structural and functional properties of belowground plant organs are critical for the development and yield of plants but, compared to the shoot, much more difficult to observe due to soil opacity. Many processes concerning the belowground plant performance are not fully understood, in particular spatial and temporal dynamics and their interrelation with environmental factors. We used Magnetic Resonance Imaging (MRI) as a noninvasive method to evaluate which traits can be measured when a complex plant organ is monitored in-vivo while growing in the soil. We chose sugar beet (Beta vulgaris ssp. vulgaris) as a model system. The beet consists mainly of root tissues, is rather complex regarding tissue structure and responses to environmental factors, and thereby a good object to test the applicability of MRI for 3D phenotyping approaches. Over a time period of up to 3 months, traits such as beet morphology or anatomy were followed in the soil and the effect of differently sized pots on beet fresh weight calculated from MRI data was studied. There was a clear positive correlation between the pot size and the increase in fresh weight of a sugar beet over time. Since knowledge of the development of internal beet structures with several concentric cambia, vascular and parenchyma rings is still limited, we consecutively acquired 3D volumetric images on individual plants using the MRI contrast parameter T2 to map the development of rings at the tissue level. This demonstrates that MRI provides versatile protocols to non-invasively measure plant traits in the soil. It opens new avenues to investigate belowground plant performance under adverse environmental conditions such as drought, nutrient shortage, or soil compaction to seek for traits of belowground organs making plants more resilient to stress. PMID:25278947

  19. Belowground plant development measured with magnetic resonance imaging (MRI): exploiting the potential for non-invasive trait quantification using sugar beet as a proxy.

    PubMed

    Metzner, Ralf; van Dusschoten, Dagmar; Bühler, Jonas; Schurr, Ulrich; Jahnke, Siegfried

    2014-01-01

    Both structural and functional properties of belowground plant organs are critical for the development and yield of plants but, compared to the shoot, much more difficult to observe due to soil opacity. Many processes concerning the belowground plant performance are not fully understood, in particular spatial and temporal dynamics and their interrelation with environmental factors. We used Magnetic Resonance Imaging (MRI) as a noninvasive method to evaluate which traits can be measured when a complex plant organ is monitored in-vivo while growing in the soil. We chose sugar beet (Beta vulgaris ssp. vulgaris) as a model system. The beet consists mainly of root tissues, is rather complex regarding tissue structure and responses to environmental factors, and thereby a good object to test the applicability of MRI for 3D phenotyping approaches. Over a time period of up to 3 months, traits such as beet morphology or anatomy were followed in the soil and the effect of differently sized pots on beet fresh weight calculated from MRI data was studied. There was a clear positive correlation between the pot size and the increase in fresh weight of a sugar beet over time. Since knowledge of the development of internal beet structures with several concentric cambia, vascular and parenchyma rings is still limited, we consecutively acquired 3D volumetric images on individual plants using the MRI contrast parameter T2 to map the development of rings at the tissue level. This demonstrates that MRI provides versatile protocols to non-invasively measure plant traits in the soil. It opens new avenues to investigate belowground plant performance under adverse environmental conditions such as drought, nutrient shortage, or soil compaction to seek for traits of belowground organs making plants more resilient to stress.

  20. A non-invasive in vivo imaging system to study dissemination of bioluminescent Yersinia pestis CO92 in a mouse model of pneumonic plague

    PubMed Central

    Sha, Jian; Rosenzweig, Jason A.; Kirtley, Michelle L.; van Lier, Christina J.; Fitts, Eric C.; Kozlova, Elena V.; Erova, Tatiana E.; Tiner, Bethany L.; Chopra, Ashok K.

    2012-01-01

    The gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. This method, despite being quantitative, requires sacrificing the infected animals. Recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (IVIBB) for monitoring microbial dissemination within the host has been employed. Yersina pestis is a Gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. In this study, we compared the conventional counting of bacterial colony forming units (cfu) in the various infected tissues to IVIBB in monitoring Y. pestis dissemination in a mouse model of pneumonic plague. By using a transposon mutagenesis system harboring the luciferase (luc) gene, we screened approximately 4000 clones and obtained a fully virulent, luc-positive Y. pestis CO92 (Y. pestis-luc2) reporter strain in which transposition occurred within the largest pMT1 plasmid which possesses murine toxin and capsular antigen encoding genes. The aforementioned reporter strain and the wild-type CO92 exhibited similar growth curves, formed capsule based on immunofluorescence microscopy and flow cytometry, and had a similar LD50. Intranasal infection of mice with 15 LD50 of CO92-luc2 resulted in animal mortality by 72 h, and an increasing number of bioluminescent bacteria were observed in various mouse organs over a 24–72 h period when whole animals were imaged. However, following levofloxacin treatment (10 mg/kg/day) for 6 days 24 h post infection, no luminescence was observed after 72 h of infection, indicating that the tested antimicrobial killed bacteria preventing their detection in host peripheral tissues. Overall, we demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and our reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy of

  1. An advanced design of non-radioactive image capturing and management system for applications in non-invasive skin disorder diagnosis

    NASA Astrophysics Data System (ADS)

    Liu, Carol Y. B.; Luk, David C. K.; Zhou, Kany S. Y.; So, Bryan M. K.; Louie, Derek C. H.

    2015-03-01

    Due to the increasing incidences of malignant melanoma, there is a rising demand for assistive technologies for its early diagnosis and improving the survival rate. The commonly used visual screening method is with limited accuracy as the early phase of melanoma shares many clinical features with an atypical nevus, while conventional dermoscopes are not user-friendly in terms of setup time and operations. Therefore, the development of an intelligent and handy system to assist the accurate screening and long-term monitoring of melanocytic skin lesions is crucial for early diagnosis and prevention of melanoma. In this paper, an advanced design of non-invasive and non-radioactive dermoscopy system was reported. Computer-aided simulations were conducted for optimizing the optical design and uniform illumination distribution. Functional prototype and the software system were further developed, which could enable image capturing at 10x amplified and general modes, convenient data transmission, analysis of dermoscopic features (e.g., asymmetry, border irregularity, color, diameter and dermoscopic structure) for assisting the early detection of melanoma, extract patient information (e.g. code, lesion location) and integrate with dermoscopic images, thus further support long term monitoring of diagnostic analysis results. A clinical trial study was further conducted on 185 Chinese children (0-18 years old). The results showed that for all subjects, skin conditions diagnosed based on the developed system accurately confirmed the diagnoses by conventional clinical procedures. Besides, clinical analysis on dermoscopic features and a potential standard approach by the developed system to support identifying specific melanocytic patterns for dermoscopic examination in Chinese children were also reported.

  2. A non-invasive in vivo imaging system to study dissemination of bioluminescent Yersinia pestis CO92 in a mouse model of pneumonic plague.

    PubMed

    Sha, Jian; Rosenzweig, Jason A; Kirtley, Michelle L; van Lier, Christina J; Fitts, Eric C; Kozlova, Elena V; Erova, Tatiana E; Tiner, Bethany L; Chopra, Ashok K

    2013-02-01

    The gold standard in microbiology for monitoring bacterial dissemination in infected animals has always been viable plate counts. This method, despite being quantitative, requires sacrificing the infected animals. Recently, however, an alternative method of in vivo imaging of bioluminescent bacteria (IVIBB) for monitoring microbial dissemination within the host has been employed. Yersinia pestis is a Gram-negative bacterium capable of causing bubonic, septicemic, and pneumonic plague. In this study, we compared the conventional counting of bacterial colony forming units (cfu) in the various infected tissues to IVIBB in monitoring Y. pestis dissemination in a mouse model of pneumonic plague. By using a transposon mutagenesis system harboring the luciferase (luc) gene, we screened approximately 4000 clones and obtained a fully virulent, luc-positive Y. pestis CO92 (Y. pestis-luc2) reporter strain in which transposition occurred within the largest pMT1 plasmid which possesses murine toxin and capsular antigen encoding genes. The aforementioned reporter strain and the wild-type CO92 exhibited similar growth curves, formed capsule based on immunofluorescence microscopy and flow cytometry, and had a similar LD(50). Intranasal infection of mice with 15 LD(50) of CO92-luc2 resulted in animal mortality by 72 h, and an increasing number of bioluminescent bacteria were observed in various mouse organs over a 24-72 h period when whole animals were imaged. However, following levofloxacin treatment (10 mg/kg/day) for 6 days 24 h post infection, no luminescence was observed after 72 h of infection, indicating that the tested antimicrobial killed bacteria preventing their detection in host peripheral tissues. Overall, we demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and our reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy

  3. Raman molecular chemical imaging: 3D Raman using deconvolution

    NASA Astrophysics Data System (ADS)

    Maier, John S.; Treado, Patrick J.

    2004-12-01

    Chemical imaging is a powerful technique combining molecular spectroscopy and digital imaging for rapid, non-invasive and reagentless analysis of materials, including biological cells and tissues. Raman chemical imaging is suited to the characterization of molecular composition and structure of biomateials at submicron spatial resolution (< 250 nm). As a result, Raman imaging has potential as a routine tool for the assessment of cells and subcellular components. In this presentation, we discuss Raman chemical imaging and spectroscopy of single human cells obtained from a culture line. Rapid three dimensional Raman imaging is shown using deconvolution to improve image quality.

  4. Non-invasive ventilation.

    PubMed Central

    Spence, D.

    1996-01-01

    Nasal intermittent positive pressure ventilation is an effective treatment for nocturnal hypoventilation secondary to chest wall deformity or respiratory muscle weakness. Physicians should be aware that, in these groups of patients, disabling breathlessness can be alleviated and established cor pulmonale reversed by the technique. Images Figure 1 Figure 2 Figure 3 PMID:8949588

  5. CFD Modeling and Image Analysis of Exhaled Aerosols due to a Growing Bronchial Tumor: towards Non-Invasive Diagnosis and Treatment of Respiratory Obstructive Diseases

    SciTech Connect

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 µm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug de- livery protocol.

  6. CFD Modeling and Image Analysis of Exhaled Aerosols due to a Growing Bronchial Tumor: towards Non-Invasive Diagnosis and Treatment of Respiratory Obstructive Diseases

    SciTech Connect

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-02-06

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure vari-ations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagran-gian tracking approach were used to model respiratory airflows and aerosol dynamics. Respira-tions of tracer aerosols of 1 µm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug de-livery protocol.

  7. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    DOE PAGES

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; ...

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treatmore » the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 μm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.« less

  8. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    SciTech Connect

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 μm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.

  9. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: towards non-invasive diagnosis and treatment of respiratory obstructive diseases.

    PubMed

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A; Corley, Richard A; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 µm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.

  10. Potential of time series-hyperspectral imaging (TS-HSI) for non-invasive determination of microbial spoilage of salmon flesh.

    PubMed

    Wu, Di; Sun, Da-Wen

    2013-07-15

    This study investigated the potential of using time series-hyperspectral imaging (TS-HSI) in visible and near infrared region (400-1700 nm) for rapid and non-invasive determination of surface total viable count (TVC) of salmon flesh during spoilage process. Hyperspectral cubes were acquired at different spoilage stages for salmon chops and their spectral data were extracted. The reference TVC values of the same samples were measured using standard plate count method and then calibrated with their corresponding spectral data based on two calibration methods of partial least square regression (PLSR) and least-squares support vector machines (LS-SVM), respectively. Competitive adaptive reweighted sampling (CARS) was conducted to identify the most important wavelengths/variables that had the greatest influence on the TVC prediction throughout the whole wavelength range. As a result, eight variables representing the wavelengths of 495 nm, 535 nm, 550 nm, 585 nm, 625 nm, 660 nm, 785 nm, and 915 nm were selected, which were used to reduce the high dimensionality of the hyperspectral data. On the basis of the selected variables, the models of PLSR and LS-SVM were established and their performances were compared. The CARS-PLSR model established using Spectral Set I (400-1000 nm) was considered to be the best for the TVC determination of salmon flesh. The model led to a coefficient of determination (rP(2)) of 0.985 and residual predictive deviation (RPD) of 5.127. At last, the best model was used to predict the TVC values of each pixel within the ROI of salmon chops for visualizing the TVC distribution of salmon flesh. The research demonstrated that TS-HSI technique has a potential for rapid and non-destructive determination of bacterial spoilage in salmon flesh during the spoilage process. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. CFD Modeling and Image Analysis of Exhaled Aerosols due to a Growing Bronchial Tumor: towards Non-Invasive Diagnosis and Treatment of Respiratory Obstructive Diseases

    PubMed Central

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 µm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol. PMID:25767612

  12. Use of Non-Invasive Phase Contrast Magnetic Resonance Imaging for Estimation of Atrial Septal Defect Size and Morphology: A Comparison with Transesophageal Echo

    SciTech Connect

    Piaw, Chin Sze; Kiam, Ong Tiong; Rapaee, Annuar Khoon, Liew Chee; Bang, Liew Houng; Ling, Chan Wei; Samion, Hasri; Hian, Sim Kui

    2006-04-15

    Background: Transesophageal echocardiography (TEE) is a trusted method of sizing atrial septal defect (ASD) prior to percutaneous closure but is invasive, uncomfortable, and may carry a small risk of morbidity and mortality. Magnetic resonance imaging (MRI) may be useful non-invasive alternative in such patients who refuse or are unable to tolerate TEE and may provide additional information on the shape of the A0SD. Purpose: To validate the accuracy of ASD sizing by MRI compared with TEE.Method: Twelve patients (mean age 30 years; range 11-60 years) scheduled for ASD closure underwent TEE, cine balanced fast field echo MRI (bFFE-MRI) in four-chamber and sagittal views and phase-contrast MRI (PC-MRI) with reconstruction using the two orthogonal planes of T2-weighted images as planning. The average of the three longest measurements for all imaging modalities was calculated for each patient. Results: Mean maximum ASD length on TEE was 18.8 {+-} 4.6 mm, mean length by bFFE-MRI was 20.0 {+-} 5.0 mm, and mean length by PC-MRI was 18.3 {+-} 3.6 mm. The TEE measurement was significantly correlated with the bFFE-MRI and PC-MRI measurements (Pearson r = 0.69, p = 0.02 and r = 0.59, p = 0.04, respectively). The mean difference between TEE and bFFE-MRI measurements was -1.2mm (95% CI: -3.7, 1.3) and between TEE and PC-MRI was 0.5 mm (95% CI: -1.9, 2.9). Bland-Altman analysis also determined general agreement between both MRI methods and TEE. The ASDs were egg-shaped in two cases, circular in 1 patient and oval in the remaining patients. Conclusion: ASD sizing by MRI using bFFE and phase-contrast protocols correlated well with TEE estimations. PC-MRI provided additional information on ASD shapes and proximity to adjacent structures.

  13. Non-Invasive Imaging of Phosphoinositide-3-Kinase-Catalytic-Subunit-Alpha (PIK3CA) Promoter Modulation in Small Animal Models

    PubMed Central

    Gaikwad, Snehal M.; Gunjal, Lata; Junutula, Anitha R.; Astanehe, Arezoo; Gambhir, Sanjiv Sam; Ray, Pritha

    2013-01-01

    Activation of the PI3K/Akt pathway, a critical step for survival in cancer cells is often associated with decreased sensitivity to several chemotherapeutic drugs. PIK3CA gene amplification is observed in 16–24% of epithelial ovarian cancer (EOC) patients in conjunction with p53 mutations. A 900 bp long PIK3CA promoter is shown to be negatively regulated by p53 in ovarian surface epithelial cells but the consequence of chemotherapeutic drug treatments on this promoter in ovarian cancer cells is largely unknown. We aim to study the modulation of this promoter by cisplatin using an improved fusion reporter in ovarian cancer cells and tumor xenografts by non-invasive imaging approach. A PIK3CA sensor was developed using a bi-fusion reporter from a newly constructed library of bi- and tri-fusion vectors comprising of two mutant far red fluorescent proteins (mcherry/mch and tdTomato/tdt), a mutant firefly luciferase (fluc2), and a PET reporter protein (ttk). In vivo imaging of mice implanted with 293T cells transiently expressing these bi- and tri-fusion reporters along with respective controls revealed comparable activity of each reporter in the fusion background and fluc2-tdt as the most sensitive one. Repression of the PIK3CA sensor by drugs was inversely proportional to cellular p53 level in a germline (PA1) and in an EOC (A2780) cell line but not in a p53 deficient EOC (SKOV3) cell line. Bioluminescence imaging of tumor xenografts stably expressing the PIK3CA sensor in PA1 and A2780 cells exhibited attenuating activity without any change in SKOV3 tumors expressing the PIK3CA sensor after cisplatin treatment. Sequential mutation at p53 binding sites showed gradual increase in promoter activity and decreased effects of the drugs. These newly developed PIK3CA-fluc2-tdt and the mutant reporter sensors thus would be extremely useful for screening new drugs and for functional assessment of PIK3CA expression from intact cells to living subjects. PMID:23393606

  14. Feasibility of non-invasive temperature estimation by the assessment of the average gray-level content of B-mode images.

