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Sample records for molecular imaging non-invasive

  1. 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

  2. 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.

  3. Monitoring molecular, functional and morphologic aspects of bone metastases using non-invasive imaging.

    PubMed

    Bauerle, Tobias; Komljenovic, Dorde; Semmler, Wolfhard

    2012-03-01

    Bone is among the most common locations of metastasis and therefore represents an important clinical target for diagnostic follow-up in cancer patients. In the pathogenesis of bone metastases, disseminated tumor cells proliferating in bone interact with the local microenvironment stimulating or inhibiting osteoclast and osteoblast activity. Non-invasive imaging methods monitor molecular, functional and morphologic changes in both compartments of these skeletal lesions - the bone and the soft tissue tumor compartment. In the bone compartment, morphologic information on skeletal destruction is assessed by computed tomography (CT) and radiography. Pathogenic processes of osteoclast and osteoblast activity, however, can be imaged using optical imaging, positron emission tomography (PET), single photon emission CT (SPECT) and skeletal scintigraphy. Accordingly, conventional magnetic resonance imaging (MRI) and CT as well as diffusion- weighted MRI and optical imaging are used to assess morphologic aspects on the macroscopic and cellular level of the soft tissue tumor compartment. Imaging methods such as PET, MR spectroscopy, dynamic contrast-enhanced techniques and vessel size imaging further elucidate on pathogenic processes in this compartment including information on metabolism and vascularization. By monitoring these aspects in bone lesions, new insights in the pathogenesis of skeletal metastases can be gained. In translation to the clinical situation, these novel methods for the monitoring of bone metastases might be applied in patients to improve follow-up of these lesions, in particular after therapeutic intervention. This review summarizes established and experimental imaging techniques for the monitoring of tumor and bone cell activity including molecular, functional and morphological aspects in bone metastases. PMID:22214500

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

    PubMed

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

    2015-10-01

    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

  5. Non-Invasive Molecular Imaging of Fibrosis Using a Collagen-Targeted Peptidomimetic of the Platelet Collagen Receptor Glycoprotein VI

    PubMed Central

    Loyau, Stéphane; Meulemans, Alain; Louedec, Liliane; Bantsimba-Malanda, Claudie; Hervatin, Florence; Marchal-Somme, Joëlle; Michel, Jean Baptiste; Le Guludec, Dominique; Billiald, Philippe; Jandrot-Perrus, Martine

    2009-01-01

    Background Fibrosis, which is characterized by the pathological accumulation of collagen, is recognized as an important feature of many chronic diseases, and as such, constitutes an enormous health burden. We need non-invasive specific methods for the early diagnosis and follow-up of fibrosis in various disorders. Collagen targeting molecules are therefore of interest for potential in vivo imaging of fibrosis. In this study, we developed a collagen-specific probe using a new approach that takes advantage of the inherent specificity of Glycoprotein VI (GPVI), the main platelet receptor for collagens I and III. Methodology/Principal Findings An anti-GPVI antibody that neutralizes collagen-binding was used to screen a bacterial random peptide library. A cyclic motif was identified, and the corresponding peptide (designated collagelin) was synthesized. Solid-phase binding assays and histochemical analysis showed that collagelin specifically bound to collagen (Kd 10−7 M) in vitro, and labelled collagen fibers ex vivo on sections of rat aorta and rat tail. Collagelin is therefore a new specific probe for collagen. The suitability of collagelin as an in vivo probe was tested in a rat model of healed myocardial infarctions (MI). Injecting Tc-99m-labelled collagelin and scintigraphic imaging showed that uptake of the probe occurred in the cardiac area of rats with MI, but not in controls. Post mortem autoradiography and histological analysis of heart sections showed that the labeled areas coincided with fibrosis. Scintigraphic molecular imaging with collagelin provides high resolution, and good contrast between the fibrotic scars and healthy tissues. The capacity of collagelin to image fibrosis in vivo was confirmed in a mouse model of lung fibrosis. Conclusion/Significance Collagelin is a new collagen-targeting agent which may be useful for non-invasive detection of fibrosis in a broad spectrum of diseases. PMID:19440310

  6. Non-Invasive Imaging of Vascular Inflammation

    PubMed Central

    Ammirati, Enrico; Moroni, Francesco; Pedrotti, Patrizia; Scotti, Isabella; Magnoni, Marco; Bozzolo, Enrica P.; Rimoldi, Ornella E.; Camici, Paolo G.

    2014-01-01

    In large-vessel vasculitides, inflammatory infiltrates may cause thickening of the involved arterial vessel wall leading to progressive stenosis and occlusion. Dilatation, aneurysm formation, and thrombosis may also ensue. Activated macrophages and T lymphocytes are fundamental elements in vascular inflammation. The amount and density of the inflammatory infiltrate is directly linked to local disease activity. Additionally, patients with autoimmune disorders have an increased cardiovascular (CV) risk compared with age-matched healthy individuals as a consequence of accelerated atherosclerosis. Molecular imaging techniques targeting activated macrophages, neovascularization, or increased cellular metabolic activity can represent effective means of non-invasive detection of vascular inflammation. In the present review, novel non-invasive imaging tools that have been successfully tested in humans will be presented. These include contrast-enhanced ultrasonography, which allows detection of neovessels within the wall of inflamed arteries; contrast-enhanced CV magnetic resonance that can detect increased thickness of the arterial wall, usually associated with edema, or mural enhancement using T2 and post-contrast T1-weighted sequences, respectively; and positron emission tomography associated with radio-tracers such as [18F]-fluorodeoxyglucose and the new [11C]-PK11195 in combination with computed tomography angiography to detect activated macrophages within the vessel wall. Imaging techniques are useful in the diagnostic work-up of large- and medium-vessel vasculitides, to monitor disease activity and the response to treatments. Finally, molecular imaging targets can provide new clues about the pathogenesis and evolution of immune-mediated disorders involving arterial vessels. PMID:25183963

  7. Non-invasive and invasive imaging of vulnerable coronary plaque.

    PubMed

    Celeng, Csilla; Takx, Richard A P; Ferencik, Maros; Maurovich-Horvat, Pál

    2016-08-01

    Vulnerable plaque is characterized by a large necrotic core and an overlying thin fibrous cap. Non-invasive imaging modalities such as computed tomography angiography (CTA) and magnetic resonance imaging (MRI) allow for the assessment of morphological plaque characteristics, while positron emission tomography (PET) enables the detection of metabolic activity within the atherosclerotic lesions. Invasive imaging modalities such as intravascular ultrasound (IVUS), optical-coherence tomography (OCT), and intravascular MRI (IV-MRI) display plaques at a high spatial resolution. Near-infrared spectroscopy (NIRS) allows for the detection of chemical components of atherosclerotic plaques. In this review, we describe state-of-the-art non-invasive and invasive imaging modalities and stress the combination of their advantages to identify vulnerable plaque features. PMID:27079893

  8. 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

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

    PubMed Central

    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. PMID:25525397

  10. Invasive and non-invasive modalities of imaging carotid stenosis.

    PubMed

    Tang, T Y; U-King-Im, J M; Walsh, S R; Young, V E; Sadat, U; Li, Z Y; Patterson, A J; Varty, K; Gillard, J H

    2009-12-01

    Despite recent therapeutic advances, acute ischemic complications of atherosclerosis remain the primary cause of morbidity and mortality in Western countries, with carotid atherosclerotic disease one of the major preventable causes of stroke. As the impact of this disease challenges our healthcare systems, we are becoming aware that factors influencing this disease are more complex than previously realized. In current clinical practice, risk stratification relies primarily on evaluation of the degree of luminal stenosis and patient symptomatology. Adequate investigation and optimal imaging are important factors that affect the quality of a carotid endarterectomy (CEA) service and are fundamental to patient selection. Digital subtraction angiography is still perceived as the most accurate imaging modality for carotid stenosis and historically has been the cornerstone of most of the major CEA trials but concerns regarding potential neurological complications have generated substantial interest in non-invasive modalities, such as contrast-enhanced magnetic resonance angiography. The purpose of this review is to give an overview to the vascular specialist of the current imaging modalities in clinical practice to identify patients with carotid stenosis. Advantages and disadvantages of each technique are outlined. Finally, limitations of assessing luminal stenosis in general are discussed. This article will not cover imaging of carotid atheroma morphology, function and other emerging imaging modalities of assessing plaque risk, which look beyond simple luminal measurements. PMID:19935602

  11. Autoimmune pancreatitis: Multimodality non-invasive imaging diagnosis.

    PubMed

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

    2014-12-01

    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

  12. 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

  13. 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

  14. 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

  15. Real time non invasive imaging of fatty acid uptake in vivo

    PubMed Central

    Henkin, Amy H.; Cohen, Allison S.; Dubikovskaya, Elena A.; Park, Hyo Min; Nikitin, Gennady F.; Auzias, Mathieu G.; Kazantzis, Melissa; Bertozzi, Carolyn R.; Stahl, Andreas

    2012-01-01

    Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin-sensitivity. To enable non-invasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). We show that this probe faithfully recapitulates cellular fatty acid uptake and can be used in animal systems as a valuable tool to localize and quantitate in real-time lipid fluxes such as intestinal fatty acid absorption and brown adipose tissue activation. This imaging approach should further our understanding of basic metabolic processes and pathological alterations in multiple disease models. PMID:22928772

  16. A non-invasive tissue-specific molecular delivery method of cancer gene therapy.

    PubMed

    Kodama, Tetsuya; Aoi, Atsuko; Vassaux, Georges; Mori, Shiro; Morikawa, Hidehiro; Koshiyama, Keni-Chiro; Yano, Takeru; Fujikawa, Shigeo; Tomita, Yukio

    2006-01-01

    A Japanese word, monozukuri (literally translated "making things") is the philosophy of first having the idea and then the faith in the technical expertise and experience to accomplish the result. We believe that the concept of engineering is monozukuri. Through the process of monozukuri, engineered natural science based on mathematics and physics has been developed. Medicine is the field of study which has been developed for maintaining daily healthy life with diagnosis, treatment, examination, and protection. Biomedical engineering is the interdisciplinary study of engineering and medicine, and should be developed based on monozukuri. In this particular research, we have developed a physical molecular delivery method for cancer gene therapy using nano/microbubbles and ultrasound. First, the behavior of cavitation bubbles and subsequent shock wave phenomena involved in the mechanism of molecular delivery were analyzed, combining theory and computer simulation. In a second step, the methodology was optimized in vitro and in vivo. Finally, the therapeutic potential of the method in pre-clinical models was evaluated using transgenes relevant to cancer gene therapy instead of reporter genes, and whole body, non-invasive imaging using single photon emission computed tomography (SPECT/CT) was used to evaluate the selectivity of gene delivery in vivo. PMID:16966136

  17. Non-invasive imaging through opaque scattering layers

    NASA Astrophysics Data System (ADS)

    Bertolotti, Jacopo; van Putten, E. G.; Blum, C.; Lagendijk, A.; Vos, W. L.; Mosk, A. P.

    2015-03-01

    Light scattering is known for blurring images to the point of making them appear as a white halo. For this reason imaging through thick clouds or deep into biological tissues is difficult. Here we discuss in details a method we developed recently to retrieve the shape of an object hidden behind a diffusing screen.

  18. Quantitative spectroscopic imaging for non-invasive early cancer detection.

    PubMed

    Yu, Chung-Chieh; Lau, Condon; O'Donoghue, Geoffrey; Mirkovic, Jelena; McGee, Sasha; Galindo, Luis; Elackattu, Alphi; Stier, Elizabeth; Grillone, Gregory; Badizadegan, Kamran; Dasari, Ramachandra R; Feld, Michael S

    2008-09-29

    We report a fully quantitative spectroscopy imaging instrument for wide area detection of early cancer (dysplasia). This instrument provides quantitative maps of tissue biochemistry and morphology, making it a potentially powerful surveillance tool for objective early cancer detection. We describe the design, construction, calibration, and first clinical application of this new system. We demonstrate its accuracy using physical tissue models. We validate its diagnostic ability on a resected colon adenoma, and demonstrate feasibility of in vivo imaging in the oral cavity. PMID:18825262

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26797565

  20. Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence

    PubMed Central

    Sumi, Natalia J.; Lima, Eydis; Pizzonia, John; Orton, Sean P.; Craveiro, Vinicius; Joo, Wonduk; Holmberg, Jennie C.; Gurrea, Marta; Yang-Hartwich, Yang; Alvero, Ayesha; Mor, Gil

    2014-01-01

    Epithelial ovarian cancer is the most lethal gynecologic malignancy in the United States. Although patients initially respond to the current standard of care consisting of surgical debulking and combination chemotherapy consisting of platinum and taxane compounds, almost 90% of patients recur within a few years. In these patients the development of chemoresistant disease limits the efficacy of currently available chemotherapy agents and therefore contributes to the high mortality. To discover novel therapy options that can target recurrent disease, appropriate animal models that closely mimic the clinical profile of patients with recurrent ovarian cancer are required. The challenge in monitoring intra-peritoneal (i.p.) disease limits the use of i.p. models and thus most xenografts are established subcutaneously. We have developed a sensitive optical imaging platform that allows the detection and anatomical location of i.p. tumor mass. The platform includes the use of optical reporters that extend from the visible light range to near infrared, which in combination with 2-dimensional X-ray co-registration can provide anatomical location of molecular signals. Detection is significantly improved by the use of a rotation system that drives the animal to multiple angular positions for 360 degree imaging, allowing the identification of tumors that are not visible in single orientation. This platform provides a unique model to non-invasively monitor tumor growth and evaluate the efficacy of new therapies for the prevention or treatment of recurrent ovarian cancer. PMID:25407815

  1. Non-invasive Imaging of Staphylococcus aureus Infections with a Nuclease-Activated Probe

    PubMed Central

    Hernandez, Frank J.; Huang, Lingyan; Olson, Michael E.; Powers, Kristy M.; Hernandez, Luiza I.; Meyerholz, David K.; Thedens, Daniel R.; Behlke, Mark A.; Horswill, Alexander R.; McNamara, James O.

    2013-01-01

    Technologies that enable the rapid detection and localization of bacterial infections in living animals could address an unmet need for infectious disease diagnostics. We describe a molecular imaging approach for the specific, non-invasive detection of S. aureus based on the activity of its secreted nuclease, micrococcal nuclease (MN). Several short, synthetic oligonucleotides, rendered resistant to mammalian serum nucleases by various chemical modifications, flanked with a fluorophore and quencher, were activated upon degradation by recombinant MN and in S. aureus culture supernatants. A probe consisting of a pair of deoxythymidines flanked by several 2′-O-methyl-modified nucleotides was activated in culture supernatants of S. aureus but not in culture supernatants of several other pathogenic bacteria. Systemic administration of this probe to mice bearing bioluminescent S. aureus muscle infections resulted in probe activation at the infection sites in an MN-dependent manner. This novel bacterial imaging approach has potential clinical applicability for S. aureus and several other medically significant pathogens. PMID:24487433

  2. [Cerebral arteriovenous malformations: value of the non invasive vascular imaging techniques].

    PubMed

    Leclerc, X; Gauvrit, J Y; Trystram, D; Reyns, N; Pruvo, J P; Meder, J F

    2004-12-01

    Imaging evaluation of cerebral arteriovenous malformations (AVM) requires selective visualization of the different compartments of the malformation in order to select the therapeutic management. Conventional angiography remains the reference to analyze intracranial vessel conspicuity but non-invasive methods constitute an excellent alternative. Among these techniques, CT angiography is rarely used because of the need to inject iodinated contrast material and because of irradiation. MR angiography provides useful information and can be performed using several techniques: time of flight with or without contrast material injection, phase contrast, three-dimensional (3D) gradient echo acquisition after contrast material injection and, more recently, MR digital subtraction angiography. The purpose of this review article is to summarize the different non-invasive techniques for vascular imaging and to analyze the usefulness of these techniques for the assessment of brain AVMs. PMID:15687950

  3. The potential of label-free nonlinear optical molecular microscopy to non-invasively characterize the viability of engineered human tissue constructs.

    PubMed

    Chen, Leng-Chun; Lloyd, William R; Kuo, Shiuhyang; Kim, Hyungjin Myra; Marcelo, Cynthia L; Feinberg, Stephen E; Mycek, Mary-Ann

    2014-08-01

    Nonlinear optical molecular imaging and quantitative analytic methods were developed to non-invasively assess the viability of tissue-engineered constructs manufactured from primary human cells. Label-free optical measures of local tissue structure and biochemistry characterized morphologic and functional differences between controls and stressed constructs. Rigorous statistical analysis accounted for variability between human patients. Fluorescence intensity-based spatial assessment and metabolic sensing differentiated controls from thermally-stressed and from metabolically-stressed constructs. Fluorescence lifetime-based sensing differentiated controls from thermally-stressed constructs. Unlike traditional histological (found to be generally reliable, but destructive) and biochemical (non-invasive, but found to be unreliable) tissue analyses, label-free optical assessments had the advantages of being both non-invasive and reliable. Thus, such optical measures could serve as reliable manufacturing release criteria for cell-based tissue-engineered constructs prior to human implantation, thereby addressing a critical regulatory need in regenerative medicine. PMID:24854093

  4. 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

  5. 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

  6. 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

  7. 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

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

    PubMed

    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

  9. 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

  10. A simple approach for non-invasive transcranial optical vascular imaging (nTOVI).

    PubMed

    Kalchenko, Vyacheslav; Israeli, David; Kuznetsov, Yuri; Meglinski, Igor; Harmelin, Alon

    2015-11-01

    In vivo imaging of cerebral vasculature is highly vital for clinicians and medical researchers alike. For a number of years non-invasive optical-based imaging of brain vascular network by using standard fluorescence probes has been considered as impossible. In the current paper controverting this paradigm, we present a robust non-invasive optical-based imaging approach that allows visualize major cerebral vessels at the high temporal and spatial resolution. The developed technique is simple to use, utilizes standard fluorescent dyes, inexpensive micro-imaging and computation procedures. The ability to clearly visualize middle cerebral artery and other major vessels of brain vascular network, as well as the measurements of dynamics of blood flow are presented. The developed imaging approach has a great potential in neuroimaging and can significantly expand the capabilities of preclinical functional studies of brain and notably contribute for analysis of cerebral blood circulation in disorder models. An example of 1 × 1.5 cm color-coded image of brain blood vessels of mouse obtained in vivo by transcranial optical vascular imaging (TOVI) approach through the intact cranium. PMID:25924020

  11. 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.

  12. Non-invasive, Multimodal Functional Imaging of the Intestine with Frozen Micellar Naphthalocyanines

    PubMed Central

    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.

    2014-01-01

    Overview 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 give rise to 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 (>1000). Unlike conventional chromophores, nanonaps exhibited 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 with 0.5 cm depth, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole body imaging. PMID:24997526

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Non-invasive in vivo imaging of calcium signaling in mice.

    PubMed

    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 Ca(2+) 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 Ca(2+) concentration ([Ca(2+)]) rises in live animals using bioluminescence imaging (BLI). Transgenic mice conditionally expressing the Ca(2+)-sensitive bioluminescent reporter GFP-aequorin targeted to the mitochondrial matrix were studied in several experimental paradigms. Rapid [Ca(2+)] rises inside the mitochondrial matrix could be readily detected during single-twitch muscle contractions. Whole body patterns of [Ca(2+)] were monitored in freely moving mice and during epileptic seizures. Furthermore, variations in mitochondrial [Ca(2+)] 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 Ca(2+) signaling whenever whole body information in freely moving animals is desired, in particular during behavioral and developmental studies. PMID:17912353

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Non-invasive diagnostics in pathological fossils by magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Mietchen, D.; Keupp, H.; Manz, B.; Volke, F.

    2005-03-01

    For more than a decade, Magnetic Resonance Imaging (MRI) has been routinely employed in clinical diagnostics because it allows to non-invasively study anatomical structures and physiological processes in vivo and to differentiate between healthy and pathological states, particularly in soft tissue. Here, we demonstrate that MRI can likewise be applied to fossilized biological samples and help in elucidating paleopathological and paleoecological questions: Five anomalous guards of Jurassic and Cretaceous belemnites are presented along with putative paleopathological scenarios directly derived from 3D Magnetic Resonance images with microscopic resolution. These syn vivo deformities of both the mineralized internal rostrum and the surrounding former soft tissue can be traced back in part to traumatic events of predator-prey-interactions, and partly to parasitism. Evidence is presented that the frequently observed anomalous apical collar might be indicative of an inflammatory disease. Finally, the potential of Magnetic Resonance techniques for further paleontological applications is being discussed.

  3. Non-invasive diagnostics in fossils - Magnetic Resonance Imaging of pathological belemnites

    NASA Astrophysics Data System (ADS)

    Mietchen, D.; Keupp, H.; Manz, B.; Volke, F.

    2005-06-01

    For more than a decade, Magnetic Resonance Imaging (MRI) has been routinely employed in clinical diagnostics because it allows non-invasive studies of anatomical structures and physiological processes in vivo and to differentiate between healthy and pathological states, particularly of soft tissue. Here, we demonstrate that MRI can likewise be applied to fossilized biological samples and help in elucidating paleopathological and paleoecological questions: Five anomalous guards of Jurassic and Cretaceous belemnites are presented along with putative paleopathological diagnoses directly derived from 3D MR images with microscopic resolution. Syn vivo deformities of both the mineralized internal rostrum and the surrounding former soft tissue can be traced back in part to traumatic events of predator-prey-interactions, and partly to parasitism. Besides, evidence is presented that the frequently observed anomalous apical collar might be indicative of an inflammatory disease. These findings highlight the potential of Magnetic Resonance techniques for further paleontological applications.

  4. 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. PMID:26137889

  5. 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.

  6. 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.