    PubMed

    Teixeira, C A; Alvarenga, A V; Cortela, G; von Krüger, M A; Pereira, W C A

    2014-08-01

    This paper assesses the potential of the average gray-level (AVGL) from ultrasonographic (B-mode) images to estimate temperature changes in time and space in a non-invasive way. Experiments were conducted involving a homogeneous bovine muscle sample, and temperature variations were induced by an automatic temperature regulated water bath, and by therapeutic ultrasound. B-mode images and temperatures were recorded simultaneously. After data collection, regions of interest (ROIs) were defined, and the average gray-level variation computed. For the selected ROIs, the AVGL-Temperature relation were determined and studied. Based on uniformly distributed image partitions, two-dimensional temperature maps were developed for homogeneous regions. The color-coded temperature estimates were first obtained from an AVGL-Temperature relation extracted from a specific partition (where temperature was independently measured by a thermocouple), and then extended to the other partitions. This procedure aimed to analyze the AVGL sensitivity to changes not only in time but also in space. Linear and quadratic relations were obtained depending on the heating modality. We found that the AVGL-Temperature relation is reproducible over successive heating and cooling cycles. One important result was that the AVGL-Temperature relations extracted from one region might be used to estimate temperature in other regions (errors inferior to 0.5 °C) when therapeutic ultrasound was applied as a heating source. Based on this result, two-dimensional temperature maps were developed when the samples were heated in the water bath and also by therapeutic ultrasound. The maps were obtained based on a linear relation for the water bath heating, and based on a quadratic model for the therapeutic ultrasound heating. The maps for the water bath experiment reproduce an acceptable heating/cooling pattern, and for the therapeutic ultrasound heating experiment, the maps seem to reproduce temperature profiles

  15. Non-invasive hemoglobin monitoring.

    PubMed

    Joseph, Bellal; Haider, Ansab; Rhee, Peter

    2016-09-01

    Technology has transformed the practice of medicine and surgery in particular over the last several decades. This change in practice has allowed diagnostic and therapeutic tests to be performed less invasively. Hemoglobin monitoring remains one of the most commonly performed diagnostic tests in the United States. Recently, non-invasive hemoglobin monitoring technology has gained popularity. The aim of this article is to review the principles of how this technology works, pros and cons, and the implications of non-invasive hemoglobin technology particularly in trauma surgery.

  16. The Non-Invasive Functional Tissue Characterization for Arteriosclerosis by Artery Wall Motion Analysis with Time Series High-Speed Echo Images and Continuous Spygmo-Manometer

    DTIC Science & Technology

    2007-11-02

    Abstract- The evaluation method of arteriosclerosis has been established, but most of them are invasive way. In late years, non-invasive diagnostic...method for arteriosclerosis can be done by the diagnosis with high resolution echography. However, even this new diagnostic method can not diagnose...until beginning the morphologic changes of the arteries by stenosis. There is little value even if it could be detected the arteriosclerosis after the

  17. Non-invasive methods for the determination of body and carcass composition in livestock: dual-energy X-ray absorptiometry, computed tomography, magnetic resonance imaging and ultrasound: invited review.

    PubMed

    Scholz, A M; Bünger, L; Kongsro, J; Baulain, U; Mitchell, A D

    2015-07-01

    The ability to accurately measure body or carcass composition is important for performance testing, grading and finally selection or payment of meat-producing animals. Advances especially in non-invasive techniques are mainly based on the development of electronic and computer-driven methods in order to provide objective phenotypic data. The preference for a specific technique depends on the target animal species or carcass, combined with technical and practical aspects such as accuracy, reliability, cost, portability, speed, ease of use, safety and for in vivo measurements the need for fixation or sedation. The techniques rely on specific device-driven signals, which interact with tissues in the body or carcass at the atomic or molecular level, resulting in secondary or attenuated signals detected by the instruments and analyzed quantitatively. The electromagnetic signal produced by the instrument may originate from mechanical energy such as sound waves (ultrasound - US), 'photon' radiation (X-ray-computed tomography - CT, dual-energy X-ray absorptiometry - DXA) or radio frequency waves (magnetic resonance imaging - MRI). The signals detected by the corresponding instruments are processed to measure, for example, tissue depths, areas, volumes or distributions of fat, muscle (water, protein) and partly bone or bone mineral. Among the above techniques, CT is the most accurate one followed by MRI and DXA, whereas US can be used for all sizes of farm animal species even under field conditions. CT, MRI and US can provide volume data, whereas only DXA delivers immediate whole-body composition results without (2D) image manipulation. A combination of simple US and more expensive CT, MRI or DXA might be applied for farm animal selection programs in a stepwise approach.

  18. In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans.

    PubMed

    Schneider, S; Feilen, P J; Schreckenberger, M; Schwanstecher, M; Schwanstecher, C; Buchholz, H G; Thews, O; Oberholzer, K; Korobeynikov, A; Bauman, A; Comagic, S; Piel, M; Schirrmacher, E; Shiue, C Y; Alavi, A A; Bartenstein, P; Rösch, F; Weber, M M; Klein, H H; Schirrmacher, R

    2005-07-01

    Pancreatic islet cell mass (PICM) is a major determinant of the insulin secretory capacity in humans. Currently, the only method for accurate assessment of the PICM is an autopsy study. Thus, development of a technique allowing the non-invasive quantification of PICM is of great interest. The aim of this study was to develop such a non-invasive technique featuring novel fluorine- and (99m)Tc-labelled glibenclamide derivatives. Despite the structural modifications necessary to introduce fluorine into the glibenclamide molecule, all derivatives retained insulin stimulating capacity as well as high affinity binding to human SUR1 when compared to the original glibenclamide. Contrastingly, the lipophilicity of the fluorine-labelled derivatives was altered depending on the particular modification. In the human PET-study a constant but weak radioactive signal could be detected in the pancreas using a fluorine-labelled glibenclamide derivative. However, a reliable assessment and visualisation of the PICM could not be obtained. It can be assumed that the high uptake of the fluorine-labelled tracer e.g. into the the liver and the high plasma protein binding leads to a relatively low signal-to-noise ratio. In case of the presented fluorine-labelled glibenclamide based compounds this could be the result of their invariably high lipophilicity. The development of a (99 m)Tc-labelled glibenclamide derivative with a lower lipophilicity and differing in vivo behaviour, glibenclamide based compounds for non-invasive imaging of the pancreatic islet cell mass may be possible.

  19. 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

  20. 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.

  1. Non-invasive evaluation of culprit lesions by PET imaging: shifting the clinical paradigm away from resultant anatomy toward causative physiology.

    PubMed

    Caobelli, Federico; Bengel, Frank M

    2014-12-01

    Although coronary angiography is the gold standard for assessing coronary artery disease (CAD), there is at best a weak correlation between degree of stenosis and the risk of developing cardiac events. Plaque rupture is the most common type of plaque complication, accounting for about 70% of fatal acute myocardial infarctions or sudden coronary deaths. Recently, the feasibility of (18)F-fluoride PET/CT in the evaluation of atherosclerotic lesions was assessed. Radionuclide techniques allow non-invasive biologic assessment of atherosclerotic plaques. This may help to further shift the clinical paradigm in coronary disease away from anatomy toward causative physiology and biology.

  2. Non-invasive evaluation of culprit lesions by PET imaging: shifting the clinical paradigm away from resultant anatomy toward causative physiology

    PubMed Central

    Bengel, Frank M.

    2014-01-01

    Although coronary angiography is the gold standard for assessing coronary artery disease (CAD), there is at best a weak correlation between degree of stenosis and the risk of developing cardiac events. Plaque rupture is the most common type of plaque complication, accounting for about 70% of fatal acute myocardial infarctions or sudden coronary deaths. Recently, the feasibility of 18F-fluoride PET/CT in the evaluation of atherosclerotic lesions was assessed. Radionuclide techniques allow non-invasive biologic assessment of atherosclerotic plaques. This may help to further shift the clinical paradigm in coronary disease away from anatomy toward causative physiology and biology. PMID:25610799

  3. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial

    PubMed Central

    Fayad, Zahi A; Mani, Venkatesh; Woodward, Mark; Kallend, David; Abt, Markus; Burgess, Tracy; Fuster, Valentin; Ballantyne, Christie M; Stein, Evan A; Tardif, Jean-Claude; Rudd, James H F; Farkouh, Michael E; Tawakol, Ahmed

    2014-01-01

    Summary Background Dalcetrapib modulates cholesteryl ester transfer protein (CETP) activity to raise high-density lipoprotein cholesterol (HDL-C). After the failure of torcetrapib it was unknown if HDL produced by interaction with CETP had pro-atherogenic or pro-inflammatory properties. dal-PLAQUE is the first multicentre study using novel non-invasive multimodality imaging to assess structural and inflammatory indices of atherosclerosis as primary endpoints. Methods In this phase 2b, double-blind, multicentre trial, patients (aged 18–75 years) with, or with high risk of, coronary heart disease were randomly assigned (1:1) to dalcetrapib 600 mg/day or placebo for 24 months. Randomisation was done with a computer-generated randomisation code and was stratified by centre. Patients and investigators were masked to treatment. Coprimary endpoints were MRI-assessed indices (total vessel area, wall area, wall thickness, and normalised wall index [average carotid]) after 24 months and 18F-fluorodeoxyglucose (18F-FDG) PET/CT assessment of arterial inflammation within an index vessel (right carotid, left carotid, or ascending thoracic aorta) after 6 months, with no-harm boundaries established before unblinding of the trial. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00655473. Findings 189 patients were screened and 130 randomly assigned to placebo (66 patients) or dalcetrapib (64 patients). For the coprimary MRI and PET/CT endpoints, CIs were below the no-harm boundary or the adverse change was numerically lower in the dalcetrapib group than in the placebo group. MRI-derived change in total vessel area was reduced in patients given dalcetrapib compared with those given placebo after 24 months; absolute change from baseline relative to placebo was −4·01 mm2 (90% CI −7·23 to −0·80; nominal p=0·04). The PET/CT measure of index vessel most-diseased-segment target-to-background ratio (TBR) was not different between groups

  4. Non-invasive neural stimulation

    NASA Astrophysics Data System (ADS)

    Tyler, William J.; Sanguinetti, Joseph L.; Fini, Maria; Hool, Nicholas

    2017-05-01

    Neurotechnologies for non-invasively interfacing with neural circuits have been evolving from those capable of sensing neural activity to those capable of restoring and enhancing human brain function. Generally referred to as non-invasive neural stimulation (NINS) methods, these neuromodulation approaches rely on electrical, magnetic, photonic, and acoustic or ultrasonic energy to influence nervous system activity, brain function, and behavior. Evidence that has been surmounting for decades shows that advanced neural engineering of NINS technologies will indeed transform the way humans treat diseases, interact with information, communicate, and learn. The physics underlying the ability of various NINS methods to modulate nervous system activity can be quite different from one another depending on the energy modality used as we briefly discuss. For members of commercial and defense industry sectors that have not traditionally engaged in neuroscience research and development, the science, engineering and technology required to advance NINS methods beyond the state-of-the-art presents tremendous opportunities. Within the past few years alone there have been large increases in global investments made by federal agencies, foundations, private investors and multinational corporations to develop advanced applications of NINS technologies. Driven by these efforts NINS methods and devices have recently been introduced to mass markets via the consumer electronics industry. Further, NINS continues to be explored in a growing number of defense applications focused on enhancing human dimensions. The present paper provides a brief introduction to the field of non-invasive neural stimulation by highlighting some of the more common methods in use or under current development today.

  5. Intravascular Targets for Molecular Contrast-Enhanced Ultrasound Imaging

    PubMed Central

    Moestue, Siver A.; Gribbestad, Ingrid S.; Hansen, Rune

    2012-01-01

    Molecular targeting of contrast agents for ultrasound imaging is emerging as a new medical imaging modality. It combines advances in ultrasound technology with principles of molecular imaging, thereby allowing non-invasive assessment of biological processes in vivo. Preclinical studies have shown that microbubbles, which provide contrast during ultrasound imaging, can be targeted to specific molecular markers. These microbubbles accumulate in tissue with target (over) expression, thereby significantly increasing the ultrasound signal. This concept offers safe and low-cost imaging with high spatial resolution and sensitivity. It is therefore considered to have great potential in cancer imaging, and early-phase clinical trials are ongoing. In this review, we summarize the current literature on targets that have been successfully imaged in preclinical models using molecularly targeted ultrasound contrast agents. Based on preclinical experience, we discuss the potential clinical utility of targeted microbubbles. PMID:22837657

  6. Special designed RF-antenna with integrated non-invasive carbon electrodes for simultaneous magnetic resonance imaging and electroencephalography acquisition at 7T.

    PubMed

    Van Audekerkea, J; Peeters, R; Verhoye, M; Sijbers, J; Van der Linden, A

    2000-09-01

    The construction of a high quality MR RF-antenna with incorporated EEG electrodes for simultaneous MRI and EEG acquisition is presented. The antenna comprises an active decoupled surface coil for receiving the MR signal and a whole body coil for transmitting the excitation RF pulses. The surface coil offers a high signal-to-noise ratio required for fMRI application and the whole body coil has a good B(1) excitation profile, which enables the application of homogeneous RF pulses. Non-invasive carbon electrodes are used in order to minimise the magnetic susceptibility artefacts that occur upon application of conductive materials. This dedicated set-up is compared to a standard set-up being a linear birdcage coil and commercially available Ag/AgCl electrodes. As the acquired EEG signals are heavily disturbed by the gradient switching, intelligent filtering is applied to obtain a clean EEG signal.

  7. PSMA-Targeted Nano-Conjugates as Dual-Modality (MRI/PET) Imaging Probes for the Non-Invasive Detection of Prostate Cancer

    DTIC Science & Technology

    2009-10-01

    include, bare AuNPs, polymer-coated AuNPs, gadolinium -coated AuNPs and polymer-coated Bi2S3. Molecular CT imaging of cancer using targeted AuNPs in cell...magnetically labeled cells with either gadolinium or iron oxide nanoparticle based agents.1–7 With the much larger ∗Author to whom correspondence...T2) than traditional gadolinium - based contrast agents (T1). However iron oxide based T2 agents also exhibit the inherent weakness of MRI contrast

  8. Preliminary results of a non-invasive method to measure tumor size and distribution in vivo

    PubMed Central

    Fu, Shu-Ling; Chen, Chien-An; Hung, Ling-Chien; Lee, Moon-Sing; Chiou, Wen-Yen; Lin, Hon-Yi; Su, Yu-Chieh; Lee, Ching-Chih; Hung, Shih-Kai

    2016-01-01

    Molecular imaging of reporter gene expression in cancer cells can provide rapid, sensitive and non-invasive monitoring of tumor behavior. The aim of the present study was to establish a non-invasive method to measure tumor size and distribution in vivo. Briefly, H-Ras-transformed cells were stably transfected with a plasmid containing the luciferase gene (Luc), designated as Ras/Luc. Ras/Luc cells were injected into the back or tail vein of nude BALB/cAnN-Foxn1nu/CrlNarl mice (age, 6–8 weeks). Mice were subsequently administered D-luciferin via intra-peritoneal injection, prior to image acquisition. Photons emitted from the mice were detected via an imaging system. Tumor size and distribution in vivo were quantified as photons/second. Andrographolide has demonstrated radiosensitization in previous in vitro and in vivo studies. In the present study, the potential effects of andrographolide cancer metastasis were investigated further, using an imaging system. Preliminary results of andrographolide combined with radiation indicated the inhibition of cancer metastasis. The present mechanistic study of andrographolide-mediated effects demonstrated that activated extracellular signal regulated kinase protein and H2O2 production levels were significantly increased by andrographolide. In summary, the present study established a non-invasive method to measure tumor size and distribution in vivo and indicated that andrographolide may be a potential therapeutic strategy in cancer therapy. PMID:28105095

  9. Non-invasive Evaluation for Epilepsy Surgery

    PubMed Central

    IWASAKI, Masaki; JIN, Kazutaka; NAKASATO, Nobukazu; TOMINAGA, Teiji

    2016-01-01

    Epilepsy surgery is aimed to remove the brain tissues that are indispensable for generating patient’s epileptic seizures. There are two purposes in the pre-operative evaluation: localization of the epileptogenic zone and localization of function. Surgery is planned to remove possible epileptogenic zone while preserving functional area. Since no single diagnostic modality is superior to others in identifying and localizing the epileptogenic zone, multiple non-invasive evaluations are performed to estimate the location of the epileptogenic zone after concordance between evaluations. Essential components of non-invasive pre-surgical evaluation of epilepsy include detailed clinical history, long-term video-electroencephalography monitoring, epilepsy-protocol magnetic resonance imaging (MRI), and neuropsychological testing. However, a significant portion of drug-resistant epilepsy is associated with no or subtle MRI lesions or with ambiguous electro-clinical signs. Additional evaluations including fluoro-deoxy glucose positron emission tomography (FDG-PET), magnetoencephalography and ictal single photon emission computed tomography can play critical roles in planning surgery. FDG-PET should be registered on three-dimensional MRI for better detection of focal cortical dysplasia. All diagnostic tools are complementary to each other in defining the epileptogenic zone, so that it is always important to reassess the data based on other results to pick up or confirm subtle abnormalities. PMID:27627857

  10. A comparison of non-invasive imaging modalities: Infrared thermography, spectrophotometric intracutaneous analysis and laser Doppler imaging for the assessment of adult burns.

    PubMed

    Burke-Smith, Alexandra; Collier, Jonathan; Jones, Isabel

    2015-12-01

    Currently, the only evidence-based adjunct to clinical evaluation of burn depth is laser Doppler imaging (LDI), although preliminary studies of alternative imaging modalities with instant image acquisition are promising. This is a study to investigate the accuracy of infrared thermography (IRT) and spectrophotometric intracutaneous analysis (SIA) for burn depth assessment, and compare this to the current gold standard: LDI. We include a comparison of the three modalities in terms of cost, reliability and usability. We recruited 20 patients with burns presenting to the Chelsea and Westminster Adult Burns Service. Between 48h and 5 days afterburn we recorded imaging using moorLDI2-BI-VR (LDI), FLIR E60 (IRT) and Scanoskin™ (SIA). Subsequent clinical management and outcome was as normal, and not affected by the extra images taken. 24 burn regions were grouped according to burn wound healing: group A healed within 14 days, group B within 14-21 days, and group C took more than 21 days or underwent grafting. Both LDI and IRT accurately determined healing potential in groups A and C, but failed to distinguish between groups B and C (p>0.05). Scanoskin™ interpretation of SIA was 100% consistent with clinical outcome. FLIR E60 and Scanoskin™ both present advantages to moorLDI2-BI-VR in terms of cost, ease-of-use and acceptability to patients. IRT is unlikely to challenge LDI as the gold standard as it is subject to the systematic bias of evaporative cooling. At present, the LDI colour-coded palette is the easiest method for image interpretation, whereas Scanoskin™ monochrome colour-palettes are more difficult to interpret. However the additional analyses of pigment available using SIA may help more accurately indicate the depth of burn compared with perfusion alone. We suggest development of Scanoskin™ software to include a simplified colour-palette similar to LDI and additional work to further investigate the potential of SIA as an alternative to the current gold

  11. An open source image processing method to quantitatively assess tissue growth after non-invasive magnetic resonance imaging in human bone marrow stromal cell seeded 3D polymeric scaffolds.