  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 Imaging of Neuroanatomical Structures and Neural Activation with High-Resolution MRI

    PubMed Central

    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. PMID:21503138

  9. Non-invasive single-shot imaging through scattering layers and around corners via speckle correlations

    NASA Astrophysics Data System (ADS)

    Katz, Ori; Heidmann, Pierre; Fink, Mathias; Gigan, Sylvain

    2014-10-01

    Optical imaging through and inside complex samples is a difficult challenge with important applications in many fields. The fundamental problem is that inhomogeneous samples such as biological tissue randomly scatter and diffuse light, preventing the formation of diffraction-limited images. Despite many recent advances, no current method can perform non-invasive imaging in real-time using diffused light. Here, we show that, owing to the ‘memory-effect’ for speckle correlations, a single high-resolution image of the scattered light, captured with a standard camera, encodes sufficient information to image through visually opaque layers and around corners with diffraction-limited resolution. We experimentally demonstrate single-shot imaging through scattering media and around corners using spatially incoherent light and various samples, from white paint to dynamic biological samples. Our single-shot lensless technique is simple, does not require wavefront-shaping nor time-gated or interferometric detection, and is realized here using a camera-phone. It has the potential to enable imaging in currently inaccessible scenarios.

  10. Bacterial Thymidine Kinase as a Non-Invasive Imaging Reporter for Mycobacterium tuberculosis in Live Animals

    PubMed Central

    Davis, Stephanie L.; Be, Nicholas A.; Lamichhane, Gyanu; Nimmagadda, Sridhar; Pomper, Martin G.; Bishai, William R.; Jain, Sanjay K.

    2009-01-01

    Background Bacteria can be selectively imaged in experimentally-infected animals using exogenously administered 1-(2′deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-[125I]-iodouracil ([125I]-FIAU), a nucleoside analog substrate for bacterial thymidine kinase (TK). Our goal was to use this reporter and develop non-invasive methods to detect and localize Mycobacterium tuberculosis. Methodology/Principal Findings We engineered a M. tuberculosis strain with chromosomally integrated bacterial TK under the control of hsp60 - a strong constitutive mycobacterial promoter. [125I]FIAU uptake, antimicrobial susceptibilities and in vivo growth characteristics were evaluated for this strain. Using single photon emission computed tomography (SPECT), M. tuberculosis Phsp60 TK strain was evaluated in experimentally-infected BALB/c and C3HeB/FeJ mice using the thigh inoculation or low-dose aerosol infection models. M. tuberculosis Phsp60 TK strain actively accumulated [125I]FIAU in vitro. Growth characteristics of the TK strain and susceptibility to common anti-tuberculous drugs were similar to the wild-type parent strain. M. tuberculosis Phsp60 TK strain was stable in vivo and SPECT imaging could detect and localize this strain in both animal models tested. Conclusion We have developed a novel tool for non-invasive assessment of M. tuberculosis in live experimentally-infected animals. This tool will allow real-time pathogenesis studies in animal models of TB and has the potential to simplify preclinical studies and accelerate TB research. PMID:19606217

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

    PubMed

    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

  12. 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

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

    PubMed

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

    2015-12-22

    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

  14. 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

  15. Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models

    PubMed Central

    Carney, Brandon; Carlucci, Giuseppe; Salinas, Beatriz; Di Gialleonardo, Valentina; Kossatz, Susanne; Vansteene, Axel; Longo, Valerie A.; Bolaender, Alexander; Chiosis, Gabriela; Keshari, Kayvan R.; Weber, Wolfgang A.; Reiner, Thomas

    2015-01-01

    Purpose The current study presents [18F]PARPi as imaging agent for PARP1 expression. Procedures [18F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[18F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/ magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma. Results [18F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC50=2.8±1.1 nM; logPCHI=2.15±0.41; plasma-free fraction=63.9±12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82±0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04±0.01 %ID/g. Conclusions [18F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions. PMID:26493053

  16. 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.

  17. Non-invasive in vivo imaging of early metabolic tumor response to therapies targeting choline metabolism.

    PubMed

    Mignion, Lionel; Danhier, Pierre; Magat, Julie; Porporato, Paolo E; Masquelier, Julien; Gregoire, Vincent; Muccioli, Giulio G; Sonveaux, Pierre; Gallez, Bernard; Jordan, Bénédicte F

    2016-04-15

    The cholinic phenotype, characterized by elevated phosphocholine and a high production of total-choline (tCho)-containing metabolites, is a metabolic hallmark of cancer. It can be exploited for targeted therapy. Non-invasive imaging biomarkers are required to evaluate an individual's response to targeted anticancer agents that usually do not rapidly cause tumor shrinkage. Because metabolic changes can manifest at earlier stages of therapy than changes in tumor size, the aim of the current study was to evaluate (1)H-MRS and diffusion-weighted MRI (DW-MRI) as markers of tumor response to the modulation of the choline pathway in mammary tumor xenografts. Inhibition of choline kinase activity was achieved with the direct pharmacological inhibitor H-89, indirect inhibitor sorafenib and down-regulation of choline-kinase α (ChKA) expression using specific short-hairpin RNA (shRNA). While all three strategies significantly decreased tCho tumor content in vivo, only sorafenib and anti-ChKA shRNA significantly repressed tumor growth. The increase of apparent-diffusion-coefficient of water (ADCw) measured by DW-MRI, was predictive of the induced necrosis and inhibition of the tumor growth in sorafenib treated mice, while the absence of change in ADC values in H89 treated mice predicted the absence of effect in terms of tumor necrosis and tumor growth. In conclusion, (1)H-choline spectroscopy can be useful as a pharmacodynamic biomarker for choline targeted agents, while DW-MRI can be used as an early marker of effective tumor response to choline targeted therapies. DW-MRI combined to choline spectroscopy may provide a useful non-invasive marker for the early clinical assessment of tumor response to therapies targeting choline signaling. PMID:26595604

  18. 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. PMID:26527222

  19. 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.

  20. Terahertz imaging systems: a non-invasive technique for the analysis of paintings

    NASA Astrophysics Data System (ADS)

    Fukunaga, K.; Hosako, I.; Duling, I. N., III; Picollo, M.

    2009-07-01

    Terahertz (THz) imaging is an emerging technique for non-invasive analysis. Since THz waves can penetrate opaque materials, various imaging systems that use THz waves have been developed to detect, for instance, concealed weapons, illegal drugs, and defects in polymer products. The absorption of THz waves by water is extremely strong, and hence, THz waves can be used to monitor the water content in various objects. THz imaging can be performed either by transmission or by reflection of THz waves. In particular, time domain reflection imaging uses THz pulses that propagate in specimens, and in this technique, pulses reflected from the surface and from the internal boundaries of the specimen are detected. In general, the internal structure is observed in crosssectional images obtained using micro-specimens taken from the work that is being analysed. On the other hand, in THz time-domain imaging, a map of the layer of interest can be easily obtained without collecting any samples. When realtime imaging is required, for example, in the investigation of the effect of a solvent or during the monitoring of water content, a THz camera can be used. The first application of THz time-domain imaging in the analysis of a historical tempera masterpiece was performed on the panel painting Polittico di Badia by Giotto, of the permanent collection of the Uffizi Gallery. The results of that analysis revealed that the work is composed of two layers of gypsum, with a canvas between these layers. In the paint layer, gold foils covered by paint were clearly observed, and the consumption or ageing of gold could be estimated by noting the amount of reflection. These results prove that THz imaging can yield useful information for conservation and restoration purposes.

  1. 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.

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

    PubMed

    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. PMID:27494561

  3. Graft complications following orthotopic liver transplantation: Role of non-invasive cross-sectional imaging techniques.

    PubMed

    Boraschi, Piero; Della Pina, Maria Clotilde; Donati, Francescamaria

    2016-07-01

    Orthotopic liver transplantation is the treatment of choice in adult patients with endstage liver disease. Survival of both graft and patient has progressively improved over time due to improvements in surgical and medical treatment. However, post-transplant complications still have a significant impact on morbidity and mortality associated with transplant surgery. The most common adverse events of the graft include vascular (arterial and venous stenosis and thrombosis), biliary (leakage, strictures, stones) and parenchymal complications (hepatitis virus C infection, HCC recurrence, liver abscesses). The diagnosis of these adverse events is often challenging because of the low specificity of clinical and biologic findings. Different diagnostic algorithms have been proposed for the detection of graft complications and, in this setting, radiological evaluation plays a key role in differential diagnosis of graft complications and the exclusion of other adverse events. Ultrasound examination is established the first-line method of identifying adverse events in liver transplant recipients but a normal or a technically unsatisfactory study cannot exclude the presence of biliary, vascular and/or parenchymal complications. In these circumstances, before planning any treatment, multi-detector CT and/or MR imaging and MR cholangiography should be performed for the evaluation of vascular structures, biliary system, liver parenchyma and fluid collections. The aim of this review is to illustrate the role and state-of-the-art of non-invasive cross-sectional imaging techniques in the diagnosis and management of complications which primarily affect the graft in patients after liver transplantation. PMID:27235874

  4. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2008-05-01

    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.

  6. 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. PMID:25990929

  7. Non-Invasive Imaging of Reactor Cores Using Cosmic Ray Muons

    NASA Astrophysics Data System (ADS)

    Milner, Edward

    2011-10-01

    Cosmic ray muons penetrate deeply in material, with some passing completely through very thick objects. This penetrating quality is the basis of two distinct, but related imaging techniques. The first measures the number of cosmic ray muons transmitted through parts of an object. Relatively fewer muons are absorbed along paths in which they encounter less material, compared to higher density paths, so the relative density of material is measured. This technique is called muon transmission imaging, and has been used to infer the density and structure of a variety of large masses, including mine overburden, volcanoes, pyramids, and buildings. In a second, more recently developed technique, the angular deflection of muons is measured by trajectory-tracking detectors placed on two opposing sides of an object. Muons are deflected more strongly by heavy nuclei, since multiple Coulomb scattering angle is approximately proportional to the nuclear charge. Therefore, a map showing regions of large deflection will identify the location of uranium in contrast to lighter nuclei. This technique is termed muon scattering tomography (MST) and has been developed to screen shipping containers for the presence of concealed nuclear material. Both techniques are a good way of non-invasively inspecting objects. A previously unexplored topic was applying MST to imaging large objects. Here we demonstrate extending the MST technique to the task of identifying relatively thick objects inside very thick shielding. We measured cosmic ray muons passing through a physical arrangement of material similar to a nuclear reactor, with thick concrete shielding and a heavy metal core. Newly developed algorithms were used to reconstruct an image of the ``mock reactor core,'' with resolution of approximately 30 cm.

  8. 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.

  9. 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. PMID:27422102

  10. 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.

  11. Characterising the myocardial interstitial space: the clinical relevance of non-invasive imaging.

    PubMed

    White, Steven K; Sado, Daniel M; Flett, Andrew S; Moon, James C

    2012-05-01

    The myocardial interstitial or extracellular space exists as a complex and dynamic environment, vital for normal cardiac structure and function. The physiological pathways for normal control of collagen turnover, and the pathological development of fibrosis are beginning to be understood, as are their relationships to cardiac remodelling and adverse outcomes. Emerging non-invasive imaging techniques (echocardiography, cardiovascular magnetic resonance, positron emission tomography) may allow a clearer understanding and measurement of these processes in vivo. Preliminary results are exciting, spanning valvular and congenital heart disease, cardiomyopathy and rarer diseases such as amyloid. In this review, such developments and research directions are explored, including the rapid developments in cardiovascular magnetic resonance T1 mapping and its use with contrast to derive extracellular volume. The authors present a state-of-the-art assessment of the strengths and weaknesses of each modality, and distil a framework to equip the reader with an understanding of the technical issues useful for the interpretation of emerging clinical studies. PMID:22422587

  12. 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.

  13. 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

  14. 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

  15. Imaging human brain networks to improve the clinical efficacy of non-invasive brain stimulation.

    PubMed

    Sale, Martin V; Mattingley, Jason B; Zalesky, Andrew; Cocchi, Luca

    2015-10-01

    The flexible integration of segregated neural processes is essential to healthy brain function. Advances in neuroimaging techniques have revealed that psychiatric and neurological disorders are characterized by anomalies in the dynamic integration of widespread neural populations. Re-establishing optimal neural activity is an important component of the treatment of such disorders. Non-invasive brain stimulation is emerging as a viable tool to selectively restore both local and widespread neural activity in patients affected by psychiatric and neurological disorders. Importantly, the different forms of non-invasive brain stimulation affect neural activity in distinct ways, which has important ramifications for their clinical efficacy. In this review, we discuss how non-invasive brain stimulation techniques influence widespread neural integration across brain regions. We suggest that the efficacy of such techniques in the treatment of psychiatric and neurological conditions is contingent on applying the appropriate stimulation paradigm to restore specific aspects of altered neural integration. PMID:26409343

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. The investigation of Mitogen-Activated Protein kinase Phosphatase-1 as a potential pharmacological target in non-small cell lung carcinomas, assisted by non-invasive molecular imaging

    PubMed Central

    2010-01-01

    Background Invasiveness and metastasis are the most common characteristics of non small cell lung cancer (NSCLC) and causes of tumour-related morbidity and mortality. Mitogen-activated protein kinases (MAPKs) signalling pathways have been shown to play critical roles in tumorigenesis. However, the precise pathological role(s) of mitogen-activated protein kinase phosphatase-1 (MKP-1) in different cancers has been controversial such that the up-regulation of MKP-1 in different cancers does not always correlate to a better prognosis. In this study, we showed that the induction of MKP-1 lead to a significant retardation of proliferation and metastasis in NSCLC cells. We also established that rosiglitazone (a PPARγ agonist) elevated MKP-1 expression level in NSCLC cells and inhibited tumour metastasis. Methods Both wildtype and dominant negative forms of MKP-1 were constitutively expressed in NSCLC cell line H441GL. The migration and invasion abilities of these cells were examined in vitro. MKP-1 modulating agents such as rosiglitazone and triptolide were used to demonstrate MKP-1's role in tumorigenesis. Bioluminescent imaging was utilized to study tumorigenesis of MKP-1 over-expressing H441GL cells and anti-metastatic effect of rosiglitazone. Results Over-expression of MKP-1 reduced NSCLC cell proliferation rate as well as cell invasive and migratory abilities, evident by the reduced expression levels of MMP-2 and CXCR4. Mice inoculated with MKP-1 over-expressing H441 cells did not develop NSCLC while their control wildtype H441 inoculated littermates developed NSCLC and bone metastasis. Pharmacologically, rosiglitazone, a peroxisome proliferator activated receptor-γ (PPARγ) agonist appeared to induce MKP-1 expression while reduce MMP-2 and CXCR4 expression. H441GL-inoculated mice receiving daily oral rosiglitazone treatment demonstrated a significant inhibition of bone metastasis when compared to mice receiving sham treatment. We found that rosiglitazone treatment

  18. High-resolution harmonics ultrasound imaging for non-invasive characterization of wound healing in a pre-clinical swine model.

    PubMed

    Gnyawali, Surya C; Barki, Kasturi G; 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

  19. 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

  20. 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

  1. Non-Invasive Imaging for Studying Anti-Angiogenic Therapy Effects

    PubMed Central

    Ehling, Josef; Lammers, Twan; Kiessling, Fabian

    2013-01-01

    Noninvasive imaging plays an emerging role in preclinical and clinical cancer research and has high potential to improve clinical translation of new drugs. This article summarizes and discusses tools and methods to image tumor angiogenesis and monitor anti-angiogenic therapy effects. In this context, micro-computed tomography (μCT) is recommended to visualize and quantify the micro-architecture of functional tumor vessels. Contrast-enhanced ultrasound (US) and magnetic resonance imaging (MRI) are favorable tools to assess functional vascular parameters, such as perfusion and relative blood volume. These functional parameters have been shown to indicate anti-angiogenic therapy response at an early stage, before changes in tumor size appear. For tumor characterization, the imaging of the molecular characteristics of tumor blood vessels, such as receptor expression, might have an even higher diagnostic potential and has been shown to be highly suitable for therapy monitoring as well. In this context, US using targeted microbubbles is currently evaluated in clinical trials as an important tool for the molecular characterization of the angiogenic endothelium. Other modalities, being preferably used for molecular imaging of vessels and their surrounding stroma, are photoacoustic imaging (PAI), near-infrared fluorescence optical imaging (OI), MRI, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The latter two are particularly useful if very high sensitivity is needed, and/or if the molecular target is difficult to access. Carefully considering the pros and cons of different imaging modalities in a multimodal imaging setup enables a comprehensive longitudinal assessment of the (micro)morphology, function and molecular regulation of tumor vessels. PMID:23407722

  2. 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

  3. 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

  4. 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

  5. Non-invasive evaluation of arrhythmic risk in dilated cardiomyopathy: From imaging to electrocardiographic measures

    PubMed Central

    Iacoviello, Massimo; Monitillo, Francesco

    2014-01-01

    Malignant ventricular arrhythmias are a major adverse event and worsen the prognosis of patients affected by ischemic and non-ischemic dilated cardiomyopathy. The main parameter currently used to stratify arrhythmic risk and guide decision making towards the implantation of a cardioverter defibrillator is the evaluation of the left ventricular ejection fraction. However, this strategy is characterized by several limitations and consequently additional parameters have been suggested in order to improve arrhythmic risk stratification. The aim of this review is to critically revise the prognostic significance of non-invasive diagnostic tools in order to better stratify the arrhythmic risk prognosis of dilated cardiomyopathy patients. PMID:25068017

  6. 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.

  7. Non-invasive imaging to monitor lupus nephritis and neuropsychiatric systemic lupus erythematosus

    PubMed Central

    Thurman, Joshua M.; Serkova, Natalie J.

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple different organs, including the kidneys and central nervous system (CNS). Conventional radiological examinations in SLE patients include volumetric/ anatomical computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US). The utility of these modalities is limited, however, due to the complexity of the disease. Furthermore, standard CT and MRI contrast agents are contraindicated in patients with renal impairment. Various radiologic methods are currently being developed to improve disease characterization in patients with SLE beyond simple anatomical endpoints. Physiological non-contrast MRI protocols have been developed to assess tissue oxygenation, glomerular filtration, renal perfusion, interstitial diffusion, and inflammation-driven fibrosis in lupus nephritis (LN) patients. For neurological symptoms, vessel size imaging (VSI, an MRI approach utilizing T2-relaxing iron oxide nanoparticles) has shown promise as a diagnostic tool. Molecular imaging probes (mostly for MRI and nuclear medicine imaging) have also been developed for diagnosing SLE with high sensitivity, and for monitoring disease activity. This paper reviews the challenges in evaluating disease activity in patients with LN and neuropsychiatric systemic lupus erythematosus (NPSLE). We describe novel MRI and positron-emission tomography (PET) molecular imaging protocols using targeted iron oxide nanoparticles and radioactive ligands, respectively, for detection of SLE-associated inflammation. PMID:26309728

  8. 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. PMID:23312298

  9. The impact of oxidative stress on islet transplantation and monitoring the graft survival by non-invasive imaging.

    PubMed

    Ramkumar, K M; Sekar, T V; Bhakkiyalakshmi, E; Foygel, Kira; Rajaguru, P; Berger, F; Paulmurugan, R

    2013-01-01

    and C-peptide levels. These biochemical measurements provide markers at only the late stages of islet rejection. Use of molecular imaging techniques has the potential for real-time non-invasive monitoring of the functional status and viability of transplanted islet grafts in living animals. This review mainly focuses on the current status of islet transplantations, potential preventive strategies used to reduce oxidative stress-mediated toxicity in islet grafts, and use of molecular imaging as a tool to quantitatively evaluate the functional status of the transplanted islets in living animals. PMID:23317098

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Irradiation, Cisplatin, and 5-Azacytidine Upregulate Cytomegalovirus Promoter in Tumors and Muscles: Implementation of Non-invasive Fluorescence Imaging

    PubMed Central

    Kamensek, Urska; Sersa, Gregor; Vidic, Suzana; Tevz, Gregor; Kranjc, Simona

    2010-01-01

    Purpose The cytomegalovirus (CMV) promoter is one of the most commonly used promoters for expression of transgenes in mammalian cells. The aim of our study was to evaluate the role of methylation and upregulation of the CMV promoter by irradiation and the chemotherapeutic agent cisplatin in vivo using non-invasive fluorescence in vivo imaging. Procedures Murine fibrosarcoma LPB and mammary carcinoma TS/A cells were stably transfected with plasmids encoding CMV and p21 promoter-driven green fluorescent protein (GFP) gene. Solid TS/A tumors were induced by subcutaneous injection of fluorescent tumor cells, while leg muscles were transiently transfected with plasmid encoding GFP under the control of the CMV promoter. Cells, tumors, and legs were treated either by DNA methylation inhibitor 5-azacytidine, irradiation, or cisplatin. GFP expression was determined using a fluorescence microplate reader in vitro and by non-invasive fluorescence imaging in vivo. Results Treatment of cells, tumors, and legs with 5-azacytidine (re)activated the CMV promoter. Furthermore, treatment with irradiation or cisplatin resulted in significant upregulation of GFP expression both in vitro and in vivo. Conclusions Observed alterations in the activity of the CMV promoter limit the usefulness of this widely used promoter as a constitutive promoter. On the other hand, inducibility of CMV promoters can be beneficially used in gene therapy when combined with standard cancer treatment, such as radiotherapy and chemotherapy. PMID:20396957

  16. USPIO-labeled textile materials for non-invasive MR imaging of tissue-engineered vascular grafts.

    PubMed

    Mertens, Marianne E; Koch, Sabine; Schuster, Philipp; Wehner, Jakob; Wu, Zhuojun; Gremse, Felix; Schulz, Volkmar; Rongen, Lisanne; Wolf, Frederic; Frese, Julia; Gesché, Valentine N; van Zandvoort, Marc; Mela, Petra; Jockenhoevel, Stefan; Kiessling, Fabian; Lammers, Twan

    2015-01-01

    Non-invasive imaging might assist in the clinical translation of tissue-engineered vascular grafts (TEVG). It can e.g. be used to facilitate the implantation of TEVG, to longitudinally monitor their localization and function, and to provide non-invasive and quantitative feedback on their remodeling and resorption. We here incorporated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles into polyvinylidene fluoride (PVDF)-based textile fibers, and used them to prepare imageable tissue-engineered vascular grafts (iTEVG). The USPIO-labeled scaffold materials were molded with a mixture of fibrin, fibroblasts and smooth muscle cells, and then endothelialized in a bioreactor under physiological flow conditions. The resulting grafts could be sensitively detected using T1-, T2- and T2*-weighted MRI, both during bioreactor cultivation and upon surgical implantation into sheep, in which they were used as an arteriovenous shunt between the carotid artery and the jugular vein. In vivo, the iTEVG were shown to be biocompatible and functional. Post-mortem ex vivo analyses provided evidence for efficient endothelialization and for endogenous neo-vascularization within the biohybrid vessel wall. These findings show that labeling polymer-based textile materials with MR contrast agents is straightforward and safe, and they indicate that such theranostic tissue engineering approaches might be highly useful for improving the production, performance, personalization and translation of biohybrid vascular grafts. PMID:25465443

  17. 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.