    PubMed

    Leferink, Anne M; Fratila, Raluca M; Koenrades, Maaike A; van Blitterswijk, Clemens A; Velders, Aldrik; Moroni, Lorenzo

    2014-01-01

    Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional (3D) scaffolds for regenerative medicine and clinical purposes. This is even more important when multipotent human bone marrow stromal cells (hMSCs) are used, as it could offer a method to understand in real time the dynamics of stromal cell differentiation and eventually steer it into the desired lineage. Magnetic Resonance Imaging (MRI) is a promising tool to overcome the challenge of a limited transparency in opaque 3D scaffolds. Technical limitations of MRI involve non-uniform background intensity leading to fluctuating background signals and therewith complicating quantifications on the retrieved images. We present a post-imaging processing sequence that is able to correct for this non-uniform background intensity. To test the processing sequence we investigated the use of MRI for in vitro monitoring of tissue growth in three-dimensional poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) scaffolds. Results showed that MRI, without the need to use contrast agents, is a promising non-invasive tool to quantitatively monitor ECM production and cell distribution during in vitro culture in 3D porous tissue engineered constructs.

  12. An Open Source Image Processing Method to Quantitatively Assess Tissue Growth after Non-Invasive Magnetic Resonance Imaging in Human Bone Marrow Stromal Cell Seeded 3D Polymeric Scaffolds

    PubMed Central

    Leferink, Anne M.; Fratila, Raluca M.; Koenrades, Maaike A.; van Blitterswijk, Clemens A.; Velders, Aldrik; Moroni, Lorenzo

    2014-01-01

    Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional (3D) scaffolds for regenerative medicine and clinical purposes. This is even more important when multipotent human bone marrow stromal cells (hMSCs) are used, as it could offer a method to understand in real time the dynamics of stromal cell differentiation and eventually steer it into the desired lineage. Magnetic Resonance Imaging (MRI) is a promising tool to overcome the challenge of a limited transparency in opaque 3D scaffolds. Technical limitations of MRI involve non-uniform background intensity leading to fluctuating background signals and therewith complicating quantifications on the retrieved images. We present a post-imaging processing sequence that is able to correct for this non-uniform background intensity. To test the processing sequence we investigated the use of MRI for in vitro monitoring of tissue growth in three-dimensional poly(ethylene oxide terephthalate)–poly(butylene terephthalate) (PEOT/PBT) scaffolds. Results showed that MRI, without the need to use contrast agents, is a promising non-invasive tool to quantitatively monitor ECM production and cell distribution during in vitro culture in 3D porous tissue engineered constructs. PMID:25502022

  13. Non-invasive glucose monitor

    NASA Technical Reports Server (NTRS)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2001-01-01

    A non-invasive method for determining blood level of an analyte of interest, such as glucose, comprises: generating an excitation laser beam (e.g., at a wavelength of 700 to 900 nanometers); focusing the excitation laser beam into the anterior chamber of an eye of the subject so that aqueous humor in the anterior chamber is illuminated; detecting (preferably confocally detecting) a Raman spectrum from the illuminated aqueous humor; and then determining the blood glucose level (or the level of another analyte of interest) for the subject from the Raman spectrum. Preferably, the detecting step is followed by the step of subtracting a confounding fluorescence spectrum from the Raman spectrum to produce a difference spectrum; and determining the blood level of the analyte of interest for the subject from that difference spectrum, preferably using linear or nonlinear multivariate analysis such as partial least squares analysis. Apparatus for carrying out the foregoing method is also disclosed.

  14. Diagnostic performance and comparative cost-effectiveness of non-invasive imaging tests in patients presenting with chronic stable chest pain with suspected coronary artery disease: a systematic overview.

    PubMed

    van Waardhuizen, Claudia N; Langhout, Marieke; Ly, Felisia; Braun, Loes; Genders, Tessa S S; Petersen, Steffen E; Fleischmann, Kirsten E; Nieman, Koen; Hunink, M G Myriam

    2014-01-01

    Several non-invasive imaging techniques are currently in use for the diagnostic workup of adult patients with stable chest pain suspected of having coronary artery disease (CAD). In this paper, we present a systematic overview of the evidence on diagnostic performance and comparative cost-effectiveness of new modalities in comparison to established technologies. A literature search for English language studies from 2009 to 2013 was performed, and two investigators independently extracted data on patient and study characteristics. The reviewed published evidence on diagnostic performance and cost-effectiveness support a strategy of CTCA as a rule out (gatekeeper) test of CAD in low- to intermediate-risk patients since it has excellent diagnostic performance and as initial imaging test is cost-effective under different willingness-to-pay thresholds. More cost-effectiveness research is needed in order to define the role and choice of cardiac stress imaging tests.

  15. Review of biomedical optical imaging—a powerful, non-invasive, non-ionizing technology for improving in vivo diagnosis

    NASA Astrophysics Data System (ADS)

    Balas, Costas

    2009-10-01

    This paper reviews the recent developments in the field of biomedical optical imaging, emphasizing technologies that have been moved from 'bench top to bedside'. Important new developments in this field allow for unprecedented visualization of the tissue microstructure and enable quantitative mapping of disease-specific endogenous and exogenous substances. With these advances, optical imaging technologies are becoming powerful clinical tools for non-invasive and objective diagnosis, guided treatment and monitoring therapies. Recent developments in visible and infrared diffuse spectroscopy and imaging, spectral imaging, optical coherence tomography, confocal imaging, molecular imaging and dynamic spectral imaging are presented together with their derivative medical devices. Their perspectives and challenges are discussed.

  16. Non-invasive high resolving power quantum microscope

    NASA Astrophysics Data System (ADS)

    Karmakar, Sanjit; Meyers, Ronald; Shih, Yanhua

    2013-09-01

    The development of a non-invasive high resolving power quantum microscope would further advance progress in research and development in biomedical and biosciences as well as the field of medical technology. Longer wavelengths, i.e visible or near-infrared, provide less invasive impact. On the other hand shorter wavelengths, i.e. UV, can provide better resolving power. That is why the development of a non-invasive high resolving power quantum microscope is critical. In this article, we propose such a microscope by using two-color entangled photon ghost imaging technology.

  17. Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features.

    PubMed

    Cho, Uiju; Mete, Ozgur; Kim, Min-Hee; Bae, Ja Seong; Jung, Chan Kwon

    2017-03-10

    Thyroid tumors formerly classified as non-invasive encapsulated follicular variant of papillary thyroid carcinoma were recently renamed 'non-invasive follicular thyroid neoplasm with papillary-like nuclear features'. The current study investigated the frequency of lymph node metastasis and mutational profile of encapsulated follicular variant in the setting of a clinical practice where central neck dissection was the standard of practice. We defined the impact of rigid diagnostic criteria by regrouping such tumors based on the complete absence of papillae or presence of ≤1% papillae. Of a total of 6,269 papillary thyroid carcinomas, 152 tumors fulfilled the criteria for encapsulated follicular variant. The results were stratified according to two different diagnostic cutoff criteria with respect to the extent of papillae. When the cutoff of 1% papillae was used, the rates of lymph node metastasis and BRAF(V600E) mutation were 3% and 10% in non-invasive tumors and 9% and 4% in invasive tumors, respectively. Despite the lack of invasive growth, one patient with BRAF(V600E) mutant-tumor displaying predominant follicular growth and subtle papillae developed a bone metastasis. When absence of papillary structure was applied as rigid diagnostic criteria, no BRAF(V600E) mutation was found in all tumors. However, central lymph node micrometastasis still occurred in 3% of non-invasive tumors. Non-V600E BRAF and RAS mutations were detected in 4% and 47% of non-invasive tumors, respectively. Our findings suggest that non-invasive follicular thyroid neoplasm with papillary-like nuclear features should not be regarded as a benign thyroid neoplasm as it can present with lymph node micrometastasis and should not be diagnosed in the presence of even a single papillary structure. Our findings underscore the original American Thyroid Association recommendation that defined non-invasive encapsulated follicular variants as low risk thyroid cancers. Clinical surveillance similar to

  18. Non-Invasive Glucose Measurement

    NASA Astrophysics Data System (ADS)

    Blakley, Daniel

    2010-10-01

    There are two little words, when taken together have great implications: ``What IF'' In the US alone, there are millions who are burdened with diabetes and who must maintain their glucose levels by taking blood samples and having it analyzed. Even though this procedure has improved over time, still it is very intrusive and is a burden to many that must live with it. What if it were not necessary? Although it is current practice to measure glucose levels invasively (using blood samples), it may be possible to measure glucose non-invasively. Although several companies around the world have invested millions of dollars to address this problem, none have been successful thus far. However, there are many methods that hold a potential and many approaches that have not yet been explored. We are working on a review of what has been approached thus far and are entertaining proposals for a combined interdisciplinary approach which combines expertise from bioengineering, physics, and biology. We hope to learn from the unsuccessful attempts of others whilst employing innovative new approaches to this problem.

  19. Molecular Optical Imaging with Radioactive Probes

    PubMed Central

    Liu, Hongguang; Ren, Gang; Miao, Zheng; Zhang, Xiaofen; Tang, Xiaodong; Han, Peizhen; Gambhir, Sanjiv S.; Cheng, Zhen

    2010-01-01

    Background Optical imaging (OI) techniques such as bioluminescence and fluorescence imaging have been widely used to track diseases in a non-invasive manner within living subjects. These techniques generally require bioluminescent and fluorescent probes. Here we demonstrate the feasibility of using radioactive probes for in vivo molecular OI. Methodology/Principal Findings By taking the advantages of low energy window of light (1.2–3.1 eV, 400–1000 nm) resulting from radiation, radionuclides that emit charged particles such as β+ and β− can be successfully imaged with an OI instrument. In vivo optical images can be obtained for several radioactive probes including 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), Na18F, Na131I, 90YCl3 and a 90Y labeled peptide that specifically target tumors. Conclusions/Significance These studies demonstrate generalizability of radioactive OI technique. It provides a new molecular imaging strategy and will likely have significant impact on both small animal and clinical imaging. PMID:20208993

  20. Preclinical evaluation of destruxin B as a novel Wnt signaling target suppressing proliferation and metastasis of colorectal cancer using non-invasive bioluminescence imaging

    SciTech Connect

    Yeh, Chi-Tai; Rao, Yerra Koteswara; Ye, Min; Wu, Wen-Shi; Chang, Tung-Chen; Wang, Liang-Shun; Wu, Chih-Hsiung; Wu, Alexander T.H.; Tzeng, Yew-Min

    2012-05-15

    In continuation to our studies toward the identification of direct anti-cancer targets, here we showed that destruxin B (DB) from Metarhizium anisopliae suppressed the proliferation and induced cell cycle arrest in human colorectal cancer (CRC) HT29, SW480 and HCT116 cells. Additionally, DB induced apoptosis in HT29 cells by decreased expression level of anti-apoptotic proteins Bcl-2 and Bcl-xL while increased pro-apoptotic Bax. On the other hand, DB attenuated Wnt-signaling by downregulation of β-catenin, Tcf4 and β-catenin/Tcf4 transcriptional activity, concomitantly with decreased expression of β-catenin target genes cyclin D1, c-myc and survivin. Furthermore, DB affected the migratory and invasive ability of HT29 cells through suppressed MMPs-2 and -9 enzymatic activities. We also found that DB targeted the MAPK and/or PI3K/Akt pathway by reduced expression of Akt, IKK-α, JNK, NF-κB, c-Jun and c-Fos while increased that of IκBα. Finally, we demonstrated that DB inhibited tumorigenesis in HT29 xenograft mice using non-invasive bioluminescence technique. Consistently, tumor samples from DB-treated mice demonstrated suppressed expression of β-catenin, cyclin D1, survivin, and endothelial marker CD31 while increased caspase-3 expression. Collectively, our data supports DB as an inhibitor of Wnt/β-catenin/Tcf signaling pathway that may be beneficial in the CRC management. Highlights: ► Destruxin B (DB) inhibited colorectal cancer cells growth and induced apoptosis. ► MAPK and/or PI3K/Akt cascade cooperates in DB induced apoptosis. ► DB affected the migratory and invasive ability of HT29 cells through MMP-9. ► DB attenuated Wnt-signaling components β-catenin, Tcf4. ► DB attenuated cyclin D1, c-myc, survivin and tumorigenesis in HT29 xenograft mice.

  1. Molecular Ultrasound Imaging: Current Status and Future Directions

    PubMed Central

    Deshpande, Nirupama; Needles, Andrew; Willmann, Jürgen K.

    2011-01-01

    Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionizing irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of preclinical and clinical ultrasound systems , the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic. PMID:20541656

  2. Molecular ultrasound imaging: current status and future directions.

    PubMed

    Deshpande, N; Needles, A; Willmann, J K

    2010-07-01

    Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionising irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of pre-clinical and clinical ultrasound systems, the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic. Copyright 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  3. Methods to monitor gene therapy with molecular imaging.

    PubMed

    Waerzeggers, Yannic; Monfared, Parisa; Viel, Thomas; Winkeler, Alexandra; Voges, Jürgen; Jacobs, Andreas H

    2009-06-01

    Recent progress in scientific and clinical research has made gene therapy a promising option for efficient and targeted treatment of several inherited and acquired disorders. One of the most critical issues for ensuring success of gene-based therapies is the development of technologies for non-invasive monitoring of the distribution and kinetics of vector-mediated gene expression. In recent years many molecular imaging techniques for safe, repeated and high-resolution in vivo imaging of gene expression have been developed and successfully used in animals and humans. In this review molecular imaging techniques for monitoring of gene therapy are described and specific use of these methods in the different steps of a gene therapy protocol from gene delivery to assessment of therapy response is illustrated. Linking molecular imaging (MI) to gene therapy will eventually help to improve the efficacy and safety of current gene therapy protocols for human application and support future individualized patient treatment.

  4. 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

  5. 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

  6. 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

  7. Molecular imaging in endoscopy

    PubMed Central

    Hoetker, Michael S

    2013-01-01

    Molecular imaging focuses on the molecular signature of cells rather than morphological changes in the tissue. The need for this novel type of imaging arises from the often difficult detection and characterization especially of small and/or premalignant lesions. Molecular imaging specifically visualizes biological properties of a lesion and might thereby be able to close diagnostic gaps, e.g. when differentiating hyperplastic from neoplastic polyps or detecting the margins of intraepithelial neoplastic spread. Additionally, not only the detection and discrimination of lesions could be improved: based on the molecular features identified using molecular imaging, therapy regimens could be adjusted on the day of diagnosis to allow for personalized medicine and optimized care for each individual patient. PMID:24917945

  8. Non-invasive physiology in conscious mice.

    PubMed

    Kale, Ajit; Amende, Ivo; Piskorski, Katrina; Chu, Victor; Otero, Jose M; Mueller, Peter; Hampton, Thomas G

    2004-06-01

    Linking gene defect to disease phenotypes in mice has become an essential step in the development of new drugs. Yet, many in vitro and in vivo assays require anaesthetic and surgery or do not reflect physiologically relevant phenomena. The effects of genes or diseases may only become apparent with stressors. Here, we apply non-invasive ECG monitoring and gait imaging systems to describe changes in the electrocardiogram and in gait dynamics resulting from a doubling of the ambulatory speed of mice. We found that B6C3H mice (n = 5) take 3.6 +/- 0.1 strides/second to walk 18cm/second and have a heart rate of 750 +/- 2bpm after 1 minute of walking at this speed. These mice significantly increase stride frequency to 5.2 +/- 0.1 strides/second in order to increase their speed to 36cm/second. The heart rate increased significantly (814 +/- 9bpm, p < 0.05) after trotting at the higher speed for 90 seconds, and the QRS interval duration significantly decreased (9.4 +/- 0.3ms vs. 10.4 +/- 0.3ms, p < 0.05). We discuss the application of the ECG screening and gait imaging systems to mouse models of Duchenne muscular dystrophy, Down syndrome and amyotrophic lateral sclerosis, diseases in humans that are known to affect the heart and neuromuscular systems.

  9. Novel non-invasive distribution measurement of texture profile analysis (TPA) in salmon fillet by using visible and near infrared hyperspectral imaging.

    PubMed

    Wu, Di; Sun, Da-Wen; He, Yong

    2014-02-15

    This study developed a pushbroom visible and near-infrared hyperspectral imaging system in the wavelength range of 400-1758 nm to determine the spatial distribution of texture profile analysis (TPA) parameters of salmon fillets. Six TPA parameters (hardness, adhesiveness, chewiness, springiness, cohesiveness, and gumminess) were analysed. Five spectral features (mean, standard deviation, skew, energy, and entropy) and 22 image texture features obtained from graylevel co-occurrence matrix (GLCM) were extracted from hyperspectral images. Quantitative models were established with the extracted spectral and image texture signatures of samples based on partial least squares regression (PLSR). The results indicated that spectral features had better ability to predict TPA parameters of salmon samples than image texture features, and Spectral Set I (400-1000 nm) performed better than Spectral II (967-1634 nm). On the basis of the wavelengths selected by regression coefficients of PLSR models, instrumental optimal wavelengths (IOW) and predictive optimal wavelengths (POW) were further chosen to reduce the high dimensionality of the hyperspectral image data. Our results show that hyperspectral imaging holds promise as a reliable and rapid alternative to traditional universal testing machines for measuring the spatial distribution of TPA parameters.