  18. 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

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

    PubMed

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

    2015-03-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

    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.

  1. Functional photoacoustic tomography for non-invasive imaging of cerebral blood oxygenation and blood volume in rat brain in vivo

    NASA Astrophysics Data System (ADS)

    Wang, Xueding; Xie, Xueyi; Ku, Geng; Stoica, George; Wang, Lihong V.

    2005-04-01

    Based on the multi-wavelength laser-based photoacoustic tomography, non-invasive in vivo imaging of functional parameters, including the hemoglobin oxygen saturation and the total concentration of hemoglobin, in small-animal brains was realized. The high sensitivity of this technique is based on the spectroscopic differences between oxy- and deoxy-hemoglobin while its spatial resolution is bandwidth-limited by the photoacoustic signals rather than by the optical diffusion as in optical imaging. The point-by-point distributions of blood oxygenation and blood volume in the cerebral cortical venous vessels, altered by systemic physiological modulations including hyperoxia, normoxia and hypoxia, were visualized successfully through the intact skin and skull. This technique, with its prominent intrinsic advantages, can potentially accelerate the progress in neuroscience and provide important new insights into cerebrovascular physiology and brain function that are of great significance to the neuroscience community.

  2. [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. PMID:25807773

  3. 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. PMID:26489364

  4. 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

  5. Diagnosing Bladder Outlet Obstruction Using Non-invasive Decorrelation-Based Ultrasound Imaging: A Feasibility Study in Healthy Male Volunteers.

    PubMed

    Arif, Muhammad; Idzenga, Tim; van Mastrigt, Ron; de Korte, Chris L

    2015-12-01

    A feasibility study on the applicability of an ultrasound decorrelation method to urinary flow imaging was carried out in 20 healthy male volunteers, to provide a basis for a non-invasive approach to diagnose bladder outlet obstruction. Each volunteer voided five times in a flow meter in standing position. During each voiding, ultrasound radiofrequency frames were acquired transperineally at different flow rates. The results indicated that the decrease in correlation (decorrelation) of ultrasound radiofrequency signals had no unique relation with flow rate, but decreased distinctively with urinary flow velocity. In most of the healthy volunteers, the decorrelation was small because of the low flow velocity. However, because of the different flow velocities in volunteers, the variation in slope between volunteers was statistically significant. Therefore, it is probably possible to use the decorrelation method to differentiate between healthy persons and patients with obstruction. PMID:26403699

  6. 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

  7. Non-invasive detection of liver fibrosis: MR imaging features vs. MR elastography

    PubMed Central

    Venkatesh, Sudhakar K.; Yin, Meng; Takahashi, Naoki; Glockner, James F.; Talwalkar, Jayant A.; Ehman, Richard L.

    2016-01-01

    Purpose To compare accuracy of morphological features of liver on MRI and liver stiffness with MR elastography (MRE) for detection of significant liver fibrosis and cirrhosis. Materials and Methods In this retrospective study, we evaluated 62 patients who underwent liver MRI with MRE and histological confirmation of liver fibrosis within 6 months. Two radiologists, blinded to histology results, independently evaluated liver parenchyma texture, surface nodularity, signs of volumetric changes and portal hypertension for presence of significant fibrosis and cirrhosis. Two more readers independently calculated mean liver stiffness values with MRE. Interobserver agreement was evaluated with kappa and intra-class correlation coefficient (ICC) analysis. Diagnostic accuracy was assessed with area under receiver operating characteristic (AUROC) analysis. Comparison of AUROCs of MRI and MRE was performed. Results Liver fibrosis was present in 37 patients. The interobserver agreement was poor to good (kappa= 0.12 - 0.74) for MRI features and excellent for MRE (ICC, 0.97, 95% CI, 0.95-0.98). MRI features had 48.5-87.9%sensitivity, 55.2%-100%specificity and 71.5-81.6% accuracy //for detection of significant fibrosis. MRE performed better with 100% sensitivity, 96.5% specificity and 98.9% accuracy .For the detection of cirrhosis, MRE performed better than MRI features with 88.2% sensitivity (vs.41.2-82.3%), 91.1% specificity (vs. 64.4-95.6%) and 93.5% accuracy (vs. 60.6%-80.5%) Among the MRI features, surface nodularity and overall impression had the best accuracies of 80.3% and 81.6% for detection of significant fibrosis respectively. For cirrhosis, parenchyma texture and overall impression had the best accuracies of 80.5% and 79.7% respectively . Overall, MRE had significantly greater AUROC than MRI features for detection of both significant fibrosis (0.98.9 vs 0.71-0.82, p<0.001) and cirrhosis (0.93.5-vs. 0.61 -0.80.5, p<0.01). Conclusion MRE is superior to MRI for the non-invasive

  8. Non-Invasive Magnetic Resonance Imaging in Rats for Prediction of the Fate of Grafted Kidneys from Cardiac Death Donors

    PubMed Central

    Kaimori, Jun-Ya; Iwai, Satomi; Hatanaka, Masaki; Teratani, Takumi; Obi, Yoshitsugu; Tsuda, Hidetoshi; Isaka, Yoshitaka; Yokawa, Takashi; Kuroda, Kagayaki; Ichimaru, Naotsugu; Okumi, Masayoshi; Yazawa, Koji; Rakugi, Hiromi; Nonomura, Norio; Takahara, Shiro; Kobayashi, Eiji

    2013-01-01

    The main objective of this study was to assess cardiac death (CD) kidney grafts before transplantation to determine whether blood oxygen level-dependent (BOLD) and diffusion MRI techniques can predict damage to these grafts after transplantation. We assessed CD kidney tissue by BOLD and diffusion MRI. We also examined pathological and gene expression changes in CD kidney grafts before and after transplantation. Although there was significantly more red cell congestion (RCC) in the inner stripe of the outer medulla (IS) in both 1 h after cardiac death (CD1h) and CD2h kidneys destined for grafts before transplantation compared with CD0h (p<0.05), CD2h, but not CD1h, kidney grafts had significantly different RCC in the IS 2 days after transplantation (p<0.05). Consistent with these pathological findings, tissue plasminogen activator (tPA) gene expression was increased only in the cortex and medulla of CD2h kidney grafts after transplantation. BOLD MRI successfully and non-invasively imaged and quantified RCC in the IS in both CD1h and CD2h kidney grafts (p<0.05). Diffusion MRI also non-invasively assessed increased the apparent diffusion coefficient in the IS and decreased it in the outer stripe (OS) of CD2h grafts, in concordance with interstitial edema in the IS and tubule cellular edema in the OS. These two types of edema in the outer medulla could explain the prolonged RCC in the IS only of CD2h kidney grafts, creating part of a vicious cycle inhibiting red cells coming out of capillary vessels in the IS. Perfusion with University of Wisconsin solution before MRI measurements did not diminish the difference in tissue damage between CD1h and CD2h kidney grafts. BOLD and diffusion MRI, which are readily available non-invasive tools for evaluating CD kidney grafts tissue damage, can predict prolonged organ damage, and therefore the outcome, of transplanted CD kidney grafts. PMID:23667641

  9. 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.

  10. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014).

    PubMed

    Ceyssens, Pieter-Jan; Van Bambeke, Françoise; Mattheus, Wesley; Bertrand, Sophie; Fux, Frédéric; Van Bossuyt, Eddie; Damée, Sabrina; Nyssen, Henry-Jean; De Craeye, Stéphane; Verhaegen, Jan; Tulkens, Paul M; Vanhoof, Raymond

    2016-01-01

    We present the results of a longitudinal surveillance study (1995-2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. PMID:27227336

  11. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)

    PubMed Central

    Ceyssens, Pieter-Jan; Van Bambeke, Françoise; Mattheus, Wesley; Bertrand, Sophie; Fux, Frédéric; Van Bossuyt, Eddie; Damée, Sabrina; Nyssen, Henry-Jean; De Craeye, Stéphane; Verhaegen, Jan; Tulkens, Paul M.; Vanhoof, Raymond

    2016-01-01

    We present the results of a longitudinal surveillance study (1995–2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. PMID:27227336

  12. 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.

  13. 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.

  14. 3-D SPECTRAL IP IMAGING: NON-INVASIVE CHARACTERIZATION OF CONTAMINANT PLUMES

    EPA Science Inventory

    The objective of this study is to develop a noninvasive tomographic imaging technique,based on the spectral induced-polarization method, to characterize the in-situ distribution of organic and inorganic groundwater contaminants. Recent advances in tomographic imaging, applied to ...

  15. 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.

  16. 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

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

    PubMed Central

    Lorbergs, Amanda L.

    2012-01-01

    ABSTRACT 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. PMID:23449969

  18. 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.

  19. A review of non-invasive optical-based image analysis systems for continuous bioprocess monitoring.

    PubMed

    Höpfner, Tim; Bluma, Arne; Rudolph, Guido; Lindner, Patrick; Scheper, Thomas

    2010-02-01

    To observe and control cultivation processes, optical sensors are used increasingly. Important variables for controlling such processes are cell count, cell size distribution and the morphology of cells. Among turbidity measurement methods, imaging procedures are applied for determining these process values. A disadvantage of most previously developed imaging procedures is that they are only available offline, which requires sampling. On the other hand, available imaging inline probes can only deliver a limited number of process values so far. This contribution gives an overview of optical procedures for the inline determination of cell count, cell size distribution and other variables. In particular, by in situ microscopy, an imaging procedure will be described, which allows the determination of direct and non-direct cell variables in real time without sampling. PMID:19396466

  20. 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

  1. Continuing education course #1: non-invasive imaging as a problem-solving tool and translational biomarker strategy in toxicologic pathology.

    PubMed

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

    2011-01-01

    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 nonterminal, time-course evaluation of functional and morphologic endpoints and can be used to translate biomarkers between preclinical animal models and human patients. NIN 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

  2. Tomographic imaging of holographic GPR data for non-invasive structural assessment: the Musmeci bridge investigation

    NASA Astrophysics Data System (ADS)

    Catapano, I.; Crocco, L.; Morabito, A. F.; Soldovieri, F.

    2012-09-01

    The monitoring of the structural integrity of critical transport infrastructures is extremely important in order to prevent accidents, disasters and ensure urban safety. For this reason, several remote and in situ nondestructive electromagnetic technologies have been exploited as diagnostic tools, from which it is possible to obtain information and images of the infrastructure inner status at different spatial and temporal scales. In this framework, this paper deals with holographic ground-penetrating radar tomographic imaging, used as an in situ diagnostic tool to provide high-resolution images of shallowly buried metallic and dielectric objects. As a matter of fact, the need of integrating information gathered at different scales for a global assessment of the structure health makes the (local and high resolution) image obtained by means of this technique particularly valuable. In particular, we consider the Rascan-4/4000 radar system coupled with a tomographic imaging approach specifically tailored to process holographic data, which is adopted to improve the achievable spatial resolution. A proof of concept of the reconstruction capabilities is given against laboratory data. Moreover, on-field examples in the framework of concrete structures monitoring are shown by processing data collected at the Musmeci bridge in Potenza, Italy.

  3. 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.

  4. Non-Invasive and Minimally Invasive Imaging Evaluation of CSF Rhinorrhoea – a Retrospective Study with Review of Literature

    PubMed Central

    Vimala, Leena Robinson; Jasper, Anitha; Irodi, Aparna

    2016-01-01

    Summary Background Localization of a cerebrospinal fluid [CSF] fistula is a diagnostic challenge. The choice of an optimal imaging technique is necessary to locate the site of CSF leak which is required for surgical/endoscopic repair of the CSF fistula. Material/Methods Retrospective analysis of imaging was performed in 33 patients who presented with symptoms suggestive of CSF rhinorrhoea over a period of two years. Either a bone defect on high resolution CT [HRCT] or CSF column extending extracranially from the subarachnoid space with or without brain/ meningeal herniation on magnetic resonance [MR] cisternography was considered positive for CSF leak. The MR imaging technique included 1-mm heavily T2-weighted [TR 2000 ms; TE-200 ms] fast spin echo study in coronal and sagittal planes. HRCT sections involved 0.625 to 0.8-mm sections in the coronal plane, with or without axial planes, through the paranasal sinuses, reconstructed in a sharp algorithm and acquired with the patient in prone position. Imaging findings were compared with endoscopic findings, being the gold standard for the assessment of CSF rhinorrhea. Results A total of 25 patients had a combination of HRCT and MR cisternography. The sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV] of both MR cisternography and HRCT together were 93%, 100%, 100% and 50% respectively. Two patients underwent only MR cisternography, 5 patients underwent only HRCT and one patient underwent HRCT, MR cisternography and CT cisternography. Though PPV was 100% in the groups with HRCT alone, MR cisternography alone and combined CT cisternography, HRCT and MR cisternography, the results were not statistically significant as the number of patients in those groups was lower. Conclusions Combination of MR cisternography and HRCT appears to be complementary, accurate and non-invasive and should be considered as optimal imaging modality for pre-op imaging in the evaluation of CSF rhinorrhoea

  5. A novel imaging platform for non-invasive screening of abnormal glucose tolerance.

    PubMed

    Jeong, Bosu; Jung, Chang Hee; Lee, Yong-Ho; Shin, Il-Hyung; Kim, Hansuk; Bae, Soo-Jin; Lee, Dae-Sic; Kang, Eun Seok; Kang, Uk; Kim, Jong Jin; Park, Joong-Yeol

    2016-06-01

    Optical measurement of skin auto-fluorescence (SAF), most likely emanating from accumulated advanced glycation end-products (AGEs), has been proposed for the noninvasive diagnosis of glucose intolerance in clinical settings. Here, we developed a novel imaging system with transmission geometry for SAF measurement and compared its diagnostic performance in a Korean population. PMID:27321320

  6. 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

  7. 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

  8. Non-invasive Imaging of the Innate Immune Response in a Zebrafish Larval Model of Streptococcus iniae Infection

    PubMed Central

    Harvie, Elizabeth A.; Huttenlocher, Anna

    2015-01-01

    The aquatic pathogen, Streptococcus iniae, is responsible for over 100 million dollars in annual losses for the aquaculture industry and is capable of causing systemic disease in both fish and humans. A better understanding of S. iniae disease pathogenesis requires an appropriate model system. The genetic tractability and the optical transparency of the early developmental stages of zebrafish allow for the generation and non-invasive imaging of transgenic lines with fluorescently tagged immune cells. The adaptive immune system is not fully functional until several weeks post fertilization, but zebrafish larvae have a conserved vertebrate innate immune system with both neutrophils and macrophages. Thus, the generation of a larval infection model allows the study of the specific contribution of innate immunity in controlling S. iniae infection. The site of microinjection will determine whether an infection is systemic or initially localized. Here, we present our protocols for otic vesicle injection of zebrafish aged 2-3 days post fertilization as well as our techniques for fluorescent confocal imaging of infection. A localized infection site allows observation of initial microbe invasion, recruitment of host cells and dissemination of infection. Our findings using the zebrafish larval model of S. iniae infection indicate that zebrafish can be used to examine the differing contributions of host neutrophils and macrophages in localized bacterial infections. In addition, we describe how photolabeling of immune cells can be used to track individual host cell fate during the course of infection. PMID:25938624

  9. Non-invasive measurement of choroidal volume change and ocular rigidity through automated segmentation of high-speed OCT imaging

    PubMed Central

    Beaton, L.; Mazzaferri, J.; Lalonde, F.; Hidalgo-Aguirre, M.; Descovich, D.; Lesk, M. R.; Costantino, S.

    2015-01-01

    We have developed a novel optical approach to determine pulsatile ocular volume changes using automated segmentation of the choroid, which, together with Dynamic Contour Tonometry (DCT) measurements of intraocular pressure (IOP), allows estimation of the ocular rigidity (OR) coefficient. Spectral Domain Optical Coherence Tomography (OCT) videos were acquired with Enhanced Depth Imaging (EDI) at 7Hz during ~50 seconds at the fundus. A novel segmentation algorithm based on graph search with an edge-probability weighting scheme was developed to measure choroidal thickness (CT) at each frame. Global ocular volume fluctuations were derived from frame-to-frame CT variations using an approximate eye model. Immediately after imaging, IOP and ocular pulse amplitude (OPA) were measured using DCT. OR was calculated from these peak pressure and volume changes. Our automated segmentation algorithm provides the first non-invasive method for determining ocular volume change due to pulsatile choroidal filling, and the estimation of the OR constant. Future applications of this method offer an important avenue to understanding the biomechanical basis of ocular pathophysiology. PMID:26137373

  10. FMN-Coated Fluorescent USPIO for Cell Labeling and Non-Invasive MR Imaging in Tissue Engineering

    PubMed Central

    Mertens, Marianne E.; Frese, Julia; Bölükbas, Deniz Ali; Hrdlicka, Ladislav; Golombek, Susanne; Koch, Sabine; Mela, Petra; Jockenhövel, Stefan; Kiessling, Fabian; Lammers, Twan

    2014-01-01

    Non-invasive magnetic resonance imaging (MRI) is gaining significant attention in the field of tissue engineering, since it can provide valuable information on in vitro production parameters and in vivo performance. It can e.g. be used to monitor the morphology, location and function of the regenerated tissue, the integrity, remodeling and resorption of the scaffold, and the fate of the implanted cells. Since cells are not visible using conventional MR techniques, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are routinely employed to label and monitor the cells embedded in tissue-engineered implants. We here set out to optimize cell labeling procedures with regard to labeling efficiency, biocompatibility and in vitro validation during bioreactor cultivation, using flavin mononucleotide (FMN)-coated fluorescent USPIO (FLUSPIO). Efficient FLUSPIO uptake is demonstrated in three different cell lines, applying relatively short incubation times and low labeling concentrations. FLUSPIO-labeled cells were successfully employed to visualize collagen scaffolds and tissue-engineered vascular grafts. Besides promoting safe and efficient cell uptake, an exquisite property of the non-polymeric FMN-coating is that it renders the USPIO fluorescent, providing a means for in vitro, in vivo and ex vivo validation via fluorescence microscopy and fluorescence reflectance imaging (FRI). FLUSPIO cell labeling is consequently considered to be a suitable tool for theranostic tissue engineering purposes. PMID:25157279

  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. Non-invasive imaging of allogeneic transplanted skin graft by 131I-anti-TLR5 mAb.

    PubMed

    Sun, Hukui; Yang, Guangjie; Liang, Ting; Zhang, Chao; Song, Jing; Han, Jiankui; Hou, Guihua

    2014-12-01

    Although (18)F-fluorodeoxyglucose ((18)F-FDG) uptake can be used for the non-invasive detection and monitoring of allograft rejection by activated leucocytes, this non-specific accumulation is easily impaired by immunosuppressants. Our aim was to evaluate a (131)I-radiolabelled anti-Toll-like receptor 5 (TLR5) mAb for non-invasive in vivo graft visualization and quantification in allogeneic transplantation mice model, compared with the non-specific radiotracer (18)F-FDG under using of immunosuppressant. Labelling, binding, and stability studies were performed. BALB/c mice transplanted with C57BL/6 skin grafts, with or without rapamycin treatment (named as allo-treated group or allo-rejection group), were injected with (131)I-anti-TLR5 mAb, (18)F-FDG, or mouse isotype (131)I-IgG, respectively. Whole-body phosphor-autoradiography and ex vivo biodistribution studies were obtained. Whole-body phosphor-autoradiography showed (131)I-anti-TLR5 mAb uptake into organs that were well perfused with blood at 1 hr and showed clear graft images from 12 hrs onwards. The (131)I-anti-TLR5 mAb had significantly higher graft uptake and target-to-non-target ratio in the allo-treated group, as determined by semi-quantification of phosphor-autoradiography images; these results were consistent with ex vivo biodistribution studies. However, high (18)F-FDG uptake was not observed in the allo-treated group. The highest allograft-skin-to-native-skin ratio (A:N) of (131)I-anti-TLR5 mAb uptake was significantly higher than the ratio for (18)F-FDG (7.68 versus 1.16, respectively). (131)I-anti-TLR5 mAb uptake in the grafts significantly correlated with TLR5 expression in the allograft area. The accumulation of (131)I-IgG was comparable in both groups. We conclude that radiolabelled anti-TLR5 mAb is capable of detecting allograft with high target specificity after treatment with the immunosuppressive drug rapamycin. PMID:25283154

  13. 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.

  14. 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. PMID:21308945

  15. 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.

  16. Comparison of electrical velocimetry and cardiac magnetic resonance imaging for the non-invasive determination of cardiac output.

    PubMed

    Trinkmann, Frederik; Berger, Manuel; Doesch, Christina; Papavassiliu, Theano; Schoenberg, Stefan O; Borggrefe, Martin; Kaden, Jens J; Saur, Joachim

    2016-08-01

    A novel algorithm of impedance cardiography referred to as electrical velocimetry (EV) has been introduced for non-invasive determination of cardiac output (CO). Previous validation studies yielded diverging results and no comparison with the non-invasive gold standard cardiac magnetic resonance imaging (CMR) has been performed. We therefore aimed to prospectively assess the accuracy and reproducibility of EV compared to CMR. 152 consecutive stable patients undergoing CMR were enrolled. EV measurements were taken twice before or after CMR in supine position and averaged over 20 s (AESCULON(®), Osypka Medical, Berlin, Germany). Bland-Altman analysis showed insufficient agreement of EV and CMR with a mean bias of 1.2 ± 1.4 l/min (bias 23 ± 26 %, percentage error 51 %). Reproducibility was high with 0.0 ± 0.3 l/min (bias 0 ± 8 %, percentage error 15 %). Outlier analysis revealed gender, height, CO and stroke volume (SV) by CMR as independent predictors for larger variation. Stratification of COCMR in quintiles demonstrated a good agreement for low values (<4.4 l/min) with bias increasing significantly with quintile as high as 3.1 ± 1.1 l/min (p < 0.001). Reproducibility was not affected (p = 0.71). Subgroup analysis in patients with arrhythmias (p = 0.19), changes in thoracic fluid content (p = 0.51) or left heart failure (p = 0.47) could not detect significant differences in accuracy. EV showed insufficient agreement with CMR and good reproducibility. Gender, height and increasing CO and SV were associated with increased bias while not affecting reproducibility. Therefore, absolute values should not be used interchangeably in clinical routine. EV yet may find its place for clinical application with further investigation on its trending ability pending. PMID:26115774

  17. 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

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

    PubMed

    Bouchard, Kristofer E; Conant, David F; 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

  19. Non-Invasive Imaging Serum Amyloid A Activation through the NF-κB Signal Pathway upon Gold Nanostructure Exposure.

    PubMed

    Zhang, Yulong; Zhou, Qianqian; Yan, Shaoduo; Zhang, Ning; Zhao, Man; Ma, Cong; He, Chulin; Fu, Qiuxia; Wu, Tao; Wang, Xiaohui; Zhan, Linsheng

    2016-06-01

    With the objective of investigating the acute activation of inflammatory cascades upon exposure to gold nanoparticles (GNPs) as well as detailing the mechanisms, a reporter mouse model that allows for non-invasive and longitudinal imaging of hepatic acute-phase serum amyloid A (SAA) activation is constructed. The model is able to visualize SAA activation at the transcriptional stage, with higher sensitivity than serum protein detection by ELISA. GNPs of various sizes (10-80 nm) and geometries are assessed using the reporter mice with results demonstrating that 50 nm nanospheres (GNS50) possess the highest capacity to induce hepatic SAA activation. Detailed analysis uncovers that resident macrophages in the liver are the main origins of these cytokines and that the exposure to GNS50 significantly induces the M1 macrophage phenotype. Moreover, those M1-polarized macrophages, together with the subsequently secreted pro-inflammatory cytokines, exert effects on hepatocytes and then initiate SAA transcription through the NF-κB signal pathway. The results detail the sequential reactions to GNPs among macrophages, inflammatory mediators, and SAA-synthesizing hepatocytes, which shed light on the acute effects of GNPs on the body. In addition, the established in situ and highly sensitive SAA detection system is expected to have vast applications in evaluating NP-induced acute inflammatory reactions. PMID:27167493

  20. 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.

  1. 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

  2. Non-invasive functional imaging of Cerebral Blood Volume with Vascular-Space-Occupancy (VASO) MRI

    PubMed Central

    Lu, Hanzhang; Hua, Jun; van Zijl, Peter C.M.

    2013-01-01

    Functional MRI (fMRI) based on changes in cerebral blood volume (CBV) can directly probe vasodilatation and vasoconstriction during brain activation or physiologic challenges, and can provide important insights into the mechanism of Blood-Oxygenation-Level-Dependent (BOLD) signal changes. At present, the most widely used CBV fMRI technique in humans is called Vascular-Space-Occupancy (VASO) MRI and this article provides a technical review of this method. VASO MRI utilizes T1 differences between blood and tissue to distinguish these two compartments within a voxel and uses blood-nulling inversion recovery sequence to yield an MR signal proportional to 1-CBV. As such, vasodilatation will result in a VASO signal decrease and vasoconstriction will have the reverse effect. The VASO technique can be performed dynamically with a temporal resolution comparable to several other fMRI methods such as BOLD or Arterial-Spin-Labeling (ASL), and is particularly powerful when conducted in conjunction with these complementary techniques. The pulse sequence and imaging parameters of VASO can be optimized such that the signal change is predominantly of CBV origin, but careful considerations should be taken to minimize other contributions, such as those from the BOLD effect, CBF, and CSF. Sensitivity of the VASO technique remains to be the primary disadvantage when compared to BOLD, but this technique is increasingly demonstrating utility in neuroscientific and clinical applications. PMID:23355392

  3. 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.

  4. Non-invasive Monitoring of Ultrasound-Stimulated Microbubble Radiation Enhancement Using Photoacoustic Imaging

    PubMed Central

    Briggs, Kaleigh; Al Mahrouki, Azza; Nofiele, Joris; El-Falou, Ahmad; Stanisz, Martin; Kim, Hyunjung Christina; Kolios, Michael C.; Czarnota, Gregory J.

    2014-01-01

    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. PMID:24000993

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

    NASA Astrophysics Data System (ADS)

    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-cyclo-dodecane-1,4,7-triacetate) was evaluated as a temperature-sensitive contrast agent using the temperature dependence (~0.12 ppm °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 °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 leq0.2 °C. Furthermore, 3D EPSI experiments with a 16 × 16 × 16 matrix size yielded temperature measurements within 17 s from voxels of size 3 × 3×3 mm3.

  6. Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique

    PubMed Central

    van Onna, M; Ten Cate, D F; Tsoi, K L; Meier, A J L; Jacobs, J W G; Westgeest, A A A; Meijer, P B L; van Beek, M C; Rensen, W H J; Bijlsma, J W J

    2016-01-01

    Objectives In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. Methods In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. Results At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. Conclusions In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA. PMID:26452538

  7. 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. PMID:26138371

  8. 1NON-INVASIVE RADIOIODINE IMAGING FOR ACCURATE QUANTITATION OF NIS REPORTER GENE EXPRESSION IN TRANSPLANTED HEARTS

    PubMed Central

    Ricci, Davide; Mennander, Ari A; Pham, Linh D; Rao, Vinay P; Miyagi, Naoto; Byrne, Guerard W; Russell, Stephen J; McGregor, Christopher GA

    2008-01-01

    Objectives We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 minutes prior to transplantation with University of Wisconsin (UW) solution (n=3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n=6), hNIS-hCEA (Ad-NIS-CEA; n=6) and hNIS-βhCG (Ad-NIS-CG; n=6). On post-operative day (POD) 5, 10, 15 all animals underwent micro-SPECT/CT imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1±0.2; 0.9±0.07), Ad-NIS-CEA (1.2±0.3; 0.9±0.1) and Ad-NIS-CG (1.1±0.1; 0.9±0.1) compared to UW group (0.44±0.03; 0.47±0.06) on POD 5 and 10 (p<0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2=0.99 and R2=0.96 respectively). Conclusions These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic single photon emission computed tomography (SPECT) imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5. PMID:17980613

  9. 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

  10. 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

  11. 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. PMID:23579949

  12. PET imaging to non-invasively study immune activation leading to antitumor responses with a 4-1BB agonistic antibody

    PubMed Central

    2013-01-01

    Background Molecular imaging with positron emission tomography (PET) may allow the non-invasive study of the pharmacodynamic effects of agonistic monoclonal antibodies (mAb) to 4-1BB (CD137). 4-1BB is a member of the tumor necrosis factor family expressed on activated T cells and other immune cells, and activating 4-1BB antibodies are being tested for the treatment of patients with advanced cancers. Methods We studied the antitumor activity of 4-1BB mAb therapy using [18 F]-labeled fluoro-2-deoxy-2-D-glucose ([18 F]FDG) microPET scanning in a mouse model of colon cancer. Results of microPET imaging were correlated with morphological changes in tumors, draining lymph nodes as well as cell subset uptake of the metabolic PET tracer in vitro. Results The administration of 4-1BB mAb to Balb/c mice induced reproducible CT26 tumor regressions and improved survival; complete tumor shrinkage was achieved in the majority of mice. There was markedly increased [18 F]FDG signal at the tumor site and draining lymph nodes. In a metabolic probe in vitro uptake assay, there was an 8-fold increase in uptake of [3H]DDG in leukocytes extracted from tumors and draining lymph nodes of mice treated with 4-1BB mAb compared to untreated mice, supporting the in vivo PET data. Conclusion Increased uptake of [18 F]FDG by PET scans visualizes 4-1BB agonistic antibody-induced antitumor immune responses and can be used as a pharmacodynamic readout to guide the development of this class of antibodies in the clinic. PMID:24829750

  13. Molecular imaging in ovarian cancer.

    PubMed

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  14. 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. PMID:26186005

  15. 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.

  16. 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. PMID:27299677

  17. Non-Invasive Drosophila ECG Recording by Using Eutectic Gallium-Indium Alloy Electrode: A Feasible Tool for Future Research on the Molecular Mechanisms Involved in Cardiac Arrhythmia

    PubMed Central

    Kuo, Po-Hung; Tzeng, Te-Hsuen; Huang, Yi-Chun; Chen, Yu-Hao; Chang, Yi-Chung; Ho, Yi-Lwun; Wu, June-Tai; Lee, Hsiu-Hsian; Lai, Po-Jung; Liu, Kwei-Yan; Cheng, Ya-Chen; Lu, Shey-Shi

    2014-01-01

    Background Drosophila heart tube is a feasible model for cardiac physiological research. However, obtaining Drosophila electrocardiograms (ECGs) is difficult, due to the weak signals and limited contact area to apply electrodes. This paper presents a non-invasive Gallium-Indium (GaIn) based recording system for Drosophila ECG measurement, providing the heart rate and heartbeat features to be observed. This novel, high-signal-quality system prolongs the recording time of insect ECGs, and provides a feasible platform for research on the molecular mechanisms involved in cardiovascular diseases. Methods In this study, two types of electrode, tungsten needle probes and GaIn electrodes, were used respectively to noiselessly conduct invasive and noninvasive ECG recordings of Drosophila. To further analyze electrode properties, circuit models were established and simulated. By using electromagnetic shielded heart signal acquiring system, consisted of analog amplification and digital filtering, the ECG signals of three phenotypes that have different heart functions were recorded without dissection. Results and Discussion The ECG waveforms of different phenotypes of Drosophila recorded invasively and repeatedly with n value (n>5) performed obvious difference in heart rate. In long period ECG recordings, non-invasive method implemented by GaIn electrodes acts relatively stable in both amplitude and period. To analyze GaIn electrode, the correctness of GaIn electrode model established by this paper was validated, presenting accuracy, stability, and reliability. Conclusions Noninvasive ECG recording by GaIn electrodes was presented for recording Drosophila pupae ECG signals within a limited contact area and signal strength. Thus, the observation of ECG changes in normal and SERCA-depleted Drosophila over an extended period is feasible. This method prolongs insect survival time while conserving major ECG features, and provides a platform for electrophysiological signal research

  18. Non-Invasive In Vivo Imaging of Near Infrared-labeled Transferrin in Breast Cancer Cells and Tumors Using Fluorescence Lifetime FRET

    PubMed Central

    Periasamy, Ammasi; Intes, Xavier; Barroso, Margarida

    2013-01-01

    The conjugation of anti-cancer drugs to endogenous ligands has proven to be an effective strategy to enhance their pharmacological selectivity and delivery towards neoplasic tissues. Since cell proliferation has a strong requirement for iron, cancer cells express high levels of transferrin receptors (TfnR), making its ligand, transferrin (Tfn), of great interest as a delivery agent for therapeutics. However, a critical gap exists in the ability to non-invasively determine whether drugs conjugated to Tfn are internalized into target cells in vivo. Due to the enhanced permeability and retention (EPR) effect, it remains unknown whether these Tfn-conjugated drugs are specifically internalized into cancer cells or are localized non-specifically as a result of a generalized accumulation of macromolecules near tumors. By exploiting the dimeric nature of the TfnR that binds two molecules of Tfn in close proximity, we utilized a Förster Resonance Energy Transfer (FRET) based technique that can discriminate bound and internalized Tfn from free, soluble Tfn. In order to non-invasively visualize intracellular amounts of Tfn in tumors through live animal tissues, we developed a novel near infrared (NIR) fluorescence lifetime FRET imaging technique that uses an active wide-field time gated illumination platform. In summary, we report that the NIR fluorescence lifetime FRET technique is capable of non-invasively detecting bound and internalized forms of Tfn in cancer cells and tumors within a live small animal model, and that our results are quantitatively consistent when compared to well-established intensity-based FRET microscopy methods used in in vitro experiments. PMID:24278268

  19. A simple one-step method to prepare fluorescent carbon dots and their potential application in non-invasive glioma imaging

    NASA Astrophysics Data System (ADS)

    Ruan, Shaobo; Qian, Jun; Shen, Shun; Zhu, Jianhua; Jiang, Xinguo; He, Qin; Gao, Huile

    2014-08-01

    Fluorescent carbon dots (CD) possess impressive potential in bioimaging because of their low photobleaching, absence of optical blinking and good biocompatibility. However, their relatively short excitation/emission wavelengths restrict their application in in vivo imaging. In the present study, a kind of CD was prepared by a simple heat treatment method using glycine as the only precursor. The diameter of CD was lower than 5 nm, and the highest emission wavelength was 500 nm. However, at 600 nm, there was still a relatively strong fluorescent emission, suggesting CD could be used for in vivo imaging. Additionally, several experiments demonstrated that CD possessed good serum stability and low cytotoxicity. In vitro, CD could be taken up into C6 glioma cells in a time- and concentration-dependent manner, with both endosomes and mitochondria involved. In vivo, CD could be used for non-invasive glioma imaging because of its high accumulation in the glioma site of the brain, which was demonstrated by both in vivo imaging and ex vivo tissue imaging. Furthermore, the fluorescent distribution in tissue slices also showed CD distributed in glioma with high intensity, while with a low intensity in normal brain tissue. In conclusion, CD were prepared using a simple method with relatively long excitation and emission wavelengths and could be used for non-invasive glioma imaging.Fluorescent carbon dots (CD) possess impressive potential in bioimaging because of their low photobleaching, absence of optical blinking and good biocompatibility. However, their relatively short excitation/emission wavelengths restrict their application in in vivo imaging. In the present study, a kind of CD was prepared by a simple heat treatment method using glycine as the only precursor. The diameter of CD was lower than 5 nm, and the highest emission wavelength was 500 nm. However, at 600 nm, there was still a relatively strong fluorescent emission, suggesting CD could be used for in vivo imaging

  20. Image quality and diagnostic accuracy of non-invasive coronary imaging with 16 detector slice spiral computed tomography with 188 ms temporal resolution

    PubMed Central

    Kuettner, A; Beck, T; Drosch, T; Kettering, K; Heuschmid, M; Burgstahler, C; Claussen, C D; Kopp, A F; Schroeder, S

    2005-01-01

    Objective: To evaluate image quality and clinical accuracy in detecting coronary artery lesions with a new multidetector spiral computed tomography (MDCT) generation with 16 detector slices and a temporal resolution of 188 ms. Methods: 124 consecutive patients scheduled for invasive coronary angiography (ICA) were additionally studied by MDCT (Sensation 16 Speed 4D). MDCTs were analysed with regard to image quality and presence of coronary artery lesions. The results were compared with ICA. Results: 120 of 124 scans were successful. The image quality of all remaining 120 scans was sufficient (mean (SD) heart rate 64.2 (9.8) beats/min, range 43–95). The mean calcium mass was 167 (223) mg (range 0–1038). Thirteen coronary segments were evaluated for each patient (1560 segments in total). Image quality was graded as follows: excellent, 422 (27.1%) segments; good, 540 (34.6%) segments; moderate, 277 (17.7%) segments; heavily calcified, 215 (13.8%) segments; and blurred, 106 (6.8%) segments. ICA detected 359 lesions with a diameter stenosis > 50% and MDCT detected 304 of 359 (85%). Sensitivity, specificity, and positive and negative predictive values were 85%, 98%, 91%, and 96%, respectively. The correct clinical diagnosis (presence or absence of at least one stenosis > 50%) was obtained for 110 of 120 (92%) patients. Conclusions: MDCT image quality can be further improved with 16 slices and faster gantry rotation time. These results in an unselected population underline the potential of MDCT to become a non-invasive diagnostic alternative, especially for the exclusion of coronary artery disease, in the near future. PMID:15958366

  1. 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.

  2. Establishment of a Non-Invasive Semi-Quantitative Bioluminescent Imaging Method for Monitoring of an Orthotopic Esophageal Cancer Mouse Model

    PubMed Central

    Kuroda, Shinji; Kubota, Tetsushi; Aoyama, Katsuyuki; Kikuchi, Satoru; Tazawa, Hiroshi; Nishizaki, Masahiko; Kagawa, Shunsuke; Fujiwara, Toshiyoshi

    2014-01-01

    Orthotopic models of various types of tumors are widely used in anti-tumor therapeutic experiments in preclinical studies. However, there are few ways to appropriately monitor therapeutic effect in orthotopic tumor models, especially for tumors invisible from the outside. In this study we aimed to establish a non-invasive semi-quantitative bioluminescent imaging method of monitoring an orthotopic esophageal cancer mouse model. We confirmed that the TE8 esophageal cancer cell line implanted orthotopically into the abdominal esophagus of nu/nu mice (n = 5) developed not only a main tumor at the implanted site, but also local lymph node metastases and peritoneal disseminations within 6 weeks after inoculation. We established a TE8 cell line that stably expressed the firefly luciferase gene (TE8-Luc). We showed that TE8-Luc cells implanted subcutaneously into nu/nu mice (n = 5) grew over time until 5 weeks after inoculation. Tumor volume was strongly correlated with luminescent intensity emitted from the tumor, which was quantified using the IVIS imaging system. We then showed that TE8-Luc cells implanted orthotopically into the mouse abdominal esophagus (n = 8) also formed a tumor and that the luminescent intensity of such a tumor, as detected by IVIS, increased over time until 7 weeks after inoculation and was therefore likely to reflect tumor progression. We therefore propose that this orthotopic esophageal cancer model, monitored using the non-invasive semi-quantitative IVIS imaging system, will be useful for in vivo therapeutic experiments against esophageal cancer. This experimental setting is expected to contribute to the development of novel therapeutic technologies for esophageal cancer in preclinical studies. PMID:25493557

  3. 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. PMID:20506297

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

    PubMed Central

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

    2016-01-01

    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. PMID:27231625

  5. Liver glycogen storage diseases due to phosphorylase system deficiencies: diagnosis thanks to non invasive blood enzymatic and molecular studies.

    PubMed

    Davit-Spraul, Anne; Piraud, Monique; Dobbelaere, Dries; Valayannopoulos, Vassili; Labrune, Philippe; Habes, Dalila; Bernard, Olivier; Jacquemin, Emmanuel; Baussan, Christiane

    2011-01-01

    Glycogen storage disease (GSD) due to a deficient hepatic phosphorylase system defines a genetically heterogeneous group of disorders that mainly manifests in children. We investigated 45 unrelated children in whom a liver GSD VI or IX was suspected on the basis of clinical symptoms including hepatomegaly, increased serum transaminases, postprandial lactatemia and/or mild fasting hypoglycemia. Liver phosphorylase and phosphorylase b kinase activities studied in peripheral blood cells allowed to suspect diagnosis in 37 cases but was uninformative in 5. Sequencing of liver phosphorylase genes was useful to establish an accurate diagnosis. Causative mutations were found either in the PYGL (11 patients), PHKA2 (26 patients), PHKG2 (three patients) or in the PHKB (three patients) genes. Eleven novel disease causative mutations, five missense (p.N188K, p.D228Y, p.P382L, p.R491H, p.L500R) and six truncating mutations (c.501_502ins361pb, c.528+2T>C, c.856-29_c.1518+614del, c.1620+1G>C, p.E703del and c.2313-1G>T) were identified in the PYGL gene. Seventeen novel disease causative mutations, ten missense (p.A42P, p.Q95R, p.G131D, p.G131V, p.Q134R, p.G187R, p.G300V, p.G300A, p.C326Y, p.W820G) and seven truncating (c.537+5G>A, p.G396DfsX28, p.Q404X, p.N653X, p.L855PfsX87, and two large deletions) were identified in the PHKA2 gene. Four novel truncating mutations (p.R168X, p.Q287X, p.I268PfsX12 and c.272-1G>C) were identified in the PHKG2 gene and three (c.573_577del, p.R364X, c.2427+3A>G) in the PHKB gene. Patients with PHKG2 mutations evolved towards cirrhosis. Molecular analysis of GSD VI or IX genes allows to confirm diagnosis suspected on the basis of enzymatic analysis and to establish diagnosis and avoid liver biopsy when enzymatic studies are not informative in blood cells. PMID:21646031

  6. Targeted Non-invasive Imaging of EGFR-expressing Orthotopic Pancreatic Cancer using Multispectral Optoacoustic Tomography (MSOT)

    PubMed Central

    Hudson, Shanice V.; Huang, Justin S.; Yin, Wenyuan; Albeituni, Sabrin; Rush, Jamie; Khanal, Anil; Yan, Jun; Ceresa, Brian P.; Frieboes, Hermann B.; McNally, Lacey R.

    2014-01-01

    Detection of orthotopic xenograft tumors is difficult due to poor spatial resolution and reduced image fidelity with traditional optical imaging modalities. In particular, light scattering and attenuation in tissue at depths beyond subcutaneous implantation hinder adequate visualization. We evaluate the use of multispectral optoacoustic tomography (MSOT) to detect upregulated epidermal growth factor (EGF) receptor in orthotopic pancreatic xenografts using a near-infrared (NIR) EGF-conjugated CF-750 fluorescent probe. MSOT is based on the photoacoustic effect and thus not limited by photon scattering, resulting in high-resolution tomographic images. Pancreatic tumor-bearing mice with luciferase-transduced S2VP10L tumors were intravenously injected with EGF-750 probe prior to MSOT imaging. We characterized probe specificity and bioactivity via immunoblotting, immunocytochemistry, and flow cytometric analysis. In vitro data along with optical bioluminescence/fluorescence imaging were used to validate acquired MSOT in vivo images of probe biodistribution. Indocyanine green dye was used as a non-specific control to define specificity of EGF-probe accumulation. Maximum accumulation occurred at six hours post-injection, demonstrating specific intra-tumoral probe uptake and minimal liver and kidney off-target accumulation. Optical bioluminescence and fluorescence imaging confirmed tumor-specific probe accumulation consistent with MSOT images. These studies demonstrate the utility of MSOT to obtain volumetric images of ligand probe biodistribution in vivo to detect orthotopic pancreatic tumor lesions through active targeting of EGF receptor. PMID:25217521

  7. 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

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

    PubMed

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

    2015-01-01

    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

  9. 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

  10. 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

  11. 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.