  10. High-field (11.75T) multimodal MR imaging of exercising hindlimb mouse muscles using a non-invasive combined stimulation and force measurement device.

    PubMed

    Gondin, Julien; Vilmen, Christophe; Cozzone, Patrick J; Bendahan, David; Duhamel, Guillaume

    2014-08-01

    We have designed and constructed an experimental set-up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high-field (11.75T). We performed high-resolution multimodal MRI (including T2 -weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1-week period to investigate the reliability of mechanical measurements and T2 changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T2 values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (≥0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high-field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions. Copyright © 2014 John Wiley & Sons, Ltd.

  11. Remote Non-invasive Stereoscopic Imaging of Blood Vessels: First In-vivo Results of a New Multispectral Contrast Enhancement Technology

    PubMed Central

    Mastik, F.; Cate, F. J. ten; Neumann, H. A. M.; van der Steen, A. F. W.

    2006-01-01

    We describe a contactless optical technique selectively enhancing superficial blood vessels below variously pigmented intact human skin by combining images in different spectral bands. Two CMOS-cameras, with apochromatic lenses and dual-band LED-arrays, simultaneously streamed Left (L) and Right (R) image data to a dual-processor PC. Both cameras captured color images within the visible range (VIS, 400–780 nm) and grey-scale images within the near infrared range (NIR, 910–920 nm) by sequentially switching between LED-array emission bands. Image-size-settings of 1280 × 1024 for VIS & 640 × 512 for NIR produced 12 cycles/s (1 cycle = 1 VIS L&R-pair + 1 NIR L&R-pair). Decreasing image-size-settings (640 × 512 for VIS and 320 × 256 for NIR) increased camera-speed to 25 cycles/s. Contrasts from below the tissue surface were algorithmically distinguished from surface shadows, reflections, etc. Thus blood vessels were selectively enhanced and back-projected into the stereoscopic VIS-color-image using either a 3D-display or conventional shutter glasses. As a first usability reconnaissance we applied this custom-built mobile stereoscopic camera for several clinical settings: • blood withdrawal; • vein inspection in dark skin; • vein detection through iodide; • varicose vein and nevi pigmentosum inspection. Our technique improves blood vessel visualization compared to the naked eye, and supports depth perception. PMID:17048103

  12. 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.

  13. Endothelial cell targeted molecular imaging in tumor angiogenesis: strategies and current status.

    PubMed

    Xu, Ye; Zeng, Yun; Liu, Yanhong; Liu, Gang; Ai, Hua

    2013-01-01

    Angiogenesis plays crucial roles in tumor growth, progression and metastasis. Non-invasive in vivo imaging of tumor neovasculature is a fundamental prerequisite for effective therapeutic intervention, particularly anti-angiogenic treatment regimens. Emerging molecular imaging techniques now allow recognition of cellular/molecular processes before gross pathological changes, leading to better understanding of fundamental biological processes of tumor angiogenesis. In this review, we will summarize recent progresses on molecular imaging of attractive biochemical epitopes in tumor angiogenesis, especially the endothelial cell targets-based imaging probes.

  14. Non-invasive ventilation for cystic fibrosis.

    PubMed

    Moran, Fidelma; Bradley, Judy M; Piper, Amanda J

    2017-02-20

    Non-invasive ventilation may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis by providing ventilatory support and avoiding tracheal intubation. Using non-invasive ventilation, in the appropriate situation or individuals, can improve lung mechanics through increasing airflow and gas exchange and decreasing the work of breathing. Non-invasive ventilation thus acts as an external respiratory muscle. This is an update of a previously published review. To compare the effect of non-invasive ventilation versus no non-invasive ventilation in people with cystic fibrosis for airway clearance, during sleep and during exercise. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials.Most recent search: 08 August 2016. Randomised controlled trials comparing a form of pressure preset or volume preset non-invasive ventilation to no non-invasive ventilation used for airway clearance or during sleep or exercise in people with acute or chronic respiratory failure in cystic fibrosis. Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. Ten trials met the inclusion criteria with a total of 191 participants. Seven trials evaluated single treatment sessions, one evaluated a two-week intervention, one evaluated a six-week intervention and one a three-month intervention. It is only possible to blind trials of airway clearance and overnight ventilatory support to the outcome assessors. In most of the trials we judged there was an unclear risk of bias with regards to blinding due to inadequate descriptions. The six-week trial was the only one judged to have a low risk of bias for all

  15. Non-invasive breast biopsy method using GD-DTPA contrast enhanced MRI series and F-18-FDG PET/CT dynamic image series

    NASA Astrophysics Data System (ADS)

    Magri, Alphonso William

    This study was undertaken to develop a nonsurgical breast biopsy from Gd-DTPA Contrast Enhanced Magnetic Resonance (CE-MR) images and F-18-FDG PET/CT dynamic image series. A five-step process was developed to accomplish this. (1) Dynamic PET series were nonrigidly registered to the initial frame using a finite element method (FEM) based registration that requires fiducial skin markers to sample the displacement field between image frames. A commercial FEM package (ANSYS) was used for meshing and FEM calculations. Dynamic PET image series registrations were evaluated using similarity measurements SAVD and NCC. (2) Dynamic CE-MR series were nonrigidly registered to the initial frame using two registration methods: a multi-resolution free-form deformation (FFD) registration driven by normalized mutual information, and a FEM-based registration method. Dynamic CE-MR image series registrations were evaluated using similarity measurements, localization measurements, and qualitative comparison of motion artifacts. FFD registration was found to be superior to FEM-based registration. (3) Nonlinear curve fitting was performed for each voxel of the PET/CT volume of activity versus time, based on a realistic two-compartmental Patlak model. Three parameters for this model were fitted; two of them describe the activity levels in the blood and in the cellular compartment, while the third characterizes the washout rate of F-18-FDG from the cellular compartment. (4) Nonlinear curve fitting was performed for each voxel of the MR volume of signal intensity versus time, based on a realistic two-compartment Brix model. Three parameters for this model were fitted: rate of Gd exiting the compartment, representing the extracellular space of a lesion; rate of Gd exiting a blood compartment; and a parameter that characterizes the strength of signal intensities. Curve fitting used for PET/CT and MR series was accomplished by application of the Levenburg-Marquardt nonlinear regression

  16. Wall Painting Investigation by Means of Non-invasive Terahertz Time-Domain Imaging (THz-TDI): Inspection of Subsurface Structures Buried in Historical Plasters

    NASA Astrophysics Data System (ADS)

    Dandolo, Corinna Ludovica Koch; Jepsen, Peter Uhd

    2016-02-01

    Characterization of subsurface features of wall paintings is important in conservation and technical art history as well as in building archaeology and architecture fields. In this study, an area of the apsidal wall painting of Nebbelunde Church (Rødby, Denmark) has been investigated by means of terahertz time-domain imaging (THz-TDI). Subsurface structures have been detected at different depths inside the lime-based plaster of the wall painting until approximately 1 cm from the surface. The surface morphology of the buried structures has been 3D imaged in detail, providing a substantial contribution in their characterization.

  17. Multimodal optical molecular image reconstruction with frequency domain measurements.

    PubMed

    Bartels, M; Chen, W; Bardhan, R; Ke, S; Halas, N J; Wareing, T; McGhee, J; Joshi, A

    2009-01-01

    Multimodality molecular imaging is becoming more and more important to understand both the structural and the functional characteristics of tissue, organs and tumors. So far, invasive nuclear methods utilizing ionizing radiation have been the "gold standard" of molecular imaging. We investigate non-contact, non-invasive, patient-tolerant and inexpensive near infrared (NIR) frequency domain optical tomography (FDOT) as a functional complement to structural X-ray computed tomography (CT) data. We show a novel multifrequency NIR FDOT approach both in transmission and reflectance mode and employ radiative transport equation (RTE) for 3D reconstruction of a target with novel fluorescent gold nanoshell indocyanine green (NS ICG) in an ex vivo nude mouse. The results demonstrate that gold NS ICG with multifrequency NIR FDOT is a promising fluorophore for multimodal optical molecular image reconstruction.

  18. Non-invasive diagnostic methods in dentistry

    NASA Astrophysics Data System (ADS)

    Todea, Carmen

    2016-03-01

    The paper, will present the most important non-invasive methods for diagnostic, in different fields of dentistry. Moreover, the laser-based methods will be emphasis. In orthodontics, 3D laser scanners are increasingly being used to establish database for normative population and cross-sectional growth changes but also to asses clinical outcomes in orthognatic surgical and non-surgical treatments. In prevention the main methods for diagnostic of demineralization and caries detection in early stages are represented by laser fluorescence - Quantitative Light Florescence (QLF); DiagnoDent-system-655nm; FOTI-Fiberoptic transillumination; DIFOTI-Digital Imaging Fiberoptic transillumination; and Optical Coherence Tomography (OCT). In odontology, Laser Doppler Flowmetry (LDF) is a noninvasive real time method used for determining the tooth vitality by monitoring the pulp microcirculation in traumatized teeth, fractured teeth, and teeth undergoing different conservative treatments. In periodontology, recently study shows the ability of LDF to evaluate the health of gingival tissue in periodontal tissue diseases but also after different periodontal treatments.

  19. 3D "spectracoustic" system: a modular, tomographic, spectroscopic mapping imaging, non-invasive, diagnostic system for detection of small starting developing tumors like melanoma

    NASA Astrophysics Data System (ADS)

    Karagiannis, Georgios

    2017-03-01

    This work led to a new method named 3D spectracoustic tomographic mapping imaging. The current and the future work is related to the fabrication of a combined acoustic microscopy transducer and infrared illumination probe permitting the simultaneous acquisition of the spectroscopic and the tomographic information. This probe provides with the capability of high fidelity and precision registered information from the combined modalities named spectracoustic information.

  20. A method to rapidly and accurately compare relative efficacies of non-invasive imaging reporter genes in a mouse model, and its application to luciferase reporters

    PubMed Central

    Gil, Jose S.; Machado, Hidevaldo B.; Herschman, Harvey R.

    2013-01-01

    Purpose Our goal is to develop a simple, quantitative, robust method to compare the efficacy of imaging reporter genes in culture and in vivo. We describe an adenoviral vector-liver transduction procedure, and compare the luciferase reporter efficacies. Procedures Alternative reporter genes are expressed in a common adenoviral vector. Vector amounts used in vivo are based on cell culture titrations, ensuring the same transduction efficacy is used for each vector. After imaging, in vivo and in vitro values are normalized to hepatic vector transduction using quantitative real-time PCR. Results We assayed standard firefly luciferase (FLuc), enhanced firefly luciferase (EFLuc), luciferase 2 (Luc2), humanized Renilla luciferase (hRLuc), Renilla luciferase 8.6-535 (RLuc8.6), and a membrane-bound Gaussia luciferase variant (extGLuc) in cell culture and in vivo. We observed a greater that 100-fold increase in bioluminescent signal for both EFLuc and Luc2 when compared to FLuc, and a greater than 106-fold increase for RLuc8.6 when compared to hRLuc. ExtGLuc was not detectable in liver. Conclusions Our findings contrast, in some cases, with conclusions drawn in prior comparisons of these reporter genes, and demonstrate the need for a standardized method to evaluate alternative reporter genes in vivo. Our procedure can be adapted for reporter genes that utilize alternative imaging modalities (fluorescence, bioluminescence, MRI, SPECT, PET). PMID:21850545

  1. Recent advances in molecular, multimodal and theranostic ultrasound imaging.

    PubMed

    Kiessling, Fabian; Fokong, Stanley; Bzyl, Jessica; Lederle, Wiltrud; Palmowski, Moritz; Lammers, Twan

    2014-06-01

    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 MBs 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.

  2. 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

  3. A method for recording resistance changes non-invasively during neuronal depolarization with a view to imaging brain activity with Electrical Impedance Tomography

    PubMed Central

    Gilad, Ori; Ghosh, Anthony; Oh, Dongin; Holder, David S

    2009-01-01

    Electrical Impedance Tomography (EIT) is a recently developed medical imaging method which has the potential to produce images of fast neuronal depolarization in the brain. The principle is that current remains in the extracellular space at rest but passes into the intracellular space during depolarization through open ion channels. As current passes into the intracellular space across the capacitance of cell membranes at higher frequencies, applied current needs to be below 100 Hz. A method is presented for its measurement with subtraction of the contemporaneous evoked potentials which occur in the same frequency band. Neuronal activity is evoked by stimulation and resistance is recorded from the potentials resulting from injection of a constant current square wave at 1 Hz with amplitude less than 25% of the threshold for stimulating neuronal activity. Potentials due to the evoked activity and the injected square wave are removed by subtraction. The method was validated with compound action potentials in crab walking leg nerve. Resistance changes of −0.85 ± 0.4 % (mean±SD) occurred which decreased from −0.97±0.43 % to −0.46±0.16 % with spacing of impedance current application electrodes from 2 to 8mm but did not vary significantly with applied currents of 1–10μA. These tallied with biophysical modelling, and so were consistent with a genuine physiological origin. This method appears to provide a reproducible and artefact free means for recording resistance changes during neuronal activity which could lead to the long-term goal of imaging of fast neural activity in the brain. PMID:19427534

  4. A novel endoscopic spectral imaging platform integrating k-means clustering for early and non-invasive diagnosis of endometrial pathology.

    PubMed

    Kavvadias, Vasileios; Epitropou, George; Georgiou, Nikos; Grozou, Fani; Paschopoulos, Minas; Balas, Costas

    2013-01-01

    We report a multimodal endoscopic system capable of performing both color and fast multispectral imaging in the spectral range 400-1000 nm. The system is based on a computer controllable tunable light source, which can be coupled with all types of endoscopes. Performance evaluation showed about 60% flat transmittance in almost all the operating wavelengths, at about 13 nm bandwidth per tuning step. With this system adapted to a thin hysteroscope, we also report, for the first time, spectral analysis of the endometrium and unsupervised/objective clustering of the spectra. We have implemented a method combining the k-means algorithm with the silhouette criterion for estimating the number of the distinguishable spectral classes that may correspond to different medical conditions of the tissue. It was found that there are five-well defined clusters of spectra, while preliminary clinical data seem to correlate well with the tissue pathology.

  5. A Novel Ideal Radionuclide Imaging System for Non-invasively Cell Monitoring built on Baculovirus Backbone by Introducing Sleeping Beauty Transposon

    PubMed Central

    Lv, Jing; Pan, Yu; Ju, Huijun; Zhou, Jinxin; Cheng, Dengfeng; Shi, Hongcheng; Zhang, Yifan

    2017-01-01

    Sleeping Beauty (SB) transposon is an attractive tool in stable transgene integration both in vitro and in vivo; and we introduced SB transposon into recombinant sodium-iodide symporter baculovirus system (Bac-NIS system) to facilitate long-term expression of recombinant sodium-iodide symporter. In our study, two hybrid baculovirus systems (Bac-eGFP-SB-NeoR and Bac-NIS-SB-NeoR) were successfully constructed and used to infect U87 glioma cells. After G418 selection screening, the Bac-eGFP-SB-NeoR-U87 cells remained eGFP positive, at the 18th and 196th day post transfection (96.03 ± 0.21% and 97.43 ± 0.81%), while eGFP positive population declined significantly at 18 days in cells transfected with unmodified baculovirus construct. NIS gene expression by Bac-NIS-SB-NeoR-U87 cells was also maintained for 28 weeks as determined by radioiodine uptake assay, reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot (WB) assay. When transplanted in mice, Bac-NIS-SB-NeoR-U87 cells also expressed NIS gene stably as monitored by SPECT imaging for 43 days until the tumor-bearing mice were sacrificed. Herein, we showed that incorporation of SB in Bac-NIS system (hybrid Bac-NIS-SB-NeoR) can achieve a long-term transgene expression and can improve radionuclide imaging in cell tracking and monitoring in vivo. PMID:28262785

  6. A Novel Ideal Radionuclide Imaging System for Non-invasively Cell Monitoring built on Baculovirus Backbone by Introducing Sleeping Beauty Transposon.

    PubMed

    Lv, Jing; Pan, Yu; Ju, Huijun; Zhou, Jinxin; Cheng, Dengfeng; Shi, Hongcheng; Zhang, Yifan

    2017-03-06

    Sleeping Beauty (SB) transposon is an attractive tool in stable transgene integration both in vitro and in vivo; and we introduced SB transposon into recombinant sodium-iodide symporter baculovirus system (Bac-NIS system) to facilitate long-term expression of recombinant sodium-iodide symporter. In our study, two hybrid baculovirus systems (Bac-eGFP-SB-NeoR and Bac-NIS-SB-NeoR) were successfully constructed and used to infect U87 glioma cells. After G418 selection screening, the Bac-eGFP-SB-NeoR-U87 cells remained eGFP positive, at the 18(th) and 196(th) day post transfection (96.03 ± 0.21% and 97.43 ± 0.81%), while eGFP positive population declined significantly at 18 days in cells transfected with unmodified baculovirus construct. NIS gene expression by Bac-NIS-SB-NeoR-U87 cells was also maintained for 28 weeks as determined by radioiodine uptake assay, reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot (WB) assay. When transplanted in mice, Bac-NIS-SB-NeoR-U87 cells also expressed NIS gene stably as monitored by SPECT imaging for 43 days until the tumor-bearing mice were sacrificed. Herein, we showed that incorporation of SB in Bac-NIS system (hybrid Bac-NIS-SB-NeoR) can achieve a long-term transgene expression and can improve radionuclide imaging in cell tracking and monitoring in vivo.

  7. Design of Experiments to Study the Impact of Process Parameters on Droplet Size and Development of Non-Invasive Imaging Techniques in Tablet Coating.

    PubMed

    Dennison, Thomas J; Smith, Julian; Hofmann, Michael P; Bland, Charlotte E; Badhan, Raj K; Al-Khattawi, Ali; Mohammed, Afzal R

    2016-01-01

    Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats.

  8. Design of Experiments to Study the Impact of Process Parameters on Droplet Size and Development of Non-Invasive Imaging Techniques in Tablet Coating

    PubMed Central

    Dennison, Thomas J.; Smith, Julian; Hofmann, Michael P.; Bland, Charlotte E.; Badhan, Raj K.; Al-Khattawi, Ali; Mohammed, Afzal R.

    2016-01-01

    Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats. PMID:27548263

  9. Molecular Imaging Without Radiopharmaceuticals?

    PubMed Central

    Gore, John C.; Yankeelov, Thomas E.; Peterson, Todd. E.; Avison, Malcolm J.

    2009-01-01

    The limitations on the sensitivity for detecting small changes in MRI, CT, and ultrasound pulse-echo images are used to estimate the practical requirements for molecular imaging and targeted contrast enhancement for these modalities. These types of imaging are highly unlikely to approach the sensitivity for detecting molecular processes of radionuclear methods, and the prospects for achieving sufficient concentrations of appropriate agents in vivo are poor for several types of applications such as small-molecule targeting of specific receptors. However, using relatively large carrier systems such as particles and liposomes, sufficient concentrations of paramagnetic agents may be delivered to achieve MR-signal changes adequate for detection. The use of higher-resolution MR images will aid the prospects for molecular imaging in small animals. Theoretic considerations also predict that a similar approach, using rather large particles or carriers of materials with a high atomic number, may also be successful for CT, especially with additional developments such as the use of monochromatic x-rays. The prospects of molecular imaging by x-ray imaging may not be as bleak as has been predicted. For ultrasound detection, gas-filled bubbles can provide a sufficient backscattered sound intensity to be detectable at concentrations and sizes not much different from agents designed for these other modalities. PMID:19443583

  10. Non-invasive sensing for food reassurance.

    PubMed

    Xiaobo, Zou; Xiaowei, Huang; Povey, Malcolm

    2016-03-07

    Consumers and governments are increasingly interested in the safety, authenticity and quality of food commodities. This has driven attention towards non-invasive sensing techniques used for rapid analyzing these commodities. This paper provides an overview of the state of the art in, and available alternatives for, food assurance based on non-invasive sensing techniques. The main food quality traits of interest using non-invasive sensing techniques are sensory characteristics, chemical composition, physicochemical properties, health-protecting properties, nutritional characteristics and safety. A wide range of non-invasive sensing techniques, from optical, acoustical, electrical, to nuclear magnetic, X-ray, biosensor, microwave and terahertz, are organized according to physical principle. Some of these techniques are now in a period of transition between experimental and applied utilization and several sensors and instruments are reviewed. With continued innovation and attention to key challenges, such non-invasive sensors and biosensors are expected to open up new exciting avenues in the field of portable and wearable wireless sensing devices and connecting with mobile networks, thus finding considerable use in a wide range of food assurance applications. The need for an appropriate regulatory framework is emphasized which acts to exclude unwanted components in foods and includes needed components, with sensors as part of a reassurance framework supporting regulation and food chain management. The integration of these sensor modalities into a single technological and commercial platform offers an opportunity for a paradigm shift in food reassurance.

  11. Non-invasive diagnostic workup of patients with suspected stable angina by combined computed tomography coronary angiography and magnetic resonance perfusion imaging.

    PubMed

    Kirschbaum, Sharon W; Nieman, Koen; Springeling, Tirza; Weustink, Annick C; Ramcharitar, Steve; Mieghem, Carlos van; Rossi, Alexia; Duckers, Eric; Serruys, Patrick W; Boersma, Eric; de Feyter, Pim J; van Geuns, Robert-Jan M

    2011-01-01

    To evaluate additional adenosine magnetic resonance perfusion (MRP) imaging in the diagnostic workup of patients with suspected stable angina with computed tomography coronary angiography (CTCA) as first-line diagnostic modality. Two hundred and thirty symptomatic patients (male, 52%; age, 56 year) with suspected stable angina underwent CTCA. In patients with a stenosis of >50% as visually assessed, MRP was performed and the quantitative myocardial perfusion reserve index (MPRI) was calculated. Coronary flow reserve (CFR) using invasive coronary flow measurements served as the standard of reference. CTCA showed non-significant CAD in 151/230 (66%) patients and significant CAD in 79/230 patients (34%), of whom 50 subsequently underwent MRP and CFR. MRP showed reduced perfusion in 32 patients (64%), which was confirmed by CFR in 27 (84%). All 18 cases of normal MRP (36%) were confirmed by CFR. The positive likelihood ratio of MRP for the presence of functional significant disease in patients with a lesion on CTCA was 4.49 (95% confidence interval [CI] 2.12-9.99). The negative likelihood ratio was 0.05 (95%CI 0.01-0.34). CTCA as first-line diagnostic modality excluded coronary artery disease in a high percentage of patients referred for diagnostic workup of suspected stable angina. MRP made a significant contribution to the detection of functional significant lesions in patients with a positive CTCA.

  12. Probing the in vivo changes in oxygen saturation with photoacoustic imaging as a non-invasive means of assessing treatment progression

    NASA Astrophysics Data System (ADS)

    Hysi, Eno; May, Jonathan P.; Wirtzfeld, Lauren; Undzys, Elijus; Li, Shyh-Dar; Kolios, Michael C.

    2015-03-01

    In vivo photoacoustic estimations of tumor oxygenation were used to assess the therapeutic efficacy of a thermosensitive liposome treatment in a pre-clinical mouse model. The treated group (n = 12) was administered doxorubicin-loaded, heat sensitive liposomes and exposed to mild hyperthermia (43°C) in order to deliver doxorubicin locally within the tumor micro-vessels. Control groups received systemic doxorubicin (n = 7) or saline (n = 12). The changes in tumor blood vessels after treatment were probed by analyzing the frequency content of the photoacoustic radiofrequency signals. Tumor oxygenation dropped by 15-20% during the first 30 minutes post-treatment when the tumors were exposed to encapsulated (Heat-Activated cyToxic - HaT-DOX) or free doxorubicin (DOX). The early (30 minutes to 5 hours) decrease in oxygen saturation strongly correlated to the reduction in tumor size assessed by caliper measurements. Control animals did not exhibit significant changes in tumor oxygenation at the early time points. The oxygenation at 7 days increased significantly for all groups. Measurements of the spectral slope from the normalized power spectra of the photoacoustic signals could also be used to differentiate between responder and non-responder mice. The results of this study suggest that photoacoustic imaging of tumors undergoing vascular-targeted cancer therapy can be used to assess treatment response early (hours) post-treatment through a combined analysis of oxygen saturation and photoacoustic radiofrequency spectroscopy.

  13. Molecular Imaging System for Monitoring Tumor Angiogenesis

    NASA Astrophysics Data System (ADS)

    Aytac, Esra; Burcin Unlu, Mehmet

    2012-02-01

    In cancer, non-invasive imaging techniques that monitor molecular processes associated with the tumor angiogenesis could have a central role in the evaluation of novel antiangiogenic and proangiogenic therapies as well as early detection of the disease. Matrix metalloproteinases (MMP) can serve as specific biological targets for imaging of angiogenesis since expression of MMPs is required for angiogenesis and has been found to be upregulated in every type of human cancer and correlates with stage, invasive, metastatic properties and poor prognosis. However, for most cancers it is still unknown when, where and how MMPs are involved in the tumor angiogenesis [1]. Development of high-resolution, high sensitivity imaging techniques in parallel with the tumor models could prove invaluable for assessing the physical location and the time frame of MMP enzymatic acitivity. The goal of this study is to understand where, when and how MMPs are involved in the tumor angiogenesis. We will accomplish this goal by following two objectives: to develop a high sensitivity, high resolution molecular imaging system, to develop a virtual tumor simulator that can predict the physical location and the time frame of the MMP activity. In order to achieve our objectives, we will first develop a PAM system and develop a mathematical tumor model in which the quantitative data obtained from the PAM can be integrated. So, this work will develop a virtual tumor simulator and a molecular imaging system for monitoring tumor angiogenesis. 1.Kessenbrock, K., V. Plaks, and Z. Werb, MMP:regulators of the tumor microenvironment. Cell, 2010. 141(1)

  14. Non-Invasive Imaging Provides Spatiotemporal Information on Disease Progression and Response to Therapy in a Murine Model of Multiple Myeloma

    PubMed Central

    Riedel, Simone S.; Mottok, Anja; Brede, Christian; Bäuerlein, Carina A.; Jordán Garrote, Ana-Laura; Ritz, Miriam; Mattenheimer, Katharina; Rosenwald, Andreas; Einsele, Hermann; Bogen, Bjarne; Beilhack, Andreas

    2012-01-01

    Background Multiple myeloma (MM) is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy. Material and Methods A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM) that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI). Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology. Results Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells. Conclusions This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This

  15. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

    PubMed Central

    Mostafa, Heba H.; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J.

    2016-01-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

  16. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.

    PubMed

    Mostafa, Heba H; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J

    2016-09-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus-specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential.

  17. Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development

    PubMed Central

    Girardi, G; Fraser, J; Lennen, R; Vontell, R; Jansen, M; Hutchison, G

    2015-01-01

    In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders. PMID:25245499

  18. Molecular Imaging: A Useful Tool for the Development of Natural Killer Cell-Based Immunotherapies.

    PubMed

    Gangadaran, Prakash; Ahn, Byeong-Cheol

    2017-01-01

    Molecular imaging is a relatively new discipline that allows visualization, characterization, and measurement of the biological processes in living subjects, including humans, at a cellular and molecular level. The interaction between cancer cells and natural killer (NK) cells is complex and incompletely understood. Despite our limited knowledge, progress in the search for immune cell therapies against cancer could be significantly improved by dynamic and non-invasive visualization and tracking of immune cells and by visualization of the response of cancer cells to therapies in preclinical and clinical studies. Molecular imaging is an essential tool for these studies, and a multimodal molecular imaging approach can be applied to monitor immune cells in vivo, for instance, to visualize therapeutic effects. In this review, we discuss the usefulness of NK cells in cancer therapies and the preclinical and clinical usefulness of molecular imaging in NK cell-based therapies. Furthermore, we discuss different molecular imaging modalities for use with NK cell-based therapies, and their preclinical and clinical applications in animal and human subjects. Molecular imaging has contributed to the development of NK cell-based therapies against cancers in animal models and to the refinement of current cell-based cancer immunotherapies. Developing sensitive and reproducible non-invasive molecular imaging technologies for in vivo NK cell monitoring and for real-time assessment of therapeutic effects will accelerate the development of NK cell therapies.

  19. Non-invasive characterization of structure and morphology of silk fibroin biomaterials using non-linear microscopy

    PubMed Central

    Rice, William L.; Firdous, Shamaraz; Gupta, Sharad; Hunter, Martin; Foo, Cheryl Wong Po; Wang, Yongzhong; Kim, Hyeon Joo; Kaplan, David L.; Georgakoudi, Irene

    2009-01-01

    Designing biomaterial scaffolds remains a major challenge in tissue engineering. Key to this challenge is improved understanding of the relationships between the scaffold properties and its degradation kinetics, as well as the cell interactions and the promotion of new matrix deposition. Here we present the use of non-linear spectroscopic imaging as a non-invasive method to characterize not only morphological, but also structural aspects of silkworm silk fibroin-based biomaterials, relying entirely on endogenous optical contrast. We demonstrate that two photon excited fluorescence and second harmonic generation are sensitive to the hydration, overall β sheet content and molecular orientation of the sample. Thus, the functional content and high resolution afforded by these non-invasive approaches offer promise for identifying important connections between biomaterial design and functional engineered tissue development. The strategies described also have broader implications for understanding and tracking the remodeling of degradable biomaterials under dynamic conditions both in vitro and in vivo. PMID:18291520

  20. Hepatic steatosis and fibrosis: Non-invasive assessment

    PubMed Central

    Karanjia, Rustam N; Crossey, Mary M E; Cox, I Jane; Fye, Haddy K S; Njie, Ramou; Goldin, Robert D; Taylor-Robinson, Simon D

    2016-01-01

    Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy. PMID:28018096

  1. Non-invasive assessments of adipose tissue metabolism in vitro

    PubMed Central

    Abbott, Rosalyn D.; Borowsky, Francis E.; Quinn, Kyle P.; Bernstein, David L.; Georgakoudi, Irene; Kaplan, David L.

    2015-01-01

    Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with noninvasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored. PMID:26399988

  2. Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging.

    PubMed

    Hildreth, Blake Eason; Williams, Michelle M; Dembek, Katarzyna A; Hernon, Krista M; Rosol, Thomas J; Toribio, Ramiro E

    2015-12-01

    Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and µCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.

  3. Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging

    PubMed Central

    Hildreth, Blake Eason; Williams, Michelle C.; Dembek, Katarzyna A.; Hernon, Krista M.; Rosol, Thomas J.; Toribio, Ramiro E.

    2015-01-01

    Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone (PTH) 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and μCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and 1) total bioluminescence (r = 0.595; P = 0.019); 2) total fluorescence (r = 0.474; P = 0.074); and 3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI. PMID:26271486

  4. Non-invasive in vivo imaging of cardiac stem/progenitor cell biodistribution and retention after intracoronary and intramyocardial delivery in a swine model of chronic ischemia reperfusion injury.

    PubMed

    Collantes, María; Pelacho, Beatriz; García-Velloso, María José; Gavira, Juán José; Abizanda, Gloria; Palacios, Itziar; Rodriguez-Borlado, Luis; Álvarez, Virginia; Prieto, Elena; Ecay, Margarita; Larequi, Eduardo; Peñuelas, Iván; Prósper, Felipe

    2017-03-13

    The safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure. However, their optimal delivery route to the ischemic heart has not yet been assessed. This study was designed to determine by a non-invasive imaging technique (PET/CT) the biodistribution and acute retention of allogeneic pig CSC implanted by two different delivery routes, intracoronary (IC) and intramyocardial (IM), in a swine preclinical model of chronic ischemia-reperfusion. Ischemia-reperfusion was induced in six Goettingen hybrid minipigs by 90 min coronary artery occlusion followed by reperfusion. Thirty days later, animals were allocated to receive IC (n = 3) or NOGA(®)-guided IM injection (n = 3) of 50 million of (18)F-FDG/GFP-labeled allogeneic pig CSC. Acute retention was quantified by PET/CT 4 h after injection and cell engraftment assessed by immunohistochemical quantification of GFP(+) cells three days post-injection. Biodistribution of (18)F-FDG-labeled CSC was clearly visualized by PET/CT imaging and quantified. No statistical differences in acute cell retention (percentage of injected dose, %ID) were found in the heart when cells were administered by NOGA(®)-guided IM (13.4 ± 3.4%ID) or IC injections (17.4 ± 4.1%ID). Interestingly, engrafted CSC were histologically detected only after IM injection. PET/CT imaging of (18)F-FDG-labeled CSC allows quantifying biodistribution and acute retention of implanted cells in a clinically relevant pig model of chronic myocardial infarction. Similar levels of acute retention are achieved when cells are IM or IC administered. However, acute cell retention does not correlate with cell engraftment, which is improved by IM injection.

  5. Molecular imaging and cancer gene therapy.

    PubMed

    Saadatpour, Z; Bjorklund, G; Chirumbolo, S; Alimohammadi, M; Ehsani, H; Ebrahiminejad, H; Pourghadamyari, H; Baghaei, B; Mirzaei, H R; Sahebkar, A; Mirzaei, H; Keshavarzi, M

    2016-11-18

    Gene therapy is known as one of the most advanced approaches for therapeutic prospects ranging from tackling genetic diseases to combating cancer. In this approach, different viral and nonviral vector systems such as retrovirus, lentivirus, plasmid and transposon have been designed and employed. These vector systems are designed to target different therapeutic genes in various tissues and cells such as tumor cells. Therefore, detection of the vectors containing therapeutic genes and monitoring of response to the treatment are the main issues that are commonly faced by researchers. Imaging techniques have been critical in guiding physicians in the more accurate and precise diagnosis and monitoring of cancer patients in different phases of malignancies. Imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are non-invasive and powerful tools for monitoring of the distribution of transgene expression over time and assessing patients who have received therapeutic genes. Here, we discuss most recent advances in cancer gene therapy and molecular approaches as well as imaging techniques that are utilized to detect cancer gene therapeutics and to monitor the patients' response to these therapies worldwide, particularly in Iranian Academic Medical Centers and Hospitals.Cancer Gene Therapy advance online publication, 18 November 2016; doi:10.1038/cgt.2016.62.