  12. Combination of Autofluorescence imaging and salivary protoporphyrin in Oral precancerous and cancerous lesions: Non-invasive tools

    PubMed Central

    Jacobs, Reinhilde

    2015-01-01

    Background Normal and cancerous tissues have distinct auto-fluorescence properties because of differences in their biophysical and biochemical agents. Scientific evidences related to diagnostic fluorescence imaging for detection of oral precancerous and cancerous lesions are very limited. Objectives The aim of this study was to find out potential relationships between serum, salivary and tissue protoporphyrin IX ( PX) levels in subjects with or without oral precancerous and cancerous lesions. Also , to find out diagnostic value of fluorescence imaging (VELscope® system , LED Dental Inc., White Rock, B.C.) and salivary protoporphyrin IX (PX) in oral precancerous and cancerous lesions. Furthermore this study attempts to find out diagnostic value of the combination of approaches of fluorescence imaging and salivary protoporphyrin for detection of oral precancerous and cancerous lesions. Material and Methods The study sample comprised 3 test groups, with biopsy confirmed precancerous (leukoplakia and lichen planus) and cancerous lesions (squamous cell carcinoma) and one control group of 25 healthy individuals. To find out sensitivity and specificity, another 100 patients presenting for routine dental care were selected and clinical examinations were followed by fluorescence imaging and normal photography, which were finally confirmed by biopsy. The clinical and histopathogical examinations were done in conjunction with photography of the oral cavity using digital camera and fluorescence imaging. Serum, tissue and salivary protoporphyrin (PX) levels were measured. Results Using fluorescence imaging, oral cancerous and precancerous lesions showed deep purple to deep brown and dark green colour respectively, while normal tissues showed pale green colour in contrast. The PX levels in serum, salivary and tissues were significantly higher in precancerous and cancerous lesions as compared to normal healthy tissues. Salivary and serum PX levels were highly correlated in all

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

    PubMed

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

    2016-08-01

    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

  14. 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.

  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. PMID:21517815

  16. Non-invasive quantitative micro-PIXE-RBS/EBS/EBS imaging reveals the lost polychromy and gilding of the Neo-Assyrian ivories from the Louvre collection.

    PubMed

    Albéric, Marie; Müller, Katharina; Pichon, Laurent; Lemasson, Quentin; Moignard, Brice; Pacheco, Claire; Fontan, Elisabeth; Reiche, Ina

    2015-05-01

    Antique objects are known to have been brightly colored. However, the appearance of these objects has changed over time and paint traces are rarely preserved. The surface of ivory objects (8th century B.C., Syria) from the Louvre museum collection (Paris) have been non-invasively studied by simultaneous particle-induced X-ray emission (PIXE) and Rutherford and elastic backscattering spectrometry (RBS/EBS) micro-imaging at the AGLAE facility (C2RMF, Paris). Qualitative 2D chemical images of elements ranging from Na to Pb on the surface of the ancient ivory carvings provide evidence of lost polychromy and gilding. Quantitative PIXE data of specific areas allow discrimination between traces of sediments and former polychromy. Different shades of blue can be differentiated from particular Pb/Cu ratios. The characterization of gilding based on RBS data demonstrates the exceptional technological skills of the Phoenician craftsmen supposed to have carved the Arslan Tash ivories. More precise reconstructions of the original polychromy compared to previous studies and a criterion for the authentication of ancient gilded ivory object are proposed. PMID:25770612

  17. Molecular imaging in atherosclerosis

    PubMed Central

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

    2010-01-01

    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

  18. Non-Invasive imaging of small-animal tumors: high-frequency ultrasound vs. MicroPET.

    PubMed

    Liao, Ai-Ho; Li, Chen-Han; Cheng, Weng-Fang; Li, Pai-Chi

    2005-01-01

    Tumor volume measurement on small animals is important but currently invasive. We employ ultrasonic micro-imaging (UMI) in this study and demonstrate its feasibility. In addition, we use small animal positron emission tomography (microPET) as a preliminary effort to develop multi-modality small animal imaging techniques. The tumor growth curve from UMI is also compared to radioactivity from microPET. Both UMI and [18F] FDG microPET imaging were performed on C57BL/6J black mice bearing WF-3 ovary cancer cells at various stages from the second week till up to the eighth week. Segmentation and 3D reconstruction were also done. The growth curve was obtained in vivo noninvasively by UMI. The cell doubling time was 7.46 days according to UMI. This result was compared with vernier caliper measurement and radioactivity counting by microPET. In microPET, we obtained the time-activity curves from the tumor and the tumor-surrounding tissue. The tumor-to-normal-tissues ratios reached maximum at the fifth week after tumor cell implantation. PMID:17281549

  19. 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.

  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. PMID:23764946

  1. 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

  2. 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.

  3. 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

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

    PubMed

    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 Mn(2+) 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 Mn(2+) ions. Binding to proteins increases the relaxivity of Mn(2+) 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. PMID:27183055

  5. Chitosan derivatives cross-linked with iodinated 2,5-dimethoxy-2,5-dihydrofuran for non-invasive imaging.

    PubMed

    Ghosh, Paulomi; Das, Manisit; Rameshbabu, Arun Prabhu; Das, Dipankar; Datta, Sayanti; Pal, Sagar; Panda, Asit Baran; Dhara, Santanu

    2014-10-22

    Radiopaque polymer derivatives were successfully prepared through surface diffusion mediated cross-linking of chitosan with iodinated 2,5-dimethoxy-2,5-dihydrofuran. The incorporation of iodine in 2,5-dimethoxy-2,5-dihydrofuran was validated by (1)H NMR and mass spectroscopy. The cross-linking of the glucosamine moieties of chitosan with the iodinated product was confirmed by (13)C NMR and energy-dispersive X-ray spectroscopy. Radiography analysis proved inherent opacity of the iodinated fibrous sheets and microspheres that were comparable to the X-ray visibility of aluminum hollow rings of equivalent thickness and commercially available radiopaque tape, respectively. Microscopic studies evidenced retention of the fiber/microsphere morphology after the iodination/cross-linking reactions. The effects of iodination/cross-linking on the mechanical and biodegradation properties of fibers were studied by nanoindentation and enzymatic assay, respectively. In vitro and in vivo studies established the nontoxic, biodegradable nature of radiopaque derivatives. Iodinated fiber mesh implanted in a rabbit model was significantly X-ray opaque compared to the uncross-linked fiber mesh and medical grade surgical swabs. Further, opacity of the iodinated mesh was evident even after 60 days, though the intensity was reduced, which indicates the biodegradable nature of the iodinated polymer. The opacity of the iodinated sutures was also established in the computed tomography images. Finally, the sufficient in vivo contrast property of the radiopaque microspheres in the gastrointestinal tract indicates its possible role in clinical diagnostics. PMID:25265599

  6. 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.

  7. 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

  8. Non-invasive evaluation of neuroprotective drug candidates for cerebral infarction by PET imaging of mitochondrial complex-I activity.

    PubMed

    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-(18)F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([(18)F]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, [(18)F]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 [(18)F]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 [(18)F]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 [(18)F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain. PMID:27440054

  9. 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

  10. 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

  11. 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

  12. Monitor Therapeutic Response of Human Ovarian Cancer to 17-DMAG by Non-invasive PET imaging with 64Cu-DOTA-Trastuzumab

    PubMed Central

    Niu, Gang; Li, Zibo; Cao, Qizhen; Chen, Xiaoyuan

    2012-01-01

    Purposes 17-DMAG, a heat shock protein 90 (Hsp90) inhibitor, has been intensively investigated for cancer therapy and is undergoing clinical trials. Human epidermal growth factor receptor 2 (HER-2) is one of the client proteins of Hsp90 and its expression is decreased upon 17-DMAG treatment. In this study, we aimed to non-invasively monitor the HER-2 response to 17-DMAG treatment in xenografted mice. Methods The sensitivity of human ovarian cancer SKOV-3 cells to 17-DMAG in vitro was measured by MTT assay. HER-2 expression of SKOV-3 cells was determined by flow cytometry. Nude mice bearing SKOV-3 tumors were treated with 17-DMAG and the therapeutic efficacy was evaluated by tumor size measurement. Both treated and control mice were imaged with microPET using 64Cu-DOTA-trastuzumab and 18F-FDG. Biodistribution studies, immunofluorescence staining were performed to validate the microPET results. Results SKOV-3 cells are sensitive to 17-DMAG treatment, in a dose dependent manner, with an IC50 value of 68.7 nM after 72 h incubation. The tumor growth curve supported the inhibition effect of 17-DMAG on SKOV-3 tumors. Quantitative microPET imaging showed that 64Cu-DOTA-trastuzumab had prominent tumor activity accumulation in untreated SKOV-3 tumors, which was significantly reduced in 17-DMAG treated tumors. There was no uptake difference detected by FDG PET. Immunofluorescence staining confirmed the significant reduction in tumor HER-2 level upon 17-DMAG treatment. Conclusion The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using 64Cu-DOTA-trastuzumab. This approach may be valuable in monitoring the therapeutic response in HER-2-positive cancer patients under 17-DMAG treatment. PMID:19440708

  13. 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.

  14. 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

  15. 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.

  16. The roadmap for estimation of cell-type-specific neuronal activity from non-invasive measurements.

    PubMed

    Uhlirova, Hana; Kılıç, Kıvılcım; Tian, Peifang; Sakadžić, Sava; Gagnon, Louis; Thunemann, Martin; Desjardins, Michèle; Saisan, Payam A; Nizar, Krystal; Yaseen, Mohammad A; Hagler, Donald J; Vandenberghe, Matthieu; Djurovic, Srdjan; Andreassen, Ole A; Silva, Gabriel A; Masliah, Eliezer; Kleinfeld, David; Vinogradov, Sergei; Buxton, Richard B; Einevoll, Gaute T; Boas, David A; Dale, Anders M; Devor, Anna

    2016-10-01

    The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use non-invasive technologies. This is in contrast to animal models where a rich, detailed view of cellular-level brain function with cell-type-specific molecular identity has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from non-invasive signals in humans. On the essential path towards this goal is the development of a detailed 'bottom-up' forward model bridging neuronal activity at the level of cell-type-specific populations to non-invasive imaging signals. The general idea is that specific neuronal cell types have identifiable signatures in the way they drive changes in cerebral blood flow, cerebral metabolic rate of O2 (measurable with quantitative functional Magnetic Resonance Imaging), and electrical currents/potentials (measurable with magneto/electroencephalography). This forward model would then provide the 'ground truth' for the development of new tools for tackling the inverse problem-estimation of neuronal activity from multimodal non-invasive imaging data.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574309

  17. 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.

  18. 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 PAGESBeta

    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 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

  19. 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.

  20. Non-invasive characterization of polyurethane-based tissue constructs in a rat abdominal repair model using high frequency ultrasound elasticity imaging.

    PubMed

    Yu, Jiao; Takanari, Keisuke; Hong, Yi; Lee, Kee-Won; Amoroso, Nicholas J; Wang, Yadong; Wagner, William R; Kim, Kang

    2013-04-01

    The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice. PMID:23347836

  1. 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

  2. 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. PMID:25767612

  3. Non-invasive Characterization of Polyurethane-based Tissue Constructs in a Rat Abdominal Repair Model Using High Frequency Ultrasound Elasticity Imaging

    PubMed Central

    Yu, Jiao; Takanari, Keisuke; Hong, Yi; Lee, Kee-Won; Amoroso, Nicholas J.; Wang, Yadong; Wagner, William R.; Kim, Kang

    2013-01-01

    The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice. PMID:23347836

  4. Non-invasive Mapping of Cardiac Arrhythmias.

    PubMed

    Shah, Ashok; Hocini, Meleze; Haissaguerre, Michel; Jaïs, Pierre

    2015-08-01

    Since more than 100 years, 12-lead electrocardiography (ECG) is the standard-of-care tool, which involves measuring electrical potentials from limited sites on the body surface to diagnose cardiac disorder, its possible mechanism, and the likely site of origin. Several decades of research has led to the development of a 252-lead ECG and computed tomography (CT) scan-based three-dimensional electro-imaging modality to non-invasively map abnormal cardiac rhythms including fibrillation. These maps provide guidance towards ablative therapy and thereby help advance the management of complex heart rhythm disorders. Here, we describe the clinical experience obtained using non-invasive technique in mapping the electrical disorder and guide the catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats), and ventricular pre-excitation (Wolff-Parkinson-White syndrome). PMID:26072438

  5. [Non-invasive assessment of fatty liver].

    PubMed

    Egresi, Anna; Lengyel, Gabriella; Hagymási, Krisztina

    2015-04-01

    As the result of various harmful effects (infectious agents, metabolic diseases, unhealthy diet, obesity, toxic agents, autoimmune processes) hepatic damage may develop, which can progress towards liver steatosis, and fibrosis as well. The most common etiological factors of liver damages are hepatitis B and C infection, alcohol consumption and non-alcoholic fatty liver disease. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Due to the dangers and complications of liver biopsy, studies are focused on non-invasive markers and radiological imaging for liver steatosis, progression of fatty liver, activity of the necroinflammation and the severity of the fibrosis. Authors review the possibilities of non-invasive assessment of liver steatosis. The statistical features of the probes (positive, negative predictive values, sensitivity, specificity) are reviewed. The role of radiological imaging is also discussed. Although the non-invasive methods discussed in this article are useful to assess liver steatosis, further studies are needed to validate to follow progression of the diseases and to control therapeutic response. PMID:25819147

  6. Quantitative parameters to compare image quality of non-invasive coronary angiography with 16-slice, 64-slice and dual-source computed tomography.

    PubMed

    Burgstahler, Christof; Reimann, Anja; Brodoefel, Harald; Daferner, Ulrike; Herberts, Tina; Tsiflikas, Ilias; Thomas, Christoph; Drosch, Tanja; Schroeder, Stephen; Heuschmid, Martin

    2009-03-01

    Multi-slice computed tomography (MSCT) is a non-invasive modality to visualize coronary arteries with an overall good image quality. Improved spatial and temporal resolution of 64-slice and dual-source computed tomography (DSCT) scanners are supposed to have a positive impact on diagnostic accuracy and image quality. However, quantitative parameters to compare image quality of 16-slice, 64-slice MSCT and DSCT are missing. A total of 256 CT examinations were evaluated (Siemens, Sensation 16: n = 90; Siemens Sensation 64: n = 91; Siemens Definition: n = 75). Mean Hounsfield units (HU) were measured in the cavum of the left ventricle (LV), the ascending aorta (Ao), the left ventricular myocardium (My) and the proximal part of the left main (LM), the left anterior descending artery (LAD), the right coronary artery (RCA) and the circumflex artery (CX). Moreover, the ratio of intraluminal attenuation (HU) to myocardial attenuation was assessed for all coronary arteries. Clinical data [body mass index (BMI), gender, heart rate] were accessible for all patients. Mean attenuation (CA) of the coronary arteries was significantly higher for DSCT in comparison to 64- and 16-slice MSCT within the RCA [347 +/- 13 vs. 254 +/- 14 (64-MSCT) vs. 233 +/- 11 (16-MSCT) HU], LM (362 +/- 11/275 +/- 12/262 +/- 9), LAD (332 +/- 17/248 +/- 19/219 +/- 14) and LCX (310 +/- 12/210 +/- 13/221 +/- 10, all p < 0.05), whereas there was no significant difference between DSCT and 64-MSCT for the LV, the Ao and My. Heart rate had a significant impact on CA ratio in 16-slice and 64-slice CT only (p < 0.05). BMI had no impact on the CA ratio in DSCT only (p < 0.001). Improved spatial and temporal resolution of dual-source CT is associated with better opacification of the coronary arteries and a better contrast with the myocardium, which is independent of heart rate. In comparison to MSCT, opacification of the coronary arteries at DSCT is not affected by BMI. The main advantage of DSCT lies with the

  7. 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.

  8. Non-invasive physiological measurements

    SciTech Connect

    Rolfe, P.

    1983-01-01

    This book discusses the diagnostic techniques of nondestructive type for monitoring the physiology of various organ systems. The topics covered are: non-invasive assessment of gastric activity; uterine activity, intestinal activity; monitoring of fetal cardiovascular system and bilirubin physiology of infants. Respiratory system of infants is monitored and ultrasonography of heart is discussed.

  9. 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. PMID:25743562

  10. 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

  11. Molecular Imaging with Theranostic Nanoparticles

    PubMed Central

    Jokerst, Jesse V.; Gambhir, Sanjiv S.

    2011-01-01

    Conspectus Nanoparticles offer diagnostic and therapeutic capabilities impossible with small molecules or micro-scale tools. As molecular biology merges with medical imaging to form the field of molecular imaging, nanoparticle imaging is increasingly common with both therapeutic and diagnostic applications. The term theranostic indicates technology with concurrent and complementary diagnostic and therapeutic capabilities. When performed with sub-micron materials, the field may be termed theranostic nanomedicine. Although nanoparticles have been FDA-approved for clinical use as transport vehicles for nearly 15 years, full translation of their theranostic potential is incomplete. Still, remarkable successes with nanoparticles have been realized in the areas of drug delivery and magnetic resonance imaging. Emerging applications include image-guided resection, optical/photoacoustic imaging in vivo, contrast-enhanced ultrasound, and thermoablative therapy. Diagnosis with nanoparticles in molecular imaging involves correlating signal to a phenotype. The disease’s size, stage, and biochemical signature can be gleaned from the location and intensity of nanoparticle signal emanating from a living subject. Therapy with NP uses the image for resection or delivery of small molecule or RNA thererapeutic. Ablation of the affected area is also possible via heat or radioactivity. The ideal theranostic NP: (1) selectively and rapidly accumulates in diseased tissue, (2) reports biochemical and morphological characteristics of the area, (3) delivers a non-invasive therapeutic, and (4) is safe and biodegrades with non-toxic byproducts. Above is a schematic of such a system which contains a central imaging core (yellow) surrounded by small molecule therapeutics (red). The system targets via ligands such as IgG (pink) and is protected from immune scavengers by a cloak of protective polymer (green). While no nanoparticle has achieved all of the above features, many NPs do fulfill one

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. Strategies for non-invasive delivery of biologics.

    PubMed

    Chung, Seung Woo; Hil-lal, Taslim A; Byun, Youngro

    2012-07-01

    Macromolecular therapeutics, in particular, many biologics, is the most advancing category of drugs over conventional chemical drugs. The potency and specificity of the biologics for curing certain disease made them to be a leading compound in the pharmaceutical industry. However, due to their intrinsic nature, including high molecular weight, hydrophilicity and instability, they are difficult to be administered via non-invasive route. This is a major quest especially in biologics, as they are frequently used clinically for chronic disorders, which requires long-term administration. Therefore, many efforts have been made to develop formulation for non-invasive administration, in attempt to improve patient compliance and convenience. In this review, strategies for non-invasive delivery, in particular, oral, pulmonary and nasal delivery, that are recently adopted for delivery of biologics are discussed. Insulin, calcitonin and heparin were mainly focused for the discussion as they could represent protein, polypeptide and polysaccharide drugs, respectively. Many recent attempts for non-invasive delivery of biologics are compared to provide an insight of developing successful delivery system. PMID:22632037

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Non-invasive sensing for food reassurance.

    PubMed

    Xiaobo, Zou; Xiaowei, Huang; Povey, Malcolm

    2016-03-01

    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. PMID:26835653

  6. Non-Invasive Neuromodulation for Headache Disorders.

    PubMed

    Zhu, Shuhan; Marmura, Michael J

    2016-02-01

    Migraine and other chronic headache disorders are common and if inadequately treated, can lead to significant disability. The effectiveness of medications can be limited by side effects, drug interactions, and comorbid diseases necessitating alternative methods. Technological developments in the past 5 years have made it possible to use non-invasive methods of neuromodulation to treat primary headache disorders. This field includes technologies such as supraorbital transcutaneous stimulation (STS), transcranial magnetic stimulation (TMS), and non-invasive vagal nerve stimulation (nVNS). Existing trials show these modalities are safe and well tolerated and can be combined with standard pharmacotherapy. We review the technologies, biological rationales, and trials involving non-invasive neuromodulation for the treatment of primary headache disorders. PMID:26750126

  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. PMID:27548263

  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. 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

  10. Non-invasive Intratracheal Instillation in Mice

    PubMed Central

    Ortiz-Muñoz, Guadalupe; Looney, Mark R.

    2016-01-01

    The intratracheal instillation technique is used to deliver a variety of agents to the lungs ranging from pathogens (bacteria, viruses), toxins, to therapeutic agents. To model lung inflammation and injury, LPS can be administrated via intranasal, intratracheal, or aerosol approaches. Each technique has its limitations. The intratracheal technique can involve the non-invasive instillation method (via the oro-tracheal route) or a direct injection into the trachea. Here, we describe an optimized method for direct visual instillation of LPS via the non-invasive oro-tracheal route.

  11. 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)

  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. 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. PMID:27589232

  14. 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

  15. Non-invasive assessment of intracranial pressure.

    PubMed

    Robba, C; Bacigaluppi, S; Cardim, D; Donnelly, J; Bertuccio, A; Czosnyka, M

    2016-07-01

    Monitoring of intracranial pressure (ICP) is invaluable in the management of neurosurgical and neurological critically ill patients. Invasive measurement of ventricular or parenchymal pressure is considered the gold standard for accurate measurement of ICP but is not always possible due to certain risks. Therefore, the availability of accurate methods to non-invasively estimate ICP has the potential to improve the management of these vulnerable patients. This review provides a comparative description of different methods for non-invasive ICP measurement. Current methods are based on changes associated with increased ICP, both morphological (assessed with magnetic resonance, computed tomography, ultrasound, and fundoscopy) and physiological (assessed with transcranial and ophthalmic Doppler, tympanometry, near-infrared spectroscopy, electroencephalography, visual-evoked potentials, and otoacoustic emissions assessment). At present, none of the non-invasive techniques alone seem suitable as a substitute for invasive monitoring. However, following the present analysis and considerations upon each technique, we propose a possible flowchart based on the combination of non-invasive techniques including those characterizing morphologic changes (e.g., repetitive US measurements of ONSD) and those characterizing physiological changes (e.g., continuous TCD). Such an integrated approach, which still needs to be validated in clinical practice, could aid in deciding whether to place an invasive monitor, or how to titrate therapy when invasive ICP measurement is contraindicated or unavailable. PMID:26515159

  16. 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. PMID:27397413

  17. [Pulmonary non invasive infection by Scedosporium apiospermum].