  6. Radionuclide imaging - A molecular key to the atherosclerotic plaque

    PubMed Central

    Langer, Harald Franz; Haubner, Roland; Pichler, Bernd Juergen; Gawaz, Meinrad

    2008-01-01

    Despite primary and secondary prevention, serious cardiovascular events like unstable angina or myocardial infarction still account for one third of all deaths worldwide. Therefore, identifying individual patients with vulnerable plaques at high risk for plaque rupture is a central challenge in cardiovascular medicine. Several non-invasive techniques, such as MRI, multislice computed tomography and electron beam tomography are currently being tested for their ability to identify such patients by morphological criteria. In contrast, molecular imaging techniques use radiolabeled molecules to detect functional aspects in atherosclerotic plaques by visualizing its biological activity. Based upon the knowledge about the pathophysiology of atherosclerosis, various studies in vitro, in vivo and the first clinical trials have used different tracers for plaque imaging studies, including radioactive labelled lipoproteins, components of the coagulation system, cytokines, mediators of the metalloproteinase system, cell adhesion receptors and even whole cells. This review gives an update on the relevant non-invasive plaque imaging approaches using nuclear imaging techniques to detect atherosclerotic vascular lesions. PMID:18582628

  7. Nanobody: The “Magic Bullet” for Molecular Imaging?

    PubMed Central

    Chakravarty, Rubel; Goel, Shreya; Cai, Weibo

    2014-01-01

    Molecular imaging involves the non-invasive investigation of biological processes in vivo at the cellular and molecular level, which can play diverse roles in better understanding and treatment of various diseases. Recently, single domain antigen-binding fragments known as 'nanobodies' were bioengineered and tested for molecular imaging applications. Small molecular size (~15 kDa) and suitable configuration of the complementarity determining regions (CDRs) of nanobodies offer many desirable features suitable for imaging applications, such as rapid targeting and fast blood clearance, high solubility, high stability, easy cloning, modular nature, and the capability of binding to cavities and difficult-to-access antigens. Using nanobody-based probes, several imaging techniques such as radionuclide-based, optical and ultrasound have been employed for visualization of target expression in various disease models. This review summarizes the recent developments in the use of nanobody-based probes for molecular imaging applications. The preclinical data reported to date are quite promising, and it is expected that nanobody-based molecular imaging agents will play an important role in the diagnosis and management of various diseases. PMID:24578722

  8. Non-invasive monitoring of spreading depression.

    PubMed

    Bastany, Zoya J R; Askari, Shahbaz; Dumont, Guy A; Speckmann, Erwin-Josef; Gorji, Ali

    2016-10-01

    Spreading depression (SD), a slow propagating depolarization wave, plays an important role in pathophysiology of different neurological disorders. Yet, research into SD-related disorders has been hampered by the lack of non-invasive recording techniques of SD. Here we compared the manifestations of SD in continuous non-invasive electroencephalogram (EEG) recordings to invasive electrocorticographic (ECoG) recordings in order to obtain further insights into generator structures and electrogenic mechanisms of surface recording of SD. SD was induced by KCl application and simultaneous SD recordings were performed by scalp EEG as well as ECoG electrodes of somatosensory neocortex of rats using a novel homemade EEG amplifier, AgCl recording electrodes, and high chloride conductive gel. Different methods were used to analyze the data; including the spectrogram, bi-spectrogram, pattern distribution, relative spectrum power, and multivariable Gaussian fit analysis. The negative direct current (DC) shifts recorded by scalp electrodes exhibited a high homogeneity to those recorded by ECoG electrodes. Furthermore, this novel method of recording and analysis was able to separate SD recorded by scalp electrodes from non-neuronal DC shifts induced by other potential generators, such as the skin, muscles, arteries, dura, etc. These data suggest a novel application for continuous non-invasive monitoring of DC potential changes, such as SD. Non-invasive monitoring of SD would allow early intervention and improve outcome in SD-related neurological disorders. Copyright © 2016 IBRO. All rights reserved.

  9. Non-invasive diagnosis of advanced fibrosis and cirrhosis.

    PubMed

    Sharma, Suraj; Khalili, Korosh; Nguyen, Geoffrey Christopher

    2014-12-07

    Liver cirrhosis is a common and growing public health problem globally. The diagnosis of cirrhosis portends an increased risk of morbidity and mortality. Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis. However, despite its universal use, liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks. In order to overcome the limitations of liver biopsy, a number of non-invasive techniques have been investigated for the assessment of cirrhosis. This review will focus on currently available non-invasive markers of cirrhosis. The evidence behind the use of these markers will be highlighted, along with an assessment of diagnostic accuracy and performance characteristics of each test. Non-invasive markers of cirrhosis can be radiologic or serum-based. Radiologic techniques based on ultrasound, magnetic resonance imaging and elastography have been used to assess liver fibrosis. Serum-based biomarkers of cirrhosis have also been developed. These are broadly classified into indirect and direct markers. Indirect biomarkers reflect liver function, which may decline with the onset of cirrhosis. Direct biomarkers, reflect extracellular matrix turnover, and include molecules involved in hepatic fibrogenesis. On the whole, radiologic and serum markers of fibrosis correlate well with biopsy scores, especially when excluding cirrhosis or excluding fibrosis. This feature is certainly clinically useful, and avoids liver biopsy in many cases.

  10. Infrared thermography: A non-invasive window into thermal physiology.

    PubMed

    Tattersall, Glenn J

    2016-12-01

    Infrared thermography is a non-invasive technique that measures mid to long-wave infrared radiation emanating from all objects and converts this to temperature. As an imaging technique, the value of modern infrared thermography is its ability to produce a digitized image or high speed video rendering a thermal map of the scene in false colour. Since temperature is an important environmental parameter influencing animal physiology and metabolic heat production an energetically expensive process, measuring temperature and energy exchange in animals is critical to understanding physiology, especially under field conditions. As a non-contact approach, infrared thermography provides a non-invasive complement to physiological data gathering. One caveat, however, is that only surface temperatures are measured, which guides much research to those thermal events occurring at the skin and insulating regions of the body. As an imaging technique, infrared thermal imaging is also subject to certain uncertainties that require physical modelling, which is typically done via built-in software approaches. Infrared thermal imaging has enabled different insights into the comparative physiology of phenomena ranging from thermogenesis, peripheral blood flow adjustments, evaporative cooling, and to respiratory physiology. In this review, I provide background and guidelines for the use of thermal imaging, primarily aimed at field physiologists and biologists interested in thermal biology. I also discuss some of the better known approaches and discoveries revealed from using thermal imaging with the objective of encouraging more quantitative assessment.

  11. 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

  12. Multimodality Cardiovascular Molecular Imaging Technology

    PubMed Central

    O’Donnell, Matthew; McVeigh, Elliot R.; Strauss, H. William; Tanaka, Atsushi; Bouma, Brett E.; Tearney, Guillermo J.; Guttman, Michael A.; Garcia, Ernest V.

    2010-01-01

    Cardiovascular molecular imaging is a new discipline that integrates scientific advances in both functional imaging and molecular probes to improve our understanding of the molecular basis of the cardiovascular system. These advances are driven by in vivo imaging of molecular processes in animals, usually small animals, and are rapidly moving toward clinical applications. Molecular imaging has the potential to revolutionize the diagnosis and treatment of cardiovascular disease. The 2 key components of all molecular imaging systems are the molecular contrast agents and the imaging system providing spatial and temporal localization of these agents within the body. They must deliver images with the appropriate sensitivity and specificity to drive clinical applications. As work in molecular contrast agents matures and highly sensitive and specific probes are developed, these systems will provide the imaging technologies required for translation into clinical tools. This is the promise of molecular medicine. PMID:20457794

  13. Photoacoustic molecular imaging

    NASA Astrophysics Data System (ADS)

    Kiser, William L., Jr.; Reinecke, Daniel; DeGrado, Timothy; Bhattacharyya, Sibaprasad; Kruger, Robert A.

    2007-02-01

    It is well documented that photoacoustic imaging has the capability to differentiate tissue based on the spectral characteristics of tissue in the optical regime. The imaging depth in tissue exceeds standard optical imaging techniques, and systems can be designed to achieve excellent spatial resolution. A natural extension of imaging the intrinsic optical contrast of tissue is to demonstrate the ability of photoacoustic imaging to detect contrast agents based on optically absorbing dyes that exhibit well defined absorption peaks in the infrared. The ultimate goal of this project is to implement molecular imaging, in which Herceptin TM, a monoclonal antibody that is used as a therapeutic agent in breast cancer patients that over express the HER2 gene, is labeled with an IR absorbing dye, and the resulting in vivo bio-distribution is mapped using multi-spectral, infrared stimulation and subsequent photoacoustic detection. To lay the groundwork for this goal and establish system sensitivity, images were collected in tissue mimicking phantoms to determine maximum detection depth and minimum detectable concentration of Indocyanine Green (ICG), a common IR absorbing dye, for a single angle photoacoustic acquisition. A breast mimicking phantom was constructed and spectra were also collected for hemoglobin and methanol. An imaging schema was developed that made it possible to separate the ICG from the other tissue mimicking components in a multiple component phantom. We present the results of these experiments and define the path forward for the detection of dye labeled Herceptin TM in cell cultures and mice models.

  14. Multispectral optoacoustic and MRI coregistration for molecular imaging of orthotopic model of human glioblastoma.

    PubMed

    Attia, Amalina Binte Ebrahim; Ho, Chris Jun Hui; Chandrasekharan, Prashant; Balasundaram, Ghayathri; Tay, Hui Chien; Burton, Neal C; Chuang, Kai-Hsiang; Ntziachristos, Vasilis; Olivo, Malini

    2016-07-01

    Multi-modality imaging methods are of great importance in oncologic studies for acquiring complementary information, enhancing the efficacy in tumor detection and characterization. We hereby demonstrate a hybrid non-invasive in vivo imaging approach of utilizing magnetic resonance imaging (MRI) and Multispectral Optoacoustic Tomography (MSOT) for molecular imaging of glucose uptake in an orthotopic glioblastoma in mouse. The molecular and functional information from MSOT can be overlaid on MRI anatomy via image coregistration to provide insights into probe uptake in the brain, which is verified by ex vivo fluorescence imaging and histological validation. In vivo MSOT and MRI imaging of an orthotopic glioma mouse model injected with IRDye800-2DG. Image coregistration between MSOT and MRI enables multifaceted (anatomical, functional, molecular) information from MSOT to be overlaid on MRI anatomy images to derive tumor physiological parameters such as perfusion, haemoglobin and oxygenation.

  15. [Non-invasive assessment of liver fibrosis].

    PubMed

    Cohen-Ezra, Oranit; Ben-Ari, Ziv

    2015-03-01

    Chronic liver diseases represent a major public health problem, accounting for significant morbidity and mortality worldwide. Prognosis and management of chronic liver diseases depend on the amount of liver fibrosis. Liver biopsy has long remained the gold standard for assessment of liver fibrosis. Liver biopsy is an invasive procedure with associated morbidity, it is rarely the cause for mortality, and has a few limitations. During the past two decades, in an attempt to overcome the limitations of liver biopsy, non-invasive methods for the evaluation of liver fibrosis have been developed, mainly in the field of viral hepatitis. This review will focus on different methods available for non-invasive evaluation of liver fibrosis including a biological approach which quantifies serum levels of biomarkers of fibrosis and physical techniques which measure liver stiffness by transient elastography, ultrasound or magnetic resonance based elastography, their accuracy, advantages and disadvantages.

  16. Ultrasonic non invasive techniques for microbiological instrumentation

    NASA Astrophysics Data System (ADS)

    Elvira, L.; Sierra, C.; Galán, B.; Resa, P.

    2010-01-01

    Non invasive techniques based on ultrasounds have advantageous features to study, characterize and monitor microbiological and enzymatic reactions. These processes may change the sound speed, viscosity or particle distribution size of the medium where they take place, which makes possible their analysis using ultrasonic techniques. In this work, two different systems for the analysis of microbiological liquid media based on ultrasounds are presented. In first place, an industrial application based on an ultrasonic monitoring technique for microbiological growth detection in milk is shown. Such a system may improve the quality control strategies in food production factories, being able to decrease the time required to detect possible contaminations in packed products. Secondly, a study about the growing of the Escherichia coli DH5 α in different conditions is presented. It is shown that the use of ultrasonic non invasive characterization techniques in combination with other conventional measurements like optical density provides complementary information about the metabolism of these bacteria.

  17. Non-invasive biomarkers in pancreatic cancer diagnosis: what we need versus what we have

    PubMed Central

    Bujanda, Luis

    2016-01-01

    Pancreatic cancer (PC) is probably the most lethal tumor being forecast as the second most fatal cancer by 2020 in developed countries. Only the earliest forms of the disease are a curable disease but it has to be diagnosed before symptoms starts. Detection at curable phase demands screening intervention for early detection and differential diagnosis. Unfortunately, no successful strategy or image technique has been concluded as effective approach and currently non-invasive biomarkers are the hope. Multiple translational research studies have explored minimally or non-invasive biomarkers in biofluids-blood, urine, stool, saliva or pancreatic juice, but diagnostic performance has not been validated yet. Nowadays no biomarker, alone or in combination, has been superior to carbohydrate antigen 19-9 (CA19-9) in sensitivity and specificity. Although the number of novel biomarkers for early diagnosis of PC has been increasing during the last couple of years, no molecular signature is ready to be implemented in clinical routine. Under the uncertain future, miRNAs profiling and methylation status seem to be the most promising biomarkers. However, good results in larger validations are urgently needed before application. Industry efforts through biotech and pharmaceutical companies are urgently required to demonstrate accuracy and validate promising results from basic and translational results. PMID:27162784

  18. Non-invasive biomarkers in pancreatic cancer diagnosis: what we need versus what we have.

    PubMed

    Herreros-Villanueva, Marta; Bujanda, Luis

    2016-04-01

    Pancreatic cancer (PC) is probably the most lethal tumor being forecast as the second most fatal cancer by 2020 in developed countries. Only the earliest forms of the disease are a curable disease but it has to be diagnosed before symptoms starts. Detection at curable phase demands screening intervention for early detection and differential diagnosis. Unfortunately, no successful strategy or image technique has been concluded as effective approach and currently non-invasive biomarkers are the hope. Multiple translational research studies have explored minimally or non-invasive biomarkers in biofluids-blood, urine, stool, saliva or pancreatic juice, but diagnostic performance has not been validated yet. Nowadays no biomarker, alone or in combination, has been superior to carbohydrate antigen 19-9 (CA19-9) in sensitivity and specificity. Although the number of novel biomarkers for early diagnosis of PC has been increasing during the last couple of years, no molecular signature is ready to be implemented in clinical routine. Under the uncertain future, miRNAs profiling and methylation status seem to be the most promising biomarkers. However, good results in larger validations are urgently needed before application. Industry efforts through biotech and pharmaceutical companies are urgently required to demonstrate accuracy and validate promising results from basic and translational results.

  19. The Non-Invasive Measurement of Regional Cerebral Blood Flow

    PubMed Central

    Wilson, Edwin M.; Wills, Edward L.

    1977-01-01

    The non-invasive, repeatable measurement of bilateral, regional cerebral blood flow in man is achieved through the application of the 133xenon inhalation method. The clinical utility of the methodology is enhanced by integrating the method into a computer system which combines on-line data acquisition with rapid data analysis and display. The subsequent statistical analysis of the results from specific patient categories and normal populations is facilitated by a computerized data base coupled with the primary computer system. ImagesFig. 2

  20. Ultrahigh-speed non-invasive widefield angiography

    NASA Astrophysics Data System (ADS)

    Blatter, Cedric; Klein, Thomas; Grajciar, Branislav; Schmoll, Tilman; Wieser, Wolfgang; Andre, Raphael; Huber, Robert; Leitgeb, Rainer A.

    2012-07-01

    Retinal and choroidal vascular imaging is an important diagnostic benefit for ocular diseases such as age-related macular degeneration. The current gold standard for vessel visualization is fluorescence angiography. We present a potential non-invasive alternative to image blood vessels based on functional Fourier domain optical coherence tomography (OCT). For OCT to compete with the field of view and resolution of angiography while maintaining motion artifacts to a minimum, ultrahigh-speed imaging has to be introduced. We employ Fourier domain mode locking swept source technology that offers high quality imaging at an A-scan rate of up to 1.68 MHz. We present retinal angiogram over ˜48 deg acquired in a few seconds in a single recording without the need of image stitching. OCT at 1060 nm allows for high penetration in the choroid and efficient separate characterization of the retinal and choroidal vascularization.

  1. Novel non invasive diagnostic strategies in bladder cancer

    PubMed Central

    TRUTA, ANAMARIA; POPON, TUDOR ADRIAN HODOR; SARACI, GEORGE; GHERVAN, LIVIU; POP, IOAN VICTOR

    2016-01-01

    Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, −145, −222, −210, −10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population. PMID:27152066

  2. Novel non invasive diagnostic strategies in bladder cancer.

    PubMed

    Truta, Anamaria; Popon, Tudor Adrian Hodor; Saraci, George; Ghervan, Liviu; Pop, Ioan Victor

    2016-01-01

    Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, -145, -222, -210, -10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population.

  3. Using a non-invasive technique in nutrition: synchrotron radiation infrared microspectroscopy spectroscopic characterization of oil seeds treated with different processing conditions on molecular spectral factors influencing nutrient delivery.

    PubMed

    Zhang, Xuewei; Yu, Peiqiang

    2014-07-02

    Non-invasive techniques are a key to study nutrition and structure interaction. Fourier transform infrared microspectroscopy coupled with a synchrotron radiation source (SR-IMS) is a rapid, non-invasive, and non-destructive bioanalytical technique. To understand internal structure changes in relation to nutrient availability in oil seed processing is vital to find optimal processing conditions. The objective of this study was to use a synchrotron-based bioanalytical technique SR-IMS as a non-invasive and non-destructive tool to study the effects of heat-processing methods and oil seed canola type on modeled protein structure based on spectral data within intact tissue that were randomly selected and quantify the relationship between the modeled protein structure and protein nutrient supply to ruminants. The results showed that the moisture heat-related processing significantly changed (p<0.05) modeled protein structures compared to the raw canola (control) and those processing by dry heating. The moisture heating increased (p<0.05) spectral intensities of amide I, amide II, α-helices, and β-sheets but decreased (p<0.05) the ratio of modeled α-helices to β-sheet spectral intensity. There was no difference (p>0.05) in the protein spectral profile between the raw and dry-heated canola tissue and between yellow- and brown-type canola tissue. The results indicated that different heat processing methods have different impacts on the protein inherent structure. The protein intrinsic structure in canola seed tissue was more sensitive and more response to the moisture heating in comparison to the dry heating. These changes are expected to be related to the nutritive value. However, the current study is based on limited samples, and more large-scale studies are needed to confirm our findings.

  4. 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.

  5. 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.

  6. Nanoparticles for molecular imaging.

    PubMed

    Sheng, Yang; Liao, Lun De; Thakor, Nitish V; Tan, Mei Chee

    2014-10-01

    Imaging techniques have been instrumental in the visualization of fundamental biological processes, identification and diagnosis of diseased states and the development of structure-function relationships at the cellular, tissue and anatomical levels. Together with the advancements made in imaging techniques, complementary chemical compounds, also known as imaging probes or contrast agents, are developed to improve the visibility of the image by enhancing sensitivity, and for the identification and quantitation of specific molecular species or structures. Extensive studies have been conducted to explore the use of inorganic nanoparticles which exhibit magnetic and optical properties unique to the nano regime so as to enhance the signals sensitivity for magnetic resonance and fluorescent imaging. These physical properties are tailored by controlling the size, shape and surface properties of nanoparticles. In addition, surface modification of nanoparticles is often required to improve its stability, compatibility and functionality. Surfactants, surface-active agents, have been used to engineer the surface characteristics of nanoparticles to improved particle stability and functionality. Surfactants enhance nanoparticle stability through the reduction of surface energy, and by acting as a barrier to agglomeration through either steric hindrance or repulsive electrostatic forces. Coupling of nanoparticles with biomolecules such as antibodies or tumor targeting peptides are enabled by the presence of functional groups (e.g., carboxyl or amine groups) on surfactants. This paper provides an overview of the chemistry underlying the synthesis and surface modification of nanomaterials together with a discussion on how the physical properties (e.g., magnetic, absorption and luminescent) can be controlled. The applications of these nanoparticles for magnetic resonance, fluorescent and photoacoustic imaging techniques that do not rely on ionizing radiation are also covered in

  7. Non invasive in vivo investigation of hepatobiliary structure and function in STII medaka (Oryzias latipes): methodology and applications

    PubMed Central

    Hardman, Ron C; Kullman, Seth W; Hinton, David E

    2008-01-01

    Background A novel transparent stock of medaka (Oryzias latipes; STII), recessive for all pigments found in chromatophores, permits transcutaneous imaging of internal organs and tissues in living individuals. Findings presented describe the development of methodologies for non invasive in vivo investigation in STII medaka, and the successful application of these methodologies to in vivo study of hepatobiliary structure, function, and xenobiotic response, in both 2 and 3 dimensions. Results Using brightfield, and widefield and confocal fluorescence microscopy, coupled with the in vivo application of fluorescent probes, structural and functional features of the hepatobiliary system, and xenobiotic induced toxicity, were imaged at the cellular level, with high resolution (< 1 μm), in living individuals. The findings presented demonstrate; (1) phenotypic response to xenobiotic exposure can be investigated/imaged in vivo with high resolution (< 1 μm), (2) hepatobiliary transport of solutes from blood to bile can be qualitatively and quantitatively studied/imaged in vivo, (3) hepatobiliary architecture in this lower vertebrate liver can be studied in 3 dimensions, and (4) non invasive in vivo imaging/description of hepatobiliary development in this model can be investigated. Conclusion The non-invasive in vivo methodologies described are a unique means by which to investigate biological structure, function and xenobiotic response with high resolution in STII medaka. In vivo methodologies also provide the future opportunity to integrate molecular mechanisms (e.g., genomic, proteomic) of disease and toxicity with phenotypic changes at the cellular and system levels of biological organization. While our focus has been the hepatobiliary system, other organ systems are equally amenable to in vivo study, and we consider the potential for discovery, within the context of in vivo investigation in STII medaka, as significant. PMID:18838008

  8. A review on the non-invasive evaluation of skeletal muscle oxygenation

    NASA Astrophysics Data System (ADS)

    Halim, A. A. A.; Laili, M. H.; Aziz, N. A.; Laili, A. R.; Salikin, M. S.; Rusop, M.

    2016-07-01

    The aim of this review is to conduct a feasibility study of non-invasive evaluation in skeletal muscle oxygenation. This non-invasive evaluation could extract many information using a safe non-invasive method regarding to the oxygenation and microcirculation status in human blood muscle. This brief review highlights the progress of the application of NIRS to evaluate skeletal muscle oxygenation in various activity of human nature from the historical point of view to the present advancement. Since the discovery of non-invasive optical method during 1992, there are many non-invasive techniques uses optical properties on human subject such as near infrared spectroscopy NIRS, optical topography, functional near infrared spectroscopy fNIRS and imaging fNIRI. Furthermore, in this paper we discuss the light absorption potential (LAP) towards chromophores content inside human muscle. Modified beer lambert law was studied in order to build a better understanding toward LAP between chromophores under tissue multilayers in human muscle. This paper will describe the NIRS principle and the basis for its proposed used in skeletal muscle oxygenation. This will cover the advantages and limitation of such application. Thus, these non-invasive techniques could open other possibilities to study muscle performance diagnosis.

  9. 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.

  10. Non-invasive methods for embryo selection

    PubMed Central

    Sallam, HN; Sallam, NH; Sallam, SH

    2016-01-01

    Abstract With the widespread use of assisted reproduction, a simple and practical method for embryo selection is needed to optimize the chances of pregnancy while diminishing the incidence of multiple pregnancy and its accompanying problems. Many non-invasive methods for embryo selection have been proposed and some are more promising than others. This review summarizes these methods and attempts to evaluate them in the light of the best currently available evidence and to find out whether any of them is ripe for replacing or supplementing the time-honored method of morphological assessment. PMID:27909565

  11. Non-invasive diagnosis of liver fibrosis and cirrhosis.

    PubMed

    Lurie, Yoav; Webb, Muriel; Cytter-Kuint, Ruth; Shteingart, Shimon; Lederkremer, Gerardo Z

    2015-11-07

    The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.

  12. Non-invasive assessment of cardiac output in children.

    PubMed Central

    Richardson, J R; Ferguson, J; Hiscox, J; Rawles, J

    1998-01-01

    BACKGROUND: Stroke distance, the systolic velocity integral of aortic blood flow, is a linear analogue of stroke volume; its product with heart rate is minute distance, analogous to cardiac output. OBJECTIVE: To investigate the feasibility of assessing cardiac output in children with a simple non-invasive Doppler ultrasound technique, and to determine the normal range of values. METHODS: Peak aortic blood velocity, stroke distance, and minute distance were measured through the suprasternal window in 166 children (mean age 9.6 years, range 2-14) using a portable non-imaging Doppler ultrasound instrument. RESULTS: The technique was well tolerated by all the children participating. Mean peak aortic blood velocity was 138 cm/s and was independent of age. Mean stroke distance was 31.8 cm and showed a small but significant increase with age; mean minute distance was 2490 cm and fell with age, as did heart rate. CONCLUSIONS: Suprasternal Doppler ultrasound measurement of stroke distance is a convenient, well tolerated, non-invasive technique for the assessment of cardiac output in children. The normal range of values during childhood has been established. The technique has great potential for assessing hypovolaemia in children. Images p307-a PMID:9785155

  13. Non-invasive diagnosis of liver fibrosis and cirrhosis

    PubMed Central

    Lurie, Yoav; Webb, Muriel; Cytter-Kuint, Ruth; Shteingart, Shimon; Lederkremer, Gerardo Z

    2015-01-01

    The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this “gold-standard” is imperfect; even according to its proponents, it is only “the best” among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future. PMID:26556987

  14. In vivo non-invasive multiphoton tomography of human skin

    NASA Astrophysics Data System (ADS)

    König, Karsten; Riemann, Iris; Ehlers, Alexander; Le Harzic, Ronan

    2005-10-01

    High resolution non-invasive 3D imaging devices are required to detect pathogenic microorganisms such as Anthrax spores, bacteria, viruses, fungi and chemical agents entering biological tissues such as the epidermis. Due to the low light penetration depth and the biodamage potential, ultraviolet light sources can not be employed to realize intratissue imaging of bio- and chemohazards. We report on the novel near infrared laser technology multiphoton tomography and the high resolution 4D imaging tool DermaInspect for non-invasive detection of intratissue agents and their influence on cellular metabolism based on multiphoton autofluorescence imaging (MAI) and second harmonic generation (SHG). Femtosecond laser pulses in the spectral range of 750 nm to 850 nm have been used to image in vivo human skin with subcellular spatial and picosecond temporal resolution. The non-linear induced autofluorescence of both, skin tissues and microorganisms, originates mainly from naturally endogenous fluorophores/protein structures like NAD(P)H, flavins, keratin, collagen, elastin, porphyrins and melanin. Bacteria emit in the blue/green spectral range due to NAD(P)H and flavoproteins and, in certain cases, in the red spectral range due to the biosynthesis of Zn-porphyrins, coproporphyrin and protoporphyrin. Collagen and exogenous non-centrosymmetric molecules can be detected by SHG signals. The system DermaInspect consists of a wavelength-tunable compact 80/90 MHz Ti:sapphire laser, a scan module with galvo scan mirrors, piezo-driven objective, fast photon detector and time-resolved single photon counting unit. It can be used to perform optical sectioning and 3D autofluorescence lifetime imaging (τ-mapping) with 1 μm spatial resolution and 270 ps temporal resolution. The parameter fluorescence lifetime depends on the type of fluorophore and its microenvironment and can be used to distinguish bio- and chemohazards from cellular background and to gain information for pathogen

  15. Molecular imaging applications for immunology.

    PubMed

    Hildebrandt, Isabel Junie; Gambhir, Sanjiv Sam

    2004-05-01

    The use of multimodality molecular imaging has recently facilitated the study of molecular and cellular events in living subjects in a noninvasive and repetitive manner to improve the diagnostic capability of traditional assays. The noninvasive imaging modalities utilized for both small animal and human imaging include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT). Techniques specific to small-animal imaging include bioluminescent imaging (BIm) and fluorescent imaging (FIm). Molecular imaging permits the study of events within cells, the examination of cell trafficking patterns that relate to inflammatory diseases and metastases, and the ability to rapidly screen new drug treatments for distribution and effectiveness. In this paper, we will review the current field of molecular imaging assays (especially those utilizing PET and BIm modalities) and examine how they might impact animal models and human disease in the field of clinical immunology.

  16. Hybrid CARS for Non-Invasive Blood Glucose Monitoring

    NASA Astrophysics Data System (ADS)

    Wang, Xi; Pestov, Dmitry; Zhang, Aihua; Murawski, Robert; Sokolov, Alexei; Welch, George; Laane, Jaan; Scully, Marlan

    2007-10-01

    We develop a spectroscopy technique that combines the advantages of both the frequency-resolved coherent anti-Stokes Raman scattering (CARS) and the time-resolved CARS. We use broadband preparation pulses to get an instantaneous coherent excitation of multiplex molecular vibration levels and subsequent optically shaped time-delayed narrowband probing pulse to detect these vibrations. This technique can suppress the nonresonant background and retrieve the molecular fingerprint signal efficiently and rapidly. We employ this technique to glucose detection, the final goal of which is accurate, non-invasive (i.e. painless) and continuous monitoring of blood glucose concentration in the Diabetes diagnosis to replace the current glucose measurement process, which requires painful fingerpricks and therefore cannot be performed more than a few times a day. We have gotten the CARS spectra of glucose aqueous solution down to 2 mM.

  17. Non-invasive primate head restraint using thermoplastic masks.

    PubMed

    Drucker, Caroline B; Carlson, Monica L; Toda, Koji; DeWind, Nicholas K; Platt, Michael L

    2015-09-30

    The success of many neuroscientific studies depends upon adequate head fixation of awake, behaving animals. Typically, this is achieved by surgically affixing a head-restraint prosthesis to the skull. Here we report the use of thermoplastic masks to non-invasively restrain monkeys' heads. Mesh thermoplastic sheets become pliable when heated and can then be molded to an individual monkey's head. After cooling, the custom mask retains this shape indefinitely for day-to-day use. We successfully trained rhesus macaques (Macaca mulatta) to perform cognitive tasks while wearing thermoplastic masks. Using these masks, we achieved a level of head stability sufficient for high-resolution eye-tracking and intracranial electrophysiology. Compared with traditional head-posts, we find that thermoplastic masks perform at least as well during infrared eye-tracking and single-neuron recordings, allow for clearer magnetic resonance image acquisition, enable freer placement of a transcranial magnetic stimulation coil, and impose lower financial and time costs on the lab. We conclude that thermoplastic masks are a viable non-invasive form of primate head restraint that enable a wide range of neuroscientific experiments. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Non-invasive primate head restraint using thermoplastic masks

    PubMed Central

    Drucker, Caroline B.; Carlson, Monica L.; Toda, Koji; DeWind, Nicholas K.; Platt, Michael L.

    2015-01-01

    Background The success of many neuroscientific studies depends upon adequate head fixation of awake, behaving animals. Typically, this is achieved by surgically affixing a head-restraint prosthesis to the skull. New Method Here we report the use of thermoplastic masks to non-invasively restrain monkeys’ heads. Mesh thermoplastic sheets become pliable when heated and can then be molded to an individual monkey’s head. After cooling, the custom mask retains this shape indefinitely for day-to-day use. Results We successfully trained rhesus macaques (Macaca mulatta) to perform cognitive tasks while wearing thermoplastic masks. Using these masks, we achieved a level of head stability sufficient for high-resolution eye-tracking and intracranial electrophysiology. Comparison with Existing Method Compared with traditional head-posts, we find that thermoplastic masks perform at least as well during infrared eye-tracking and single-neuron recordings, allow for clearer magnetic resonance image acquisition, enable freer placement of a transcranial magnetic stimulation coil, and impose lower financial and time costs on the lab. Conclusions We conclude that thermoplastic masks are a viable non-invasive form of primate head restraint that enable a wide range of neuroscientific experiments. PMID:26112334

  19. Molecular Imaging of Breast Cancer: Role of RGD Peptides.

    PubMed

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2015-01-01

    Breast cancer is the leading cause of cancer deaths among women of all ages worldwide. With advances in molecular imaging procedures, it has been possible to detect breast cancer in its early stage, determine the extent of the disease to administer appropriate therapeutic protocol and also monitor the effects of treatment. By accurately characterizing the tumor properties and biological processes involved, molecular imaging can play a crucial role in minimizing the morbidity and mortality associated with breast cancer. The integrin αvβ3 plays an important role in breast cancer angiogenesis and is expressed on tumor endothelial cells as well as on some tumor cells. It is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic acid (RGD) tripeptide sequence and therefore RGD peptides can preferentially bind to integrin αvβ3. In this context, targeting tumor vasculature or tumor cells by RGD-based probes is a promising strategy for molecular imaging of breast cancer. Using RGD-based probes, several preclinical studies have employed different imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound and optical imaging for visualization of integrin αvβ3 expression in breast cancer models. Limited clinical trials using (18)F-labeled RGD peptides have also been initiated for non-invasive detection and staging of breast cancer. Herein, we provide a comprehensive overview of the latest advances in molecular imaging of breast cancer using RGD peptide-based probes and discuss the challenges and opportunities for advancement of the field. The reported strategies for molecular imaging of breast cancer using RGD peptide-based probes holds promise for making clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in improved quality of life for breast cancer patients.

  20. Molecular imaging in Alzheimer's disease.

    PubMed

    Lascola, Christopher

    2005-11-01

    Molecular imaging represents a new term for a long-standing quest to image cellular and molecular processes in vivo. The development of a successful molecular imaging approach starts with a well-defined diagnostic question best answered using in vivo imaging. A selective target for a particular disease state is then identified and a biocompatible probe selective for that target is developed. Many of the challenges of finding selective disease targets and probes that bind selectively to those targets in vivo are evident in the 25-year history of molecular imaging in Alzheimer's disease. This article provides a brief overview of molecular imaging in Alzheimer's disease and its potential for early diagnosis and treatment development.

  1. Non-invasive neuroimaging using near-infrared light

    NASA Technical Reports Server (NTRS)

    Strangman, Gary; Boas, David A.; Sutton, Jeffrey P.

    2002-01-01

    This article reviews diffuse optical brain imaging, a technique that employs near-infrared light to non-invasively probe the brain for changes in parameters relating to brain function. We describe the general methodology, including types of measurements and instrumentation (including the tradeoffs inherent in the various instrument components), and the basic theory required to interpret the recorded data. A brief review of diffuse optical applications is included, with an emphasis on research that has been done with psychiatric populations. Finally, we discuss some practical issues and limitations that are relevant when conducting diffuse optical experiments. We find that, while diffuse optics can provide substantial advantages to the psychiatric researcher relative to the alternative brain imaging methods, the method remains substantially underutilized in this field.

  2. Non-invasive neuroimaging using near-infrared light

    NASA Technical Reports Server (NTRS)

    Strangman, Gary; Boas, David A.; Sutton, Jeffrey P.