    PubMed

    Cruz, Rodrigo; Barros, Manuel; Reyes, Mirtha

    2015-08-01

    We reported a case of non-invasive pulmonary infection by Scedosporium apiospermum in 67 years old female with bronchiectasis and caverns secondary to tuberculosis. Diagnosis was made with lung CT and bronchial lavage cultures. The patient was initially treated with itraconazole for six weeks without success and then voriconazole for 16 weeks, with good clinical response. PMID:26436797

  18. Cellular phone enabled non-invasive tissue classifier.

    PubMed

    Laufer, Shlomi; Rubinsky, Boris

    2009-01-01

    Cellular phone technology is emerging as an important tool in the effort to provide advanced medical care to the majority of the world population currently without access to such care. In this study, we show that non-invasive electrical measurements and the use of classifier software can be combined with cellular phone technology to produce inexpensive tissue characterization. This concept was demonstrated by the use of a Support Vector Machine (SVM) classifier to distinguish through the cellular phone between heart and kidney tissue via the non-invasive multi-frequency electrical measurements acquired around the tissues. After the measurements were performed at a remote site, the raw data were transmitted through the cellular phone to a central computational site and the classifier was applied to the raw data. The results of the tissue analysis were returned to the remote data measurement site. The classifiers correctly determined the tissue type with a specificity of over 90%. When used for the detection of malignant tumors, classifiers can be designed to produce false positives in order to ensure that no tumors will be missed. This mode of operation has applications in remote non-invasive tissue diagnostics in situ in the body, in combination with medical imaging, as well as in remote diagnostics of biopsy samples in vitro. PMID:19365554

  19. Non-invasive diagnosis of advanced fibrosis and cirrhosis.

    PubMed

    Sharma, Suraj; Khalili, Korosh; Nguyen, Geoffrey Christopher

    2014-12-01

    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. PMID:25492996

  20. 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

  1. 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

  2. Towards non-invasive characterization of breast cancer and cancer metabolism with diffuse optics

    PubMed Central

    Busch, David R.; Choe, Regine; Durduran, Turgut; Yodh, Arjun G.

    2013-01-01

    We review recent developments in diffuse optical imaging and monitoring of breast cancer, i.e. optical mammography. Optical mammography permits non-invasive, safe and frequent measurement of tissue hemodynamics oxygen metabolism and components (lipids, water, etc.), the development of new compound indices indicative of the risk and malignancy, and holds potential for frequent non-invasive longitudinal monitoring of therapy progression. PMID:24244206

  3. 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. PMID:27091626

  4. Multiparametric [18F]Fluorodeoxyglucose/ [18F]Fluoromisonidazole Positron Emission Tomography/ Magnetic Resonance Imaging of Locally Advanced Cervical Cancer for the Non-Invasive Detection of Tumor Heterogeneity: A Pilot Study

    PubMed Central

    Andrzejewski, Piotr; Baltzer, Pascal; Polanec, Stephan H.; Sturdza, Alina; Georg, Dietmar; Helbich, Thomas H.; Karanikas, Georgios; Grimm, Christoph; Polterauer, Stephan; Poetter, Richard; Wadsak, Wolfgang; Mitterhauser, Markus; Georg, Petra

    2016-01-01

    Objectives To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT). Materials and Methods Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis. Results All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05–0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity. Conclusion MP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT. PMID:27167829

  5. 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.

  6. [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. PMID:25962254

  7. 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

  8. 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. PMID:27162784

  9. 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.

  10. Physiology of non-invasive respiratory support.

    PubMed

    Alexiou, Stamatia; Panitch, Howard B

    2016-06-01

    Non-invasive ventilation (NIV) is used in neonates to treat extrathoracic and intrathoracic airway obstruction, parenchymal lung disease and disorders of control of breathing. Avoidance of airway intubation is associated with a reduction in the incidence of chronic lung disease among preterm infants with respiratory distress syndrome. Use of nasal continuous positive airway pressure (nCPAP) may help establish and maintain functional residual capacity (FRC), decrease respiratory work, and improve gas exchange. Other modes of non-invasive ventilation, which include heated humidified high-flow nasal cannula therapy (HHHFNC), nasal intermittent mandatory ventilation (NIMV), non-invasive pressure support ventilation (NI-PSV), and bi-level CPAP (SiPAP™), have also been shown to provide additional benefit in improving breathing patterns, reducing work of breathing, and increasing gas exchange when compared with nCPAP. Newer modes, such as neurally adjusted ventilatory assist (NAVA), hold the promise of improving patient-ventilator synchrony and so might ultimately improve outcomes for preterm infants with respiratory distress. PMID:26923501

  11. 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.

  12. Innovative non-invasive analysis techniques for cultural heritage using terahertz technology

    NASA Astrophysics Data System (ADS)

    Fukunaga, Kaori; Hosako, I.

    2010-08-01

    Terahertz (THz) spectroscopy and THz imaging techniques are expected to have great potential for carrying out the non-invasive analysis of artworks. THz waves can penetrate opaque materials and they can perform three-dimensional material mapping non-destructively by spectroscopic imaging. Several attempts have been made to analyse artworks. Clear results, such as imaging of hidden art by using model paintings, have been obtained by many institutions. We succeeded to observe the first ever non-invasive cross-sectional image of a tempera masterpiece by Giotto. These results prove that THz technology can yield useful information in art conservation science.

  13. 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

  14. 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

    2014-07-01

    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. PMID:24920208

  15. 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

  16. 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.

  17. Multiphoton and photothermal imaging of molecular events in cancer

    NASA Astrophysics Data System (ADS)

    Skala, Melissa

    2010-10-01

    Optical techniques are attractive for monitoring disease processes in living tissues because they are relatively cheap, non-invasive and provide a wealth of functional information. Multiphoton microscopy (MPM) and Optical Coherence Tomography (OCT) are two types of three-dimensional optical imaging modalities that have demonstrated great utility in pre-clinical models of disease. These techniques are particularly useful for identifying metabolic and molecular biomarkers in cancer. These biomarkers can be used to identify the mechanisms of tumor growth, and to predict the response of a particular tumor to treatment. Specifically, MPM of the co-enzymes NADH and FAD was used to quantify metabolic changes associated with developing cancers in vivo. This imaging technique exploits intrinsic sources of tissue contrast and thus does not require contrast agents. Ongoing work combines this metabolic imaging technique with vascular imaging to provide a comprehensive picture of oxygen supply and demand with tumor therapy. Molecular signaling represents a third critical component in tumor physiology. To this end we have recently developed photothermal OCT, which combines coherent detection with laser-heated gold nanoparticles to achieve high-resolution molecular contrast at deeper depths than MPM. This multi-functional imaging platform will provide unprecedented insight into oxygen supply and demand, and molecular signaling in response to tumor growth and targeted cancer therapies in pre-clinical models.

  18. 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.

  19. [Non invasive ventilation in the emergency setting].

    PubMed

    Wilhelm, Laetitia; Della Santa, Vincent; Hanhart, Walter-Alexandre

    2015-08-12

    Before the development of non invasive ventilation (NIV), endotracheal intubation was the only ventilatory therapy available in case of severe respiratory distress and acute respiratory failure. NIV used to be employed in intensive care settings only. Nowadays, the use of NIV has been democratized to include the emergency room, and the pre-hospital care setting for treatment of acute respiratory failure. Cardiogenic pulmonary edema and acute exacerbation of COPD are indications of choice, since NIV improves mortality. The efficiency of the therapy depends on early treatment; however, endotracheal intubation should not be delayed when it becomes necessary. PMID:26449102

  20. 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

  1. Molecular Imaging in Genetic Medicine

    PubMed Central

    Jacob, Ayden; Van Gestel, Frederick; Yaghoubi, Shahriar

    2016-01-01

    The field of biomedical imaging has made significant advances in recent times. This includes extremely high-resolution anatomic imaging and functional imaging of physiologic and pathologic processes as well as novel modalities in optical imaging to evaluate molecular features within the cellular environment. The latter has made it possible to image phenotypic markers of various genotypes that are implicated in human development, behavior, and disease. This article discusses the role of molecular imaging in genetic and precision medicine.  PMID:27186447

  2. 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

  3. 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.

  4. Diagnosis and therapies for gastric non-invasive neoplasia

    PubMed Central

    Kato, Motohiko

    2015-01-01

    There has been a great discrepancy of pathological diagnosis for gastric non-invasive neoplasia/dysplasia between Japanese and western pathologists. In Japan, lesions that most western pathologists diagnose as dysplasia are often considered adenocarcinoma based on nuclear and structural atypia regardless of the presence of invasion. In the Vienna classification, gastric non-invasive intraepithelial neoplasia (NIN) were divided into low grade and high grade (including intra-mucosal cancer of Japanese criteria). The diagnosis by both endoscopy and pathology of biopsy specimen is difficult. Recent advances of diagnostic modality such as magnified endoscopy and imaged enhanced endoscopy is expected to improve the diagnostic yield for NIN. There are two treatment strategies for NIN, observation and diagnostic therapy by endoscopic resection (ER). ER is acceptable because of its less invasiveness and high local control rate, on the other hand, cancer-developing rate of low-grade NIN is reported to be low. Therefore there is controversy for the treatment of gastric NIN. Prospective study based on unified pathological definition is required in the future. PMID:26640329

  5. Use of Doppler ultrasound for non-invasive urodynamic diagnosis

    PubMed Central

    Ozawa, Hideo; Watanabe, Toyohiko; Uematsu, Katsutoshi; Sasaki, Katsumi; Inoue, Miyabi; Kumon, Hiromi

    2009-01-01

    Objectives: A totally non-invasive transperineal urodynamic technique using Doppler ultrasonography has been developed. Methods: Since normal urine does not have blood cells, urine was thought not to produce the Doppler effects. However, basic studies confirmed that the decrease of pressure at high velocity (Bernouilli effect) caused dissolved gas to form microbubbles, which are detected by Doppler ultrasonography. Subjects sat and the probe was advanced via remote control to achieve gentle contact with the perineal skin. The digital uroflow data signals and the color Doppler ultrasound video images were processed on a personal computer. The flow-velocity curves from two sites; the distal prostatic urethra just above the external sphincter (V1) and the sphincteric urethra (V2) were plotted against time. The parameters of both the pressure-flow studies and the Doppler ultrasound urodynamic studies were compared in men who had various degrees of obstruction. Results: Functional cross-sectional area at prostatic urethra (A1), calculated by Qmax/V1, was lower in the group of bladder outlet obstruction (BOO) vs. control group. Velocity ratio (VR), which was calculated by V1/V2, was the parameter having the best correlation with BOO index, though A1 had a similar correlation. This method is viable to diagnose the degree of BOO. Conclusions: The development of non-invasive Doppler ultrasound videourodynamics (Doppler UDS) will dramatically expand the information on voiding function. PMID:19468440

  6. ADVANCES IN MOLECULAR IMAGING OF PANCREATIC BETA CELLS

    PubMed Central

    Lin, Mai; Lubag, Angelo; McGuire, Michael J.; Seliounine, Serguei Y.; Tsyganov, Edward N.; Antich, Peter P.; Sherry, A. Dean; Brown, Kathlynn C.; Sun, Xiankai

    2009-01-01

    The development of non-invasive imaging methods for early diagnosis of the beta cell associated metabolic diseases, including type 1 and type 2 diabetes (T1D and T2D), has recently drawn considerable interest from the molecular imaging community as well as clinical investigators. Due to the challenges imposed by the location of the pancreas, the sparsely dispersed beta cell population within the pancreas, and the poor understanding of the pathogenesis of the diseases, clinical diagnosis of beta cell abnormalities is still limited. Current diagnostic methods are invasive, often inaccurate, and usually performed post-onset of the disease. Advances in imaging techniques for probing beta cell mass and function are needed to address this critical health care problem. A variety of currently available imaging techniques have been tested for the assessment of the pancreatic beta cell islets. Here we discuss the current advances in magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and nuclear imaging for the study of beta cell diseases. Spurred by early successes in nuclear imaging techniques for beta cells, especially positron emission tomography (PET), the need for beta cell specific ligands has expanded. Progress in the field for obtaining such ligands is presented. Additionally, we report our preliminary efforts of developing such a peptidic ligand for PET imaging of the pancreatic beta cells. PMID:18508529

  7. 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.

  8. Molecular probes for cardiovascular imaging.

    PubMed

    Liang, Grace; Nguyen, Patricia K

    2016-08-01

    Molecular probes provide imaging signal and contrast for the visualization, characterization, and measurement of biological processes at the molecular level. These probes can be designed to target the cell or tissue of interest and must be retained at the imaging site until they can be detected by the appropriate imaging modality. In this article, we will discuss the basic design of molecular probes, differences among the various types of probes, and general strategies for their evaluation of cardiovascular disease. PMID:27189171

  9. Molecular Imaging Using Nanoparticle Quenchers of Cerenkov Luminescence

    PubMed Central

    Thorek, Daniel L.J.; Das, Sudeep; Grimm, Jan

    2014-01-01

    Cerenkov luminescence (CL) imaging is an emerging technique that collects the visible photons produced by radioisotopes. Here, we have investigated molecular imaging strategies by modulating CL signal off. Utilizing a combination of clinically approved agents, and their analogues, we demonstrate the noninvasive molecularly specific detection of cancer. CL was modulated in vitro in a dose dependent manner using approved small molecules (Lymphazurin), as well as the clinically approved Feraheme and other preclinical superparamagnetic iron oxide nanoparticles (SPIO). To evaluate the quenching of CL in vivo, two strategies were pursued. [18F]-FDG was imaged by PET and CL in tumors prior to and following accumulation of nanoparticles. Initially, non-targeted particles were administered to mice bearing tumors in order to attenuate CL. For targeted imaging, a dual tumor model (expressing the human somatostatin receptor subtype-2 (hSSTr2) and a control negative cell line) was used. Targeting hSSTr2 with octreotate-conjugated SPIO, we demonstrate quenched CL enabling non-invasive distinction between tumors’ molecular expression profiles. In this work, we demonstrate quenching of Cerenkov emissions in several proof of principle models using a combination of approved agents and nanoparticle platforms to provide disease relevant information including tumor vascularity and specific antigen expression. PMID:24861843

  10. Molecular imaging using nanoparticle quenchers of Cerenkov luminescence.

    PubMed

    Thorek, Daniel L J; Das, Sudeep; Grimm, Jan

    2014-09-24

    Cerenkov luminescence (CL) imaging is an emerging technique that collects the visible photons produced by radioisotopes. Here, molecular imaging strategies are investigated that switch the CL signal off. The noninvasive molecularly specific detection of cancer is demonstrated utilizing a combination of clinically approved agents, and their analogues. CL is modulated in vitro in a dose dependent manner using approved small molecules (Lymphazurin), as well as the clinically approved Feraheme and other preclinical superparamagnetic iron oxide nanoparticles (SPIO). To evaluate the quenching of CL in vivo, two strategies are pursued. [(18) F]-FDG is imaged by PET and CL in tumors prior to and following accumulation of nanoparticles. Initially, non-targeted particles are administered to mice bearing tumors in order to attenuate CL. For targeted imaging, a dual tumor model (expressing the human somatostatin receptor subtype-2 (hSSTr2) and a control negative cell line) is used. Targeting hSSTr2 with octreotate-conjugated SPIO, quenched CL enabling non-invasive distinction between tumors' molecular expression profiles is demonstrated. In this work, the quenching of Cerenkov emissions is demonstrated in several proof of principle models using a combination of approved agents and nanoparticle platforms to provide disease relevant information including tumor vascularity and specific antigen expression. PMID:24861843

  11. Non-invasive diagnosis of alcoholic liver disease.

    PubMed

    Mueller, Sebastian; Seitz, Helmut Karl; Rausch, Vanessa

    2014-10-28

    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

  12. 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

  13. 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

  14. Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging.

    PubMed

    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

  15. 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

  16. Non-invasive measurments of intense relativistic electron beam size

    NASA Astrophysics Data System (ADS)

    Ekdahl, Carl; McCuistian, Trent; Moir, David; Rodriguez, Patrick; Broste, William; Johnson, Jeff

    2000-10-01

    To understand relativistic electron beam transport dynamics the size of the beam is often measured using invasive techniques such as imaging the Cerenkov or OTR light emitted from a screen inserted into the beam. These techniques would completely disrupt the DARHT 2 beam, so we are developing a non-invasive method using diamagnetic loops. We show that through conservation of canonical angular momentum the RMS radius of the beam can be found by measuring the magnetic flux excluded by the diamagnetic beam. Furthermore, this measurement is shown to be independent of the details of the beam radial current profile for DARHT 2 parameters. We present results from our test and calibration experiments, as well as results of beam radius measurements on the 20-MeV DARHT 1 accelerator.

  17. A Molecular Imaging Paradigm to Rapidly Profile Response to Angiogenesis-directed Therapy in Small Animals

    PubMed Central

    Virostko, John; Xie, Jingping; Hallahan, Dennis E.; Arteaga, Carlos L.; Gore, John C.; Manning, H. Charles

    2009-01-01

    Purpose The development of novel angiogenesis-directed therapeutics is hampered by the lack of non-invasive imaging metrics capable of assessing treatment response. We report the development and validation of a novel molecular imaging paradigm to rapidly assess response to angiogenesis-directed therapeutics in preclinical animal models. Procedures A monoclonal antibody-based optical imaging probe targeting vascular endothelial growth factor receptor-2 (VEGFR2) expression was synthesized and evaluated in vitro and in vivo via multispectral fluorescence imaging. Results The optical imaging agent demonstrated specificity for the target receptor in cultured endothelial cells and in vivo. The agent exhibited significant accumulation within 4T1 xenograft tumors. Mice bearing 4T1 xenografts and treated with sunitinib exhibited both tumor growth arrest and decreased accumulation of NIR800-αVEGFR2ab compared to untreated cohorts (p=0.0021). Conclusions Molecular imaging of VEGFR2 expression is a promising non-invasive biomarker for assessing angiogenesis and evaluating the efficacy of angiogenesis-directed therapies. PMID:19130143

  18. Time-resolved molecular imaging

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  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. Molecular application of spectral photoacoustic imaging in pancreatic cancer pathology

    NASA Astrophysics Data System (ADS)

    Lakshman, Minalini; Hupple, Clinton; Lohse, Ines; Hedley, David; Needles, Andrew; Theodoropoulos, Catherine

    2012-12-01

    Spectral imaging is an advanced photo-acoustic (PA) mode that can discern optical absorption of contrast agent(s) in the tissue micro-environment. This advancement is made possible by precise control of optical wavelength using a tunable pulsed laser, ranging from 680-970 nm. Differential optical absorption of blood oxygenation states makes spectral imaging of hemoglobin ideal to investigate remodeling of the tumor microenvironment- a molecular change that renders resistance to standard cancer treatment. Approach: Photo-acoustic imaging was performed on the Vevo® LAZR system (VisualSonics) at 5-20 Hz. Deep abdominal imaging was accomplished with a LZ250D probe at a center frequency of 21MHz and an axial resolution of 75 μm. The tumor model was generated in an immune compromised mouse by surgical implantation of primary patient derived tumors, in the pancreas. Results: Spectral imaging for oxygen saturation at 750 nm and 850 nm characterized this tumor with a poorly oxygenated core surrounded by a well oxygenated periphery. Multispectral imaging identified a sub region in the core with a four-fold signal exclusively at 750 and 800 nm. A co-registered 2D image of this region was shown to be echogenic and calcification was suspected. Perfusion imaging with contrast enhanced ultrasound using microbubbles (Vevo MicroMarker® contrast agents, VisualSonics) identified functional vessels towards this sub region. Histology confirmed calcification and vascularization in the tumor core. Taken together, non-invasive characterization of the tumor microenvironment using photo-acoustics rendered spectral imaging a sensitive tool to monitor molecular changes representative of progression of pancreatic cancer that kills within 6 months of diagnosis.

  1. Non invasive sensing technologies for cultural heritage management and fruition

    NASA Astrophysics Data System (ADS)

    Soldovieri, Francesco; Masini, Nicola

    2016-04-01

    The relevance of the information produced by science and technology for the knowledge of the cultural heritage depends on the quality of the feedback and, consequently, on the "cultural" distance between scientists and end-users. In particular, the solution to this problem mainly resides in the capability of end-users' capability to assess and transform the knowledge produced by diagnostics with regard to: information on both cultural objects and sites (decay patterns, vulnerability, presence of buried archaeological remains); decision making (management plan, conservation project, and excavation plan). From our experience in the field of the cultural heritage and namely the conservation, of monuments, there is a significant gap of information between technologists (geophysicists/physicists/engineers) and end-users (conservators/historians/architects). This cultural gap is due to the difficulty to interpret "indirect data" produced by non invasive diagnostics (i.e. radargrams/thermal images/seismic tomography etc..) in order to provide information useful to improve the historical knowledge (e.g. the chronology of the different phases of a building), to characterise the state of conservation (e.g. detection of cracks in the masonry) and to monitor in time cultural heritage artifacts and sites. The possible answer to this difficulty is in the set-up of a knowledge chain regarding the following steps: - Integrated application of novel and robust data processing methods; - Augmented reality as a tool for making easier the interpretation of non invasive - investigations for the analysis of decay pathologies of masonry and architectural surfaces; - The comparison between direct data (carrots, visual inspection) and results from non-invasive tests, including geophysics, aims to improve the interpretation and the rendering of the monuments and even of the archaeological landscapes; - The use of specimens or test beds for the detection of archaeological features and

  2. Non invasive monitoring in mechanically ventilated pediatric patients.

    PubMed

    Al-Subu, Awni M; Rehder, Kyle J; Cheifetz, Ira M; Turner, David A

    2014-12-01

    Cardiopulmonary monitoring is a key component in the evaluation and management of critically ill patients. Clinicians typically rely on a combination of invasive and non-invasive monitoring to assess cardiac output and adequacy of ventilation. Recent technological advances have led to the introduction: of continuous non-invasive monitors that allow for data to be obtained at the bedside of critically ill patients. These advances help to identify hemodynamic changes and allow for interventions before complications occur. In this manuscript, we highlight several important methods of non-invasive cardiopulmonary monitoring, including capnography, transcutaneous monitoring, pulse oximetry, and near infrared spectroscopy. PMID:25119483

  3. Improving non-invasive ventilation documentation.

    PubMed

    Smith, Matthew; Elkheir, Natalie

    2014-01-01

    Record keeping for patients on non-invasive ventilation (NIV) at St. Georges Hospital is poor. The initial NIV prescription is often not recorded, and changes to the NIV prescription or the rationale for the changes (ABG results) are also poorly documented. This leads to confusion for nurses/doctors as to what the correct settings are, meaning patients could receive ineffective ventilation. The use of NIV is also poorly recorded by nursing staff meaning that doctors are unsure if the prescribed NIV is being achieved. This can lead to treatment being escalated unnecessarily in the event of treatment failure. Non-invasive ventilation (NIV) is the provision of ventilatory support in the form of positive pressure via the patient's upper airway using a mask or similar device. NIV is indicated for treatment of acute hypercapnic respiratory failure, of which there are many causes, though COPD is the indication in up to 70% of cases.[1] British Thoracic Society (BTS) guidelines for NIV suggest that the rationale for commencing a patient on NIV and the proposed settings should be clearly documented.[2] Clinicians cannot effectively tailor changes to the patients NIV settings if this information is not clearly recorded, which could lead to increased time requiring NIV or NIV failure. Three main areas were considered important to measure for this project. The initial prescription of the NIV, changes to the NIV settings, and nursing documentation surrounding NIV. A baseline measurement of NIV documentation for two weeks found NIV documentation to globally very poor. NIV was formally prescribed 29% of the time, full detail of intended settings were documented 57% of the time, the decision to commence NIV was discussed with the respiratory consultant/SpR just 29% of the time and on no occasion was a decision regarding escalation of treatment recorded. Eighteen changes were made to the NIV settings. These were formally prescribed 22% of the time and detail of the intended

  4. Molecular SPECT Imaging: An Overview

    PubMed Central

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

    2011-01-01

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

  5. Targeted molecular imaging in oncology.

    PubMed

    Yang, David J; Kim, E Edmund; Inoue, Tomio

    2006-01-01

    Improvement of scintigraphic tumor imaging is extensively determined by the development of more tumor specific radiopharmaceuticals. Thus, to improve the differential diagnosis, prognosis, planning and monitoring of cancer treatment, several functional pharmaceuticals have been developed. Application of molecular targets for cancer imaging, therapy and prevention using generator-produced isotopes is the major focus of ongoing research projects. Radionuclide imaging modalities (positron emission tomography, PET; single photon emission computed tomography, SPECT) are diagnostic cross-sectional imaging techniques that map the location and concentration of radionuclide-labeled radiotracers. 99mTc- and 68Ga-labeled agents using ethylenedicysteine (EC) as a chelator were synthesized and their potential uses to assess tumor targets were evaluated. 99mTc (t1/2 = 6 hr, 140 keV) is used for SPECT and 68Ga (t1/2 = 68 min, 511 keV) for PET. Molecular targets labeled with Tc-99m and Ga-68 can be utilized for prediction of therapeutic response, monitoring tumor response to treatment and differential diagnosis. Molecular targets for oncological research in (1) cell apoptosis, (2) gene and nucleic acid-based approach, (3) angiogenesis (4) tumor hypoxia, and (5) metabolic imaging are discussed. Numerous imaging ligands in these categories have been developed and evaluated in animals and humans. Molecular targets were imaged and their potential to redirect optimal cancer diagnosis and therapeutics were demonstrated. PMID:16485568

  6. Design and Development of Molecular Imaging Probes

    PubMed Central

    Chen, Kai; Chen, Xiaoyuan

    2013-01-01

    Molecular imaging, the visualization, characterization and measurement of biological processes at the cellular, subcellular level, or even molecular level in living subjects, has rapidly gained importance in the dawning era of personalized medicine. Molecular imaging takes advantage of the traditional diagnostic imaging techniques and introduces molecular imaging probes to determine the expression of indicative molecular markers at different stages of diseases and disorders. As a key component of molecular imaging, molecular imaging probe must be able to specifically reach the target of interest in vivo while retaining long enough to be detected. A desirable molecular imaging probe with clinical translation potential is expected to have unique characteristics. Therefore, design and development of molecular imaging probe is frequently a challenging endeavor for medicinal chemists. This review summarizes the general principles of molecular imaging probe design and some fundamental strategies of molecular imaging probe development with a number of illustrative examples. PMID:20388106

  7. Aortic stenosis in adults. Non-invasive estimation of pressure differences by continuous wave Doppler echocardiography.

    PubMed Central

    Hegrenaes, L; Hatle, L

    1985-01-01

    The peak and mean aortic transvalvar pressure differences measured invasively and non-invasively by continuous wave Doppler echocardiography were compared in 87 consecutive patients with aortic stenosis. The mean values were calculated from the maximal velocities of the aortic jet recorded with a spectral display of the Doppler frequency shifts and by applying a modified Bernoulli equation. Technically satisfactory velocity curves for estimating the mean pressure differences could not be obtained in three patients and invasive measurements were not obtained in two. In all patients the peak transvalvar pressure difference was calculated since the aortic jet was identified non-invasively. The peak and mean pressure differences measured invasively and non-invasively correlated well--with only minor underestimation of the pressure differences measured with the Doppler technique--regardless of age, sex, and the presence or absence of aortic valvar regurgitation, or other valvar lesions. With a systematic search for the highest velocities in the aortic jet and with on line spectral analysis of the Doppler frequencies the peak and the mean aortic pressure differences can be determined non-invasively with a high degree of precision in almost all patients. Images PMID:4052281

  8. Modern non-invasive mechanical ventilation turns 25.

    PubMed

    Díaz Lobato, Salvador; Mayoralas Alises, Sagrario

    2013-11-01

    The history of non-invasive mechanical ventilation goes back more than 100 years, but it was not until 1987 when what we could call "modern" non-invasive mechanical ventilation was developed. The description of Delaubier and Rideau of a patient with Duchenne's disease who had been effectively ventilated through a nasal mask marked the start of a new era in the history of non-invasive mechanical ventilation. Over these last 25years, we have witnessed exponential growth in its use, field of activity and technological advances on an exciting fast-paced track. We believe that it is time to review the main milestones that have marked the development of non-invasive mechanical ventilation to date, while paying homage to this therapeutic method that has contributed so much to the advancement of respiratory medicine in the last 25years. PMID:23347549

  9. [Molecular imaging in neurological diseases].

    PubMed

    Reimold, M; la Fougère, C

    2016-07-01

    In neurodegeneration and in neuro-oncology, the standard imaging procedure, magnetic resonance imaging (MRI), shows limited sensitivity and specificity. Molecular imaging with specific positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers allows various molecular targets and metabolic processes to be assessed and is thus a valuable adjunct to MRI. Two important examples are referred to here: amino acid transport for neuro-oncological issues, and the recently approved PET tracers for detecting amyloid depositions during the preclinical stage of Alzheimer's disease. This review discusses the clinical relevance and indications for the following nuclear medicine imaging procedures: amyloid PET, (18)F-fluorodeoxyglucose (FDG)-PET, and dopamine transporter (DaT)-SPECT for the diagnosis of dementia and the differential diagnosis of Parkinson's disease, in addition to amino acid PET for the diagnosis of brain tumors and somatostatin receptor imaging in meningioma. PMID:27306201

  10. A computer controlled non-invasive haemodynamic monitoring system.

    PubMed

    McMenemin, I M; Kenny, G N

    1988-10-01

    A system for the non-invasive monitoring, recording and storing haemodynamic indices has been developed using an Apple II microcomputer, a Dinamap automatic arterial pressure monitor and a non-invasive cardiac output monitor based on bio-electrical impedance. This system was used during the induction and maintenance of anaesthesia. Numerical and graphical displays of heart rate, arterial pressure, cardiac output and systemic vascular resistance are available. A print-out of data can be produced for later analysis. PMID:3190976

  11. Non-invasive photo acoustic approach for human bone diagnosis.

    PubMed

    Thella, Ashok Kumar; Rizkalla, James; Helmy, Ahdy; Suryadevara, Vinay Kumar; Salama, Paul; Rizkalla, Maher

    2016-12-01

    The existing modalities of bone diagnosis including X-ray and ultrasound may cite drawback in some cases related to health issues and penetration depth, while the ultrasound modality may lack image quality. Photo acoustic approach however, provides light energy to the acoustic wave, enabling it to activate and respond according to the propagating media (which is type of bones in this case). At the same time, a differential temperature change may result in the bio heat response, resulting from the heat absorbed across the multiple materials under study. In this work, we have demonstrated the features of using photo acoustic modality in order to non-invasively diagnose the type of human bones based on their electrical, thermal, and acoustic properties that differentiate the output response of each type. COMSOL software was utilized to combine both acoustic equations and bio heat equations, in order to study both the thermal and acoustic responses through which the differential diagnosis can be obtained. In this study, we solved both the acoustic equation and bio heat equations for four types of bones, bone (cancellous), bone (cortical), bone marrow (red), and bone marrow (yellow). 1 MHz acoustic source frequency was chosen and 10(5) W/m(2) power source was used in the simulation. The simulation tested the dynamic response of the wave over a distance of 5 cm from each side for the source. Near 2.4 cm was detected from simulation from each side of the source with a temperature change of within 0.5 K for various types of bones, citing a promising technique for a practical model to detect the type of bones via the differential temperature as well as the acoustic was response via the multiple materials associated with the human bones (skin and blood). The simulation results suggest that the PA technique may be applied to non-invasive diagnosis for the different types of bones, including cancerous bones. A practical model for detecting both the temperature change via

  12. An optical approach for non-invasive blood clot testing

    NASA Astrophysics Data System (ADS)

    Kalchenko, Vyacheslav; Brill, Alexander; Fine, Ilya; Harmelin, Alon

    2007-02-01

    Physiological blood coagulation is an essential biological process. Current tests for plasma coagulation (clotting) need to be performed ex vivo and require fresh blood sampling for every test. A recently published work describes a new, noninvasive, in vivo approach to assess blood coagulation status during mechanical occlusion1. For this purpose, we have tested this approach and applied a controlled laser beam to blood micro-vessels of the mouse ear during mechanical occlusion. Standard setup for intravital transillumination videomicroscopy and laser based imaging techniques were used for monitoring the blood clotting process. Temporal mechanical occlusion of blood vessels in the observed area was applied to ensure blood flow cessation. Subsequently, laser irradiation was used to induce vascular micro-injury. Changes in the vessel wall, as well as in the pattern of blood flow, predispose the area to vascular thrombosis, according to the paradigm of Virchow's triad. In our experiments, two elements of Virchow's triad were used to induce the process of clotting in vivo, and to assess it optically. We identified several parameters that can serve as markers of the blood clotting process in vivo. These include changes in light absorption in the area of illumination, as well as changes in the pattern of the red blood cells' micro-movement in the vessels where blood flow is completely arrested. Thus, our results indicate that blood coagulation status can be characterized by non-invasive, in vivo methodologies.

  13. Non invasive tools for the diagnosis of liver cirrhosis

    PubMed Central

    Soresi, Maurizio; Giannitrapani, Lydia; Cervello, Melchiorre; Licata, Anna; Montalto, Giuseppe

    2014-01-01

    Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis. PMID:25561782

  14. Application of optical non-invasive methods in skin physiology

    NASA Astrophysics Data System (ADS)

    Lademann, J.; Patzelt, A.; Darvin, M.; Richter, H.; Antoniou, C.; Sterry, W.; Koch, S.

    2008-05-01

    In the present paper the application of optical non-invasive methods in dermatology and cosmetology is discussed. Laser scanning microscopy (LSM) and optical coherent tomography (OCT) are the most promising methods for this application. Using these methods, the analysis of different skin parameters like dryness and oiliness of the skin, the barrier function and the structure of furrows and wrinkles are discussed. Additionally the homogeneity of distribution of topically applied creams, as well as their penetration into the skin were investigated. It is shown that these methods are highly valuable in dermatology for diagnostic and therapy control and for basic research, for instance in the field of structure analysis of hair follicles and sweat glands. The vertical images of the tissue produced by OCT can be easily compared with histological sections. Unfortunately, the resolution of the OCT technique is not high enough to carry out measurements on a cellular level, as is possible by LSM. LSM has the advantage that it can be used for the investigation of penetration and storage processes of topically applied substances, if these substances have fluorescent properties or if they are fluorescent-labelled.

  15. Facilitate Insight by Non-Invasive Brain Stimulation

    PubMed Central

    Chi, Richard P.; Snyder, Allan W.

    2011-01-01

    Our experiences can blind us. Once we have learned to solve problems by one method, we often have difficulties in generating solutions involving a different kind of insight. Yet there is evidence that people with brain lesions are sometimes more resistant to this so-called mental set effect. This inspired us to investigate whether the mental set effect can be reduced by non-invasive brain stimulation. 60 healthy right-handed participants were asked to take an insight problem solving task while receiving transcranial direct current stimulation (tDCS) to the anterior temporal lobes (ATL). Only 20% of participants solved an insight problem with sham stimulation (control), whereas 3 times as many participants did so (p = 0.011) with cathodal stimulation (decreased excitability) of the left ATL together with anodal stimulation (increased excitability) of the right ATL. We found hemispheric differences in that a stimulation montage involving the opposite polarities did not facilitate performance. Our findings are consistent with the theory that inhibition to the left ATL can lead to a cognitive style that is less influenced by mental templates and that the right ATL may be associated with insight or novel meaning. Further studies including neurophysiological imaging are needed to elucidate the specific mechanisms leading to the enhancement. PMID:21311746

  16. Small unilamellar vesicles: a platform technology for molecular imaging of brain tumors

    NASA Astrophysics Data System (ADS)

    Iqbal, Umar; Albaghdadi, Homam; Nieh, Mu-Ping; Tuor, Ursula I.; Mester, Zoltan; Stanimirovic, Danica; Katsaras, John; Abulrob, Abedelnasser

    2011-05-01

    Molecular imaging enables the non-invasive investigation of cellular and molecular processes. Although there are challenges to overcome, the development of targeted contrast agents to increase the sensitivity of molecular imaging techniques is essential for their clinical translation. In this study, spontaneously forming, small unilamellar vesicles (sULVs) (30 nm diameter) were used as a platform to build a bimodal (i.e., optical and magnetic resonance imaging (MRI)) targeted contrast agent for the molecular imaging of brain tumors. sULVs were loaded with a gadolinium (Gd) chelated lipid (Gd-DPTA-BOA), functionalized with targeting antibodies (anti-EGFR monoclonal and anti-IGFBP7 single domain), and incorporated a near infrared dye (Cy5.5). The resultant sULVs were characterized in vitro using small angle neutron scattering (SANS), phantom MRI and dynamic light scattering (DLS). Antibody targeted and nontargeted Gd loaded sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice using time domain optical imaging and MRI. The results demonstrated that a spontaneously forming, nanosized ULVs loaded with a high payload of Gd can selectively target and image, using MR and optical imaging, brain tumor vessels when functionalized with anti-IGFBP7 single domain antibodies. The unique features of these targeted sULVs make them promising molecular MRI contrast agents.

  17. Small Unilamellar Vesicles: A Platform Technology for Molecular Imaging of Brain Tumors

    SciTech Connect

    Iqbal, U; Albaghdadi, H; Nieh, Mu-Ping; Tuor, U.I; Mester, Z; Stanimirovic, D; Katsaras, John; Abulrob, A

    2011-01-01

    Molecular imaging enables the non-invasive investigation of cellular and molecular processes. Although there are challenges to overcome, the development of targeted contrast agents to increase the sensitivity of molecular imaging techniques is essential for their clinical translation. In this study, spontaneously forming, small unilamellar vesicles (sULVs) (30 nm diameter) were used as a platform to build a bimodal (i.e., optical and magnetic resonance imaging (MRI)) targeted contrast agent for the molecular imaging of brain tumors. sULVs were loaded with a gadolinium (Gd) chelated lipid (Gd-DPTA-BOA), functionalized with targeting antibodies (anti-EGFR monoclonal and anti-IGFBP7 single domain), and incorporated a near infrared dye (Cy5.5). The resultant sULVs were characterized in vitro using small angle neutron scattering (SANS), phantom MRI and dynamic light scattering (DLS). Antibody targeted and nontargeted Gd loaded sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice using time domain optical imaging and MRI. The results demonstrated that a spontaneously forming, nanosized ULVs loaded with a high payload of Gd can selectively target and image, using MR and optical imaging, brain tumor vessels when functionalized with anti-IGFBP7 single domain antibodies. The unique features of these targeted sULVs make them promising molecular MRI contrast agents.

  18. Optical molecular imaging in PDT

    NASA Astrophysics Data System (ADS)

    Mitra, Soumya; Snyder, John W.; Foster, Thomas H.

    2007-02-01

    Motivated by recent successes in fluorescence imaging of whole mount tissue preparations and by rapid progress in the fields of molecular imaging and molecular biology, we are exploring a number of applications of optical fluorescence imaging in superficial murine tumor models in vivo. Imaging the PDT-induced expression of the heat shock protein 70 (HSP70) in cells and in vivo is accomplished using stably transfected EMT6 cells in which the gene for GFP is under the control of the HSP70 promoter. These cells readily form solid tumors in BALB/c mice, enabling the direct imaging of the extent and time course of the activation of this promoter, with each mouse serving as its own control. Imaging of similarly transfected EMT6 cells with a HIF-1α/GFP fusion protein vector enables visualization of HIF-1α translocation to the nucleus. Recently, we have accomplished fluorescent labeling of surface antigens in vivo using intratumor and intravenous injection of fluorophore-conjugated antibodies. Injection of deep-red fluorophore-conjugated-anti-CD31 enables confocal fluorescence imaging of the tumor vasculature to depths of at least 100 microns. With the vessels rendered fluorescent in this way, a number of interesting studies become possible in the living mouse, including the direct visualization of photosensitizer distribution from perfused vessels. Using the appropriate fluorophore-conjugated antibodies, we have also been able to image infiltrating granulocytes in EMT6 tumors in response to PDT in vivo.

  19. Molecular Imaging of Plaque Vulnerability

    PubMed Central

    Tavakoli, Sina; Vashist, Aseem; Sadeghi, Mehran M.

    2014-01-01

    Over the past decade significant progress has been made in the development of novel imaging strategies focusing on the biology of the vessel wall for identification of vulnerable plaques. While the majority of these studies are still in the preclinical stage, few techniques (e.g., 18F-FDG and 18F-NaF PET imaging) have already been evaluated in clinical studies with promising results. Here, we will briefly review the pathobiology of atherosclerosis and discuss molecular imaging strategies that have been developed to target these events, with an emphasis on mechanisms that are associated with atherosclerotic plaque vulnerability. PMID:25124827

  20. Molecular nanomagnets as contrast agents for Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Rodríguez, Elisenda; Roig, Anna; Molins, Elies; Arús, Carles; Cabañas, Miquel; Quintero, María Rosa; Cerdán, Sebastián; Sanfeliu, Coral

    2003-03-01

    Magnetic resonance imaging (MRI) is a non-invasive technique used in medicine to produce high quality images of human body slices. In order to enhance the contrast between different organs or to reveal altered portions of them such necrosis or tumors, the administration of a contrast agent is highly convenient. Currently Gd-DTPA, a paramagnetic complex, is the most widely administered compound. In this context, we have assayed molecular nanomagnets as MRI contrast agents. The complex [(tacn)_6Fe_8(μ_3-O)_2(μ_2-OH)_12]Br_8·9H_2O^1(Fe8 in brief) has been evaluated and shorter relaxation times, T1 and T_2, have been obtained for Fe8 than those obtained for the commercial Gd-DTPA. No toxic effects have been observed at concentrations up to 1 mM of Fe8 in cultured cells. Phantom studies with T_1-weighted MRI at 9.4 Tesla suggest that Fe8 can have potentiality as T_1-contrast agent. ^1Wieghardt K Angew Chem Intl Ed Engl 23 1 (1984) 77

  1. The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis

    PubMed Central

    Chowdhury, R; Ganeshan, B; Irshad, S; Lawler, K; Eisenblätter, M; Milewicz, H; Rodriguez-Justo, M; Miles, K; Ellis, P; Groves, A; Punwani, S

    2014-01-01

    Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm. PMID:24597512

  2. Molecular imaging in cervical cancer.

    PubMed

    Khan, Sairah R; Rockall, Andrea G; Barwick, Tara D

    2016-06-01

    Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed. PMID:26859085

  3. Non-invasive pressure difference estimation from PC-MRI using the work-energy equation

    PubMed Central

    Donati, Fabrizio; Figueroa, C. Alberto; Smith, Nicolas P.; Lamata, Pablo; Nordsletten, David A.

    2015-01-01

    Pressure difference is an accepted clinical biomarker for cardiovascular disease conditions such as aortic coarctation. Currently, measurements of pressure differences in the clinic rely on invasive techniques (catheterization), prompting development of non-invasive estimates based on blood flow. In this work, we propose a non-invasive estimation procedure deriving pressure difference from the work-energy equation for a Newtonian fluid. Spatial and temporal convergence is demonstrated on in silico Phase Contrast Magnetic Resonance Image (PC-MRI) phantoms with steady and transient flow fields. The method is also tested on an image dataset generated in silico from a 3D patient-specific Computational Fluid Dynamics (CFD) simulation and finally evaluated on a cohort of 9 subjects. The performance is compared to existing approaches based on steady and unsteady Bernoulli formulations as well as the pressure Poisson equation. The new technique shows good accuracy, robustness to noise, and robustness to the image segmentation process, illustrating the potential of this approach for non-invasive pressure difference estimation. PMID:26409245

  4. Non-invasive pressure difference estimation from PC-MRI using the work-energy equation.

    PubMed

    Donati, Fabrizio; Figueroa, C Alberto; Smith, Nicolas P; Lamata, Pablo; Nordsletten, David A

    2015-12-01

    Pressure difference is an accepted clinical biomarker for cardiovascular disease conditions such as aortic coarctation. Currently, measurements of pressure differences in the clinic rely on invasive techniques (catheterization), prompting development of non-invasive estimates based on blood flow. In this work, we propose a non-invasive estimation procedure deriving pressure difference from the work-energy equation for a Newtonian fluid. Spatial and temporal convergence is demonstrated on in silico Phase Contrast Magnetic Resonance Image (PC-MRI) phantoms with steady and transient flow fields. The method is also tested on an image dataset generated in silico from a 3D patient-specific Computational Fluid Dynamics (CFD) simulation and finally evaluated on a cohort of 9 subjects. The performance is compared to existing approaches based on steady and unsteady Bernoulli formulations as well as the pressure Poisson equation. The new technique shows good accuracy, robustness to noise, and robustness to the image segmentation process, illustrating the potential of this approach for non-invasive pressure difference estimation. PMID:26409245

  5. Imaging molecular orbitals using photoionization

    NASA Astrophysics Data System (ADS)

    Santra, Robin

    2006-10-01

    The interpretation of a recent experiment using high-order harmonic generation [Itatani et al., Nature 432 (2004) 867] as a measurement of the highest occupied molecular orbital of a molecule is conceptually problematic, even if the independent-particle picture is taken seriously. Guided by the relationship between the amplitude for one-photon-induced electron emission and the electron-ion recombination amplitude in the three-step model of high-order harmonic generation, it is argued that synchrotron-based photoionization might be a superior approach to imaging molecular orbitals. Within the Hartree-Fock independent-particle picture, the molecular-frame photoelectron angular distributions, measured as a function of photon energy, could be used to reconstruct all orbitals occupied in the Hartree-Fock ground state of the molecule investigated. It is suggested that laser alignment techniques could be employed to facilitate the measurement of the molecular-frame photoelectron angular distributions.