    2002-01-01

    This article reviews diffuse optical brain imaging, a technique that employs near-infrared light to non-invasively probe the brain for changes in parameters relating to brain function. We describe the general methodology, including types of measurements and instrumentation (including the tradeoffs inherent in the various instrument components), and the basic theory required to interpret the recorded data. A brief review of diffuse optical applications is included, with an emphasis on research that has been done with psychiatric populations. Finally, we discuss some practical issues and limitations that are relevant when conducting diffuse optical experiments. We find that, while diffuse optics can provide substantial advantages to the psychiatric researcher relative to the alternative brain imaging methods, the method remains substantially underutilized in this field.

  3. Molecular imaging with engineered physiology

    PubMed Central

    Desai, Mitul; Slusarczyk, Adrian L.; Chapin, Ashley; Barch, Mariya; Jasanoff, Alan

    2016-01-01

    In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms. PMID:27910951

  4. Molecular imaging with engineered physiology.

    PubMed

    Desai, Mitul; Slusarczyk, Adrian L; Chapin, Ashley; Barch, Mariya; Jasanoff, Alan

    2016-12-02

    In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms.

  5. The value of non-invasive ventilation.

    PubMed

    Hull, Jeremy

    2014-11-01

    Non-invasive ventilation (NIV) use has increased markedly over the last 10 years. Children being treated with NIV are now a common sight in most paediatric intensive care units and high dependency units and nearly all tertiary respiratory units will look after a cohort of children who use NIV at home. Although the published evidence base for use of NIV in acute and chronic respiratory failure is relatively weak, it is now very unlikely that there will be any more randomised controlled trials of this intervention. Effectiveness of NIV will need to be evaluated on each child as it used. It is important to define the purpose of using NIV in each child, and then determine whether it is effective. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. MOLECULAR IMAGING OF THE INITIAL INFLAMMATORY RESPONSE IN ATHEROSCLEROSIS: IMPLICATIONS FOR EARLY DETECTION OF DISEASE

    PubMed Central

    Kaufmann, Beat A.; Carr, Chad L.; Belcik, J. Todd; Xie, Aris; Yue, Qi; Chadderdon, Scott; Caplan, Evan S.; Khangura, Jaspreet; Bullens, Sherry; Bunting, Stuart; Lindner, Jonathan R.

    2009-01-01

    Background We hypothesized that molecular imaging of endothelial cell adhesion molecule expression could non-invasively evaluate pre-lesion pro-atherogenic phenotype. Methods Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model of atherosclerosis. At 10, 20, and 40 weeks of age, ultrasound molecular imaging of the proximal thoracic aorta was performed with contrast agents targeted to P-selectin and VCAM-1. Atherosclerotic lesion severity and content were assessed by ultra-high frequency ultrasound, histology, and immunohistochemistry. Results In wild-type mice at all ages, there was neither aortic thickening nor targeted tracer signal enhancement. In DKO mice, lesions progressed from sparse mild intimal thickening at 10 weeks to widespread severe lesions with luminal encroachment at 40 weeks. Molecular imaging for P-selectin and VCAM-1 demonstrated selective signal enhancement (p<0.01 vs. non-targeted agent) at all ages for DKO mice. P-selectin and VCAM-1 signal in DKO mice were greater by 3-fold at 10 wks, 4–6-fold at 20 wks, and 9–10-fold at 40 weeks compared to wild-type mice. En face microscopy demonstrated preferential attachment of targeted microbubbles to regions of lesion formation. Conclusions Non-invasive ultrasound molecular imaging of endothelial activation can detect lesion-prone vascular phenotype before the appearance of obstructive atherosclerotic lesions. PMID:19834105

  7. Magnetic Resonance in the Era of Molecular Imaging of Cancer

    PubMed Central

    Gore, John C.; Manning, H. Charles; Quarles, C. Chad; Waddell, Kevin W.; Yankeelov, Thomas E.

    2011-01-01

    MRI has played an important role in the diagnosis and management of cancer since it was first developed, but other modalities also continue to advance and provide complementary information on the status of tumors. In the future there will be a major continuing role for non-invasive imaging in order to obtain information on the location and extent of cancer, as well as assessments of tissue characteristics that can monitor and predict treatment response and guide patient management. Developments are currently being undertaken that aim to provide improved imaging methods for the detection and evaluation of tumors, for identifying important characteristics of tumors such as the expression levels of cell surface receptors that may dictate what types of therapy will be effective, and for evaluating their response to treatments. Molecular imaging techniques based mainly on radionuclide imaging can depict numerous, specific, cellular and molecular markers of disease and have unique potential to address important clinical and research challenges. In this review we consider what continuing and evolving roles will be played by MRI in this era of molecular imaging. We discuss some of the challenges for MRI of detecting imaging agents that report on molecular events, but highlight also the ability of MRI to assess other features such as cell density, blood flow and metabolism which are not specific hallmarks of cancer but which reflect molecular changes. We discuss the future role of MRI in cancer and describe the use of selected quantitative imaging techniques for characterizing tumors that can be translated to clinical applications, particularly in the context of evaluating novel treatments. PMID:21524870

  8. Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging

    PubMed Central

    Heidt, Timo; Ehrismann, Simon; Hövener, Jan-Bernd; Neudorfer, Irene; Hilgendorf, Ingo; Reisert, Marco; Hagemeyer, Christoph E.; Zirlik, Andreas; Reinöhl, Jochen; Bode, Christoph; Peter, Karlheinz; von Elverfeldt, Dominik; von zur Muhlen, Constantin

    2016-01-01

    Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism. PMID:27138487

  9. Non-invasive diagnosis of alcoholic liver disease

    PubMed Central

    Mueller, Sebastian; Seitz, Helmut Karl; Rausch, Vanessa

    2014-01-01

    Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. PMID:25356026

  10. 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

  11. Long-term non-invasive ventilation in children.

    PubMed

    Amaddeo, Alessandro; Frapin, Annick; Fauroux, Brigitte

    2016-12-01

    Use of long-term non-invasive ventilation is increasing exponentially worldwide in children of all ages. The treatment entails delivery of ventilatory assistance through a non-invasive interface. Indications for use of non-invasive ventilation include conditions that affect normal respiratory balance (eg, those associated with dysfunction of the central drive or respiratory muscles) and disorders characterised by an increase in respiratory load (eg, obstructive airway or lung diseases). The type of non-invasive ventilation used depends on the pathophysiological features of the respiratory failure. For example, non-invasive ventilation will need to either replace central drive if the disorder is characterised by an abnormal central drive or substitute for the respiratory muscles if the condition is associated with respiratory muscle weakness. Non-invasive ventilation might also need to unload the respiratory muscles in case of an increase in respiratory load, as seen in upper airway obstruction and some lung diseases. Technical aspects are also important when choosing non-invasive ventilation-eg, appropriate interface and device. The great heterogeneity of disorders, age ranges of affected children, prognoses, and outcomes of patients needing long-term non-invasive ventilation underline the need for management by skilled multidisciplinary centres with technical competence in paediatric non-invasive ventilation and expertise in sleep studies and therapeutic education.

  12. Implementation of non-invasive brain physiological monitoring concepts.

    PubMed

    Ragauskas, Arminas; Daubaris, Gediminas; Ragaisis, Vytautas; Petkus, Vytautas

    2003-10-01

    The paper presents innovative methods and technology for non-invasive intracranial hemodynamics monitoring based on the measurement of brain parenchyma acoustic properties. The clinical investigation of new technology shows the similarity between the invasively recorded intracranial pressure (ICP) and non-invasively recorded intracranial blood volume (IBV) pulse waves, slow waves and slow trends under intensive care unit (ICU) conditions. Also, the applicability of the non-invasive IBV slow wave monitoring technique for cerebrovascular autoregulation non-invasive long-term monitoring is demonstrated by theoretical and experimental studies.

  13. Biomechanics of subcellular structures by non-invasive Brillouin microscopy

    NASA Astrophysics Data System (ADS)

    Antonacci, Giuseppe; Braakman, Sietse

    2016-11-01

    Cellular biomechanics play a pivotal role in the pathophysiology of several diseases. Unfortunately, current methods to measure biomechanical properties are invasive and mostly limited to the surface of a cell. As a result, the mechanical behaviour of subcellular structures and organelles remains poorly characterised. Here, we show three-dimensional biomechanical images of single cells obtained with non-invasive, non-destructive Brillouin microscopy with an unprecedented spatial resolution. Our results quantify the longitudinal elastic modulus of subcellular structures. In particular, we found the nucleoli to be stiffer than both the nuclear envelope (p < 0.0001) and the surrounding cytoplasm (p < 0.0001). Moreover, we demonstrate the mechanical response of cells to Latrunculin-A, a drug that reduces cell stiffness by preventing cytoskeletal assembly. Our technique can therefore generate valuable insights into cellular biomechanics and its role in pathophysiology.

  14. Biomechanics of subcellular structures by non-invasive Brillouin microscopy

    PubMed Central

    Antonacci, Giuseppe; Braakman, Sietse

    2016-01-01

    Cellular biomechanics play a pivotal role in the pathophysiology of several diseases. Unfortunately, current methods to measure biomechanical properties are invasive and mostly limited to the surface of a cell. As a result, the mechanical behaviour of subcellular structures and organelles remains poorly characterised. Here, we show three-dimensional biomechanical images of single cells obtained with non-invasive, non-destructive Brillouin microscopy with an unprecedented spatial resolution. Our results quantify the longitudinal elastic modulus of subcellular structures. In particular, we found the nucleoli to be stiffer than both the nuclear envelope (p < 0.0001) and the surrounding cytoplasm (p < 0.0001). Moreover, we demonstrate the mechanical response of cells to Latrunculin-A, a drug that reduces cell stiffness by preventing cytoskeletal assembly. Our technique can therefore generate valuable insights into cellular biomechanics and its role in pathophysiology. PMID:27845411

  15. Non-invasive exploration in an environmentally sensitive world

    USGS Publications Warehouse

    Livo, K.E.; Knepper, D.H.

    2004-01-01

    Modern remote sensing provides a means for locating and characterizing exposed mineralized systems in many parts of the world. These capabilities are non-invasive and help target specific areas for more detailed exploration. An example of how remote sensing technology can be used is evident from a study of the Questa Mining District, New Mexico. Analysis of low spectral resolution data from the Landsat Thematic Mapper satellite system clearly shows the regional distribution of two broad mineral groups often associated with mineralized systems: clay-carbonate-sulfate and iron oxides-iron hydroxides. Analysis of high spectral resolution data from the Airborne Visible and Infrared Imaging System (AVIRIS) shows the occurrence and distribution of many individual mineral species that characterize the pattern of hydrothermally altered rocks in the district.

  16. Systematic review: non-invasive methods of fibrosis analysis in chronic hepatitis C.

    PubMed

    Smith, J O; Sterling, R K

    2009-09-15

    Accurate determination of the presence and degree of liver fibrosis is essential for prognosis and for planning treatment of patients with chronic hepatitis C virus (HCV). Non-invasive methods of assessing fibrosis have been developed to reduce the need for biopsy. To perform a review of these non-invasive measures and their ability to replace biopsy for assessing hepatic fibrosis in patients with chronic HCV. A systematic review of PUBMED and EMBASE was performed through 2008 using the following search terms: HCV, liver, elastography, hepatitis, Fibroscan, SPECT, noninvasive liver fibrosis, ultrasonography, Doppler, MRI, Fibrotest, Fibrosure, Actitest, APRI, Forns and breath tests, alone or in combination. We identified 151 studies: 87 using biochemical, 57 imaging and seven breath tests either alone or in combination. Great strides are being made in the development of accurate non-invasive methods for determination of fibrosis. Although no single non-invasive test or model developed to date can match that information obtained from actual histology (i.e. inflammation, fibrosis, steatosis), combinations of two modalities of non-invasive methods can reliably differentiate between minimal and significant fibrosis, and thereby avoid liver biopsy in a significant percentage of patients.

  17. Transcriptome Analysis Showed a Differential Signature between Invasive and Non-invasive Corticotrophinomas

    PubMed Central

    de Araújo, Leonardo Jose Tadeu; Lerario, Antonio Marcondes; de Castro, Margaret; Martins, Clarissa Silva; Bronstein, Marcello Delano; Machado, Marcio Carlos; Trarbach, Ericka Barbosa; Villares Fragoso, Maria Candida Barisson

    2017-01-01

    ACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushing’s disease (CD)] is the most common cause of endogenous Cushing’s syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (≈80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, ≥10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also

  18. Transcriptome Analysis Showed a Differential Signature between Invasive and Non-invasive Corticotrophinomas.

    PubMed

    de Araújo, Leonardo Jose Tadeu; Lerario, Antonio Marcondes; de Castro, Margaret; Martins, Clarissa Silva; Bronstein, Marcello Delano; Machado, Marcio Carlos; Trarbach, Ericka Barbosa; Villares Fragoso, Maria Candida Barisson

    2017-01-01

    ACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushing's disease (CD)] is the most common cause of endogenous Cushing's syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (≈80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, ≥10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also

  19. In vivo carbon nanotube-enhanced non-invasive photoacoustic mapping of the sentinel lymph node

    NASA Astrophysics Data System (ADS)

    Pramanik, Manojit; Song, Kwang Hyun; Swierczewska, Magdalena; Green, Danielle; Sitharaman, Balaji; Wang, Lihong V.

    2009-06-01

    Sentinel lymph node biopsy (SLNB), a less invasive alternative to axillary lymph node dissection (ALND), has become the standard of care for patients with clinically node-negative breast cancer. In SLNB, lymphatic mapping with radio-labeled sulfur colloid and/or blue dye helps identify the sentinel lymph node (SLN), which is most likely to contain metastatic breast cancer. Even though SLNB, using both methylene blue and radioactive tracers, has a high identification rate, it still relies on an invasive surgical procedure, with associated morbidity. In this study, we have demonstrated a non-invasive single-walled carbon nanotube (SWNT)-enhanced photoacoustic (PA) identification of SLN in a rat model. We have successfully imaged the SLN in vivo by PA imaging (793 nm laser source, 5 MHz ultrasonic detector) with high contrast-to-noise ratio (=89) and good resolution (~500 µm). The SWNTs also show a wideband optical absorption, generating PA signals over an excitation wavelength range of 740-820 nm. Thus, by varying the incident light wavelength to the near infrared region, where biological tissues (hemoglobin, tissue pigments, lipids and water) show low light absorption, the imaging depth is maximized. In the future, functionalization of the SWNTs with targeting groups should allow the molecular imaging of breast cancer.

  20. Advances in multimodal molecular imaging.

    PubMed

    Auletta, Luigi; Gramanzini, Matteo; Gargiulo, Sara; Albanese, Sandra; Salvatore, Marco; Greco, Adelaide

    2017-03-01

    Preclinical molecular imaging is an emerging field. Improving the ability of scientists to study the molecular basis of human pathology in animals is of the utmost importance for future advances in all fields of human medicine. Moreover, the possibility of developing new imaging techniques or of implementing old ones adapted to the clinic is a significant area. Cardiology, neurology, immunology and oncology have all been studied with preclinical molecular imaging. The functional techniques of photoacoustic imaging (PAI), fluorescence molecular tomography (FMT), positron emission tomography (PET), and single photon emission computed tomography (SPECT) in association with each other or with the anatomic reference provided by computed tomography (CT) as well as with anatomic and functional information provided by magnetic resonance (MR) have all been proficiently applied to animal models of human disease. All the above-mentioned imaging techniques have shown their ability to explore the molecular mechanisms involved in animal models of disease. The clinical translatability of most of the techniques motivates the ongoing study of their possible fields of application. The ability to combine two or more techniques allows obtaining as much information as possible on the molecular processes involved in pathologies, reducing the number of animals necessary in each experiment. Merging molecular probes compatible with various imaging technique will further expand the capability to achieve the best results.

  1. Non-invasive coronary wave intensity analysis.

    PubMed

    Broyd, Christopher J; Rigo, Fausto; Davies, Justin

    2017-07-01

    Wave intensity analysis is calculated from simultaneously acquired measures of pressure and flow. Its mathematical computation produces a profile that provides quantitative information on the energy exchange driving blood flow acceleration and deceleration. Within the coronary circulation it has proven most useful in describing the wave that originates from the myocardium and that is responsible for driving the majority of coronary flow, labelled the backward decompression wave. Whilst this wave has demonstrated valuable insights into the pathogenic processes of a number of disease states, its measurement is hampered by its invasive necessity. However, recent work has used transthoracic echocardiography and an established measures of central aortic pressure to produce coronary flow velocity and pressure waveforms respectively. This has allowed a non-invasive measure of coronary wave intensity analysis, and in particular the backward decompression wave, to be calculated. It is anticipated that this will allow this tool to become more applicable and widespread, ultimately moving it from the research to the clinical domain.

  2. Introduction to the special issue on molecular imaging in radiation biology.

    PubMed

    Humm, John L; Dewhirst, Mark W; Bhujwalla, Zaver M

    2012-04-01

    Molecular imaging is an evolving science that is concerned with the development of novel imaging probes and biomarkers that can be used to non-invasively image molecular and cellular processes. This special issue approaches molecular imaging in the context of radiation research, focusing on biomarkers and imaging methods that provide measurable signals that can assist in the quantification of radiation-induced effects of living systems at the physical, chemical and biological levels. The potential to image molecular changes in response to a radiation insult opens new and exciting opportunities for a more profound understanding of radiation biology, with the possibility of translation of these techniques to radiotherapy practice. This special issue brings together 14 reviews dedicated to the use of molecular imaging in the field of radiation research. The initial three reviews are introductory overviews of the key molecular imaging modalities: magnetic resonance, nuclear and optical. This is followed by 11 reviews each focusing on a specialist area within the field of radiation research. These include: hypoxia and perfusion, tissue metabolism, normal tissue injury, cell death and viability, receptor targeting and nanotechnology, reporter genes, reactive oxygen species (ROS), and biological dosimetry. Over the preceding decade, molecular imaging brought significant new a