  6. Cancer Stratification by Molecular Imaging

    PubMed Central

    Weber, Justus; Haberkorn, Uwe; Mier, Walter

    2015-01-01

    The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2). Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter), as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers. PMID:25749472

  7. Fatal brain gas embolism during non-invasive positive pressure ventilation

    PubMed Central

    Rivara, Claire B; Chevrolet, Jean-Claude; Gasche, Yvan; Charbonney, Emmanuel

    2008-01-01

    Gas embolism is a dreaded complication following invasive medical procedures, traumatic lung injury and decompression accidents. We report a case of fatal gas embolism following the use of non-invasive ventilation (NIV) with bilevel positive airway pressure (BiPAP). The patient initially underwent left bronchial artery embolisation for massive haemoptysis in the context of severe tuberculotic sequels. Under NIV and after heavy coughing he became hemiparetic and his level of consciousness suddenly dropped. Computed tomography of the brain showed multiple air embolism and ischaemic lesions were confirmed by magnetic resonance imaging. Echocardiographic investigations showed no intracardiac defect. Vasculo-pulmonary abnormalities in the context of heavy coughing and non-invasive ventilation may have played a major role in the occurrence of this event. New neurological events in a patient with tuberculotic sequels or any known vascular pulmonary abnormalities and NIV should raise the suspicion of brain gas embolism. PMID:21716825

  8. Non-invasive determination of the complete elastic moduli of spider silks

    NASA Astrophysics Data System (ADS)

    Koski, Kristie J.; Akhenblit, Paul; McKiernan, Keri; Yarger, Jeffery L.

    2013-03-01

    Spider silks possess nature’s most exceptional mechanical properties, with unrivalled extensibility and high tensile strength. Unfortunately, our understanding of silks is limited because the complete elastic response has never been measured—leaving a stark lack of essential fundamental information. Using non-invasive, non-destructive Brillouin light scattering, we obtain the entire stiffness tensors (revealing negative Poisson’s ratios), refractive indices, and longitudinal and transverse sound velocities for major and minor ampullate spider silks: Argiope aurantia, Latrodectus hesperus, Nephila clavipes, Peucetia viridans. These results completely quantify the linear elastic response for all possible deformation modes, information unobtainable with traditional stress-strain tests. For completeness, we apply the principles of Brillouin imaging to spatially map the elastic stiffnesses on a spider web without deforming or disrupting the web in a non-invasive, non-contact measurement, finding variation among discrete fibres, junctions and glue spots. Finally, we provide the stiffness changes that occur with supercontraction.

  9. Non-invasive determination of the complete elastic moduli of spider silks.

    PubMed

    Koski, Kristie J; Akhenblit, Paul; McKiernan, Keri; Yarger, Jeffery L

    2013-03-01

    Spider silks possess nature's most exceptional mechanical properties, with unrivalled extensibility and high tensile strength. Unfortunately, our understanding of silks is limited because the complete elastic response has never been measured-leaving a stark lack of essential fundamental information. Using non-invasive, non-destructive Brillouin light scattering, we obtain the entire stiffness tensors (revealing negative Poisson's ratios), refractive indices, and longitudinal and transverse sound velocities for major and minor ampullate spider silks: Argiope aurantia, Latrodectus hesperus, Nephila clavipes, Peucetia viridans. These results completely quantify the linear elastic response for all possible deformation modes, information unobtainable with traditional stress-strain tests. For completeness, we apply the principles of Brillouin imaging to spatially map the elastic stiffnesses on a spider web without deforming or disrupting the web in a non-invasive, non-contact measurement, finding variation among discrete fibres, junctions and glue spots. Finally, we provide the stiffness changes that occur with supercontraction. PMID:23353627

  10. Non-invasive subcutaneous fat reduction: a review.

    PubMed

    Kennedy, J; Verne, S; Griffith, R; Falto-Aizpurua, L; Nouri, K

    2015-09-01

    The risks, financial costs and lengthy downtime associated with surgical procedures for fat reduction have led to the development of a number of non-invasive techniques. Non-invasive body contouring now represents the fastest growing area of aesthetic medicine. There are currently four leading non-invasive techniques for reducing localized subcutaneous adipose tissue: low-level laser therapy (LLLT), cryolipolysis, radio frequency (RF) and high-intensity focused ultrasound (HIFU). To review and compare leading techniques and clinical outcomes of non-invasive subcutaneous fat reduction. The terms 'non-invasive', 'low-level laser', 'cryolipolysis', 'ultrasound' and 'radio frequency' were combined with 'lipolysis', 'fat reduction' or 'body contour' during separate searches in the PubMed database. We identified 31 studies (27 prospective clinical studies and four retrospective chart reviews) with a total of 2937 patients that had been treated with LLLT (n = 1114), cryolipolysis (n = 706), HIFU (n = 843) or RF (n = 116) or other techniques (n = 158) for fat reduction or body contouring. A majority of these patients experienced significant and satisfying results without any serious adverse effects. The studies investigating these devices have all varied in treatment regimen, body locations, follow-up times or outcome operationalization. Each technique differs in offered advantages and severity of adverse effects. However, multiple non-invasive devices are safe and effective for circumferential reduction in local fat tissue by 2 cm or more across the abdomen, hips and thighs. Results are consistent and reproducible for each device and none are associated with any serious or permanent adverse effects. PMID:25664493

  11. Non-invasive assessment of bone quality.

    PubMed

    Matsubara, M; Nakamura, K; Morita, S; Kashima, I

    1999-12-01

    A morphological filter and pipeline analysis was applied to computed radiographs (CR) to abstract the geometrical characteristics of the trabecular pattern and to analyze bone mechanical properties. By applying a morphological filter to the CR images, trabecular patterns were divided into 8 subset groups (n=O through 7) by the trabecular thickness. Sumset images were also derived from the thicker trabeculae group (n=2-5, 3-6, and 4-7) to examine the criteria relating the percentage of thicker trabeculae to the strength of the bone. A method to analyze the bone mechanical properties was developed, based on the hypothesis that data of connective line segments were loaded mechanically. By this method, trabeculae were analyzed in the fifth lumbar vertebrae from etidronic acid-treated and non-treated ovariectomized osteoporosis rat models, and in human third lumbar vertebrae. Consequently, it was shown that total loss of bone mass accompanied a reduction of consecutive trabecular number in the rat osteoporosis model, especially in parts of the bone having thick trabeculae. The reduction in number of connective trabeculae, from one cortical side to the other, occurred at a similar rate, along both the craniocaudal and anteroposterior axes in the vertebral bodies of the experimental osteoporosis rats. In the dynamic study with human third vertebral blocks, no significant correlation was observed between the bone mineral density of the bone specimens and their ultimate strength (R2=0.093). In contrast, the abstracted percentage of thicker trabeculae, derived from the sumset (n=2-5) images, showed a strong correlation with bony mechanical properties (Young's modulus: R2=0.915, maximum point load: R2=0.815). The result calculated by this methodology can serve as an excellent index to indicate bone strength under non-destructive, living conditions. PMID:12160254

  12. An Acetone Nanosensor For Non-invasive Diabetes Detection

    NASA Astrophysics Data System (ADS)

    Wang, L.; Yun, X.; Stanacevic, M.; Gouma, P. I.

    2009-05-01

    Diabetes is a most common disease worldwide. Acetone in exhaled breath is a known biomarker of Type- 1 diabetes. An exhaled breath analyzer has been developed with the potential to diagnose diabetes as a non-invasive alternative of the currently used blood-based diagnostics. This device utilizes a chemiresistor based on ferroelectric tungsten oxide nanoparticles and detects acetone selectively in breath-simulated media. Real-time monitoring of the acetone concentration is feasible, potentially making this detector a revolutionary, non- invasive, diabetes diagnostic tool.

  13. Non-invasive brain stimulation in early rehabilitation after stroke.

    PubMed

    Blesneag, A V; Popa, L; Stan, A D

    2015-01-01

    The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed. PMID:26361512

  14. Molecular Imaging of Pituitary Pathology.

    PubMed

    de Herder, Wouter W

    2016-01-01

    The presence of large numbers and/or the high affinity of dopamine D2 and/or somatostatin receptors on pituitary adenomas may enable their visualization with radionuclide-coupled receptor agonists or antagonists. However, the role of these imaging modalities in the differential diagnosis of or therapeutic purposes for pituitary lesions is very limited. Only in very specific cases might these molecular imaging techniques become helpful. These include the differential diagnosis of pituitary lesions, ectopic production of pituitary hormones, such as adrenocorticotrophic hormone, growth hormone (GH) or their releasing hormones (corticotropin-releasing hormone and GH-releasing hormone), and the localization of metastases from pituitary carcinomas. PMID:27002335

  15. Validation of a non-invasive arterial monitor GATE model for PET

    NASA Astrophysics Data System (ADS)

    Giansiracusa, P. J.; Peake, D. J.; Sobott, B. A.; O'Keefe, G.; Rassool, R. P.

    2014-02-01

    The Non-Invasive Arterial Monitor (NIAM3) is an SiPM based detector system designed for calibrating Positron-Emission Tomography (PET) images without invasive blood sampling. By imaging the radial and ulnar arteries in the wrist directly with a custom built PET system the resultant PET images can be calibrated. An integral step in the development of a complex detector system is the creation of a model which accurately reflects the physical reality being studied. This paper describes the development of a simulation for NIAM which shows good agreement between the model and physical detector setup.

  16. Advances in multimodality molecular imaging

    PubMed Central

    Zaidi, Habib; Prasad, Rameshwar

    2009-01-01

    Multimodality molecular imaging using high resolution positron emission tomography (PET) combined with other modalities is now playing a pivotal role in basic and clinical research. The introduction of combined PET/CT systems in clinical setting has revolutionized the practice of diagnostic imaging. The complementarity between the intrinsically aligned anatomic (CT) and functional or metabolic (PET) information provided in a “one-stop shop” and the possibility to use CT images for attenuation correction of the PET data has been the driving force behind the success of this technology. On the other hand, combining PET with Magnetic Resonance Imaging (MRI) in a single gantry is technically more challenging owing to the strong magnetic fields. Nevertheless, significant progress has been made resulting in the design of few preclinical PET systems and one human prototype dedicated for simultaneous PET/MR brain imaging. This paper discusses recent advances in PET instrumentation and the advantages and challenges of multimodality imaging systems. Future opportunities and the challenges facing the adoption of multimodality imaging instrumentation will also be addressed. PMID:20098557

  17. Non-invasive Thrombolysis using Microtripsy: A Parameter Study

    PubMed Central

    Zhang, Xi; Jin, Lifang; Vlaisavljevich, Eli; Owens, Gabe E.; Gurm, Hitinder S.; Cain, Charles A.; Xu, Zhen

    2016-01-01

    Histotripsy fractionates soft tissue by well-controlled acoustic cavitation using microsecond-long, high-intensity ultrasound pulses. The feasibility of using histotripsy as a non-invasive, drug-free, and image-guided thrombolysis method has been shown previously. A new histotripsy approach, termed Microtripsy, has recently been investigated for the thrombolysis application to improve treatment accuracy and avoid potential vessel damage. In this study, we investigated the effects of pulse repetition frequency (PRF) on microtripsy thrombolysis. Microtripsy thrombolysis treatments using different PRFs (5, 50, and 100 Hz) and doses (20, 50, and 100 pulses) were performed on blood clots in an in vitro vessel flow model. To quantitatively evaluate the microtripsy thrombolysis effect, the location of focal cavitation, the incident rate of pre-focal cavitation on the vessel wall, the size and location of the resulting flow channel, and the generated clot debris particles were measured. The results demonstrated that focal cavitation was always well-confined in the vessel lumen without contacting the vessel wall for all PRFs. Pre-focal cavitation on the front vessel wall was never observed at 5Hz PRF, but occasionally observed at PRFs of 50 Hz (1.2%) and 100 Hz (5.4%). However, the observed pre-focal cavitation was weak and didn’t significantly impact the focal cavitation. Results further demonstrated that, although the extent of clot fractionation per pulse was the highest at 5 Hz PRF at the beginning of treatment (<20 pulses), 100 Hz PRF generated the largest flow channels with a much shorter treatment time. Finally, results showed fewer large debris particles were generated at a higher PRF. Overall, the results of this study suggest that a higher PRF (50 or 100 Hz) may be a better choice for microtripsy thrombolysis to use clinically due to the larger resulting flow channel, shorter treatment time, and smaller debris particles. PMID:26670850

  18. Non-invasive optical characterization of biomaterial mineralization.

    PubMed

    Gupta, Sharad; Hunter, Martin; Cebe, Peggy; Levitt, Jonathan M; Kaplan, David L; Georgakoudi, Irene

    2008-05-01

    Current approaches to study biomaterial mineralization are invasive and prevent dynamic characterization of this process within the same sample. Polarized light scattering spectroscopy (LSS) may offer a non-invasive alternative for assessing the levels of mineralization as well as some aspects of the organization of the mineral deposits. Specifically, we used LSS to characterize the formation of hydroxyapatite deposits on three types of silk films (water-annealed, methanol-treated and polyaspartic acid (PAA)-mixed) following 1, 3, 5 and 7 cycles of mineralization. We found that the total light scattering intensity provided a quantitative measure of the degree of mineralization as confirmed by thermal gravimetric analysis (TGA). The PAA-mixed silk films yielded the highest level of mineral deposition and the water-annealed ones the least, consistent with the beta sheet content of the films prior to the onset of mineralization. The wavelength dependence of the singly backscattered light was consistent with a self-affine fractal morphology of the deposited films within scales in the range of 150-300nm; this was confirmed by Fourier analysis of scanning electron microscopy (SEM) images of the corresponding films. The deposits of minerals in the water-annealed films were predominantly flake-like, with positively correlated density fluctuations (Hurst parameter, H>0.5), whereas methanol-treated and PAA-mixed silk films resulted in densely-packed, bulk mineral deposits with negatively correlated density fluctuations (H<0.5). Therefore, LSS could serve as a valuable tool for understanding the role of biomaterial properties in mineral formation, and, ultimately, for optimizing biomaterial designs that yield mineral deposits with the desired organization. PMID:18313137

  19. The Book of Kells: a non-invasive MOLAB investigation by complementary spectroscopic techniques.

    PubMed

    Doherty, B; Daveri, A; Clementi, C; Romani, A; Bioletti, S; Brunetti, B; Sgamellotti, A; Miliani, C

    2013-11-01

    This paper highlights the efficacy of non-invasive portable spectroscopy for assessing the execution technique and constituent materials in one of the most important medieval manuscripts, the Book of Kells. An aimed campaign of in situ measurements by the MObile LABoratory (MOLAB) has analyzed its elemental composition and vibrational and electronic molecular properties. The ample analytical toolbox has afforded complementary diagnostic information of the pigment palette permitting the characterization of both inorganic and organic materials as pigments and dyes in the white, purple, blue, red, orange, green and black areas. In particular, the novel widespread use of calcinated gypsum (anhydrite) as both a white pigment and in correlation to the organic dyes in this manuscript has been noted. The non-invasive identification of the organic dye orchil is significant considering its rare non invasive detection in medieval manuscripts. Finally the occurrence of particular alterations of the organic black areas giving rise to calcium carboxylate and calcium oxalate has been specifically highlighted. Importantly, this work elaborates complex aspects of the employed painting materials which have given rise to numerous significant points of interest for a more elaborate understanding of this Irish treasure. PMID:23850791

  20. The Book of Kells: A non-invasive MOLAB investigation by complementary spectroscopic techniques

    NASA Astrophysics Data System (ADS)

    Doherty, B.; Daveri, A.; Clementi, C.; Romani, A.; Bioletti, S.; Brunetti, B.; Sgamellotti, A.; Miliani, C.

    2013-11-01

    This paper highlights the efficacy of non-invasive portable spectroscopy for assessing the execution technique and constituent materials in one of the most important medieval manuscripts, the Book of Kells. An aimed campaign of in situ measurements by the MObile LABoratory (MOLAB) has analyzed its elemental composition and vibrational and electronic molecular properties. The ample analytical toolbox has afforded complementary diagnostic information of the pigment palette permitting the characterization of both inorganic and organic materials as pigments and dyes in the white, purple, blue, red, orange, green and black areas. In particular, the novel widespread use of calcinated gypsum (anhydrite) as both a white pigment and in correlation to the organic dyes in this manuscript has been noted. The non-invasive identification of the organic dye orchil is significant considering its rare non invasive detection in medieval manuscripts. Finally the occurrence of particular alterations of the organic black areas giving rise to calcium carboxylate and calcium oxalate has been specifically highlighted. Importantly, this work elaborates complex aspects of the employed painting materials which have given rise to numerous significant points of interest for a more elaborate understanding of this Irish treasure.

  1. Molecular Imaging of Neuroendocrine Tumors

    PubMed Central

    Carrasquillo, Jorge A.; Chen, Clara C.

    2014-01-01

    Neuroendocrine tumors (NET) are a heterogeneous group of tumors that arise from neuroendocrine cells. These tumors may arise from various organs, including lung, thymus, thyroid, stomach, duodenum, small bowel, large bowel, appendix, pancreas, adrenal, and skin. Most are well differentiated and have the ability to produce biogenic amines and various hormones. NET usually occur sporadically but they also be associated with various familial syndromes. For the vast majority of NET, surgical resection is the treatment of choice whenever feasible. Localization of NET prior to surgery and for staging and follow-up relies on both anatomic and functional imaging modalities. In fact, the unique secretory characteristics of these tumors lend themselves to imaging by molecular imaging modalities, which can target specific metabolic pathways or receptors. Neuroendocrine cells have a variety of such target receptors and pathways for which radiopharmaceuticals have been developed, including [123I/131I]-metaiodobenzylguanidine (MIBG), [ 111In]pentetreotide, [68Ga] somatostatin analogs, [18F] fluorodeoxyglucose (FDG), [11C/18F] dihydroxyphenylalanine (DOPA), [11C] 5-hydroxytryptophan (5-HTP) 99mTc pentavalent dimercaptosuccinic acid ([99mTc] (V) DMSA, and [18F] fluorodopamine (FDA). Here, we review the molecular imaging approaches for NET using various radiopharmaceuticals. PMID:21167384

  2. Molecular Imaging of Prostate Cancer.

    PubMed

    Wibmer, Andreas G; Burger, Irene A; Sala, Evis; Hricak, Hedvig; Weber, Wolfgang A; Vargas, Hebert Alberto

    2016-01-01

    Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls. PMID:26587888

  3. Non-invasive assessment of liver fibrosis

    PubMed Central

    Papastergiou, Vasilios; Tsochatzis, Emmanuel; Burroughs, Andrew K.

    2012-01-01

    The presence and degree of hepatic fibrosis is crucial in order to make therapeutic decisions and predict clinical outcomes. Currently, the place of liver biopsy as the standard of reference for assessing liver fibrosis has been challenged by the increasing awareness of a number of drawbacks related to its use (invasiveness, sampling error, inter-/intraobserver variability). In parallel with this, noninvasive assessment of liver fibrosis has experienced explosive growth in recent years and a wide spectrum of noninvasive methods ranging from serum assays to imaging techniques have been developed. Some are validated methods, such as the Fibrotest/ Fibrosure and transient elastography in Europe, and are gaining a growing role in routine clinical practice, especially in chronic hepatitis C. Large-scale validation is awaited in the setting of other chronic liver diseases. However, noninvasive tests used to detect significant fibrosis and cirrhosis, the two major clinical endpoints, are not yet at a level of performance suitable for routine diagnostic tests, and there is still no perfect surrogate or method able to completely replace an optimal liver biopsy. This article aims to review current noninvasive tests for the assessment of liver fibrosis and the perspectives for their rational use in clinical practice. PMID:24714123

  4. Non-invasive assessment of liver fibrosis.

    PubMed

    Papastergiou, Vasilios; Tsochatzis, Emmanuel; Burroughs, Andrew K

    2012-01-01

    The presence and degree of hepatic fibrosis is crucial in order to make therapeutic decisions and predict clinical outcomes. Currently, the place of liver biopsy as the standard of reference for assessing liver fibrosis has been challenged by the increasing awareness of a number of drawbacks related to its use (invasiveness, sampling error, inter-/intraobserver variability). In parallel with this, noninvasive assessment of liver fibrosis has experienced explosive growth in recent years and a wide spectrum of noninvasive methods ranging from serum assays to imaging techniques have been developed. Some are validated methods, such as the Fibrotest/ Fibrosure and transient elastography in Europe, and are gaining a growing role in routine clinical practice, especially in chronic hepatitis C. Large-scale validation is awaited in the setting of other chronic liver diseases. However, noninvasive tests used to detect significant fibrosis and cirrhosis, the two major clinical endpoints, are not yet at a level of performance suitable for routine diagnostic tests, and there is still no perfect surrogate or method able to completely replace an optimal liver biopsy. This article aims to review current noninvasive tests for the assessment of liver fibrosis and the perspectives for their rational use in clinical practice. PMID:24714123

  5. Non-invasive activation of optogenetic actuators

    NASA Astrophysics Data System (ADS)

    Birkner, Elisabeth; Berglund, Ken; Klein, Marguerita E.; Augustine, George J.; Hochgeschwender, Ute

    2014-03-01

    The manipulation of genetically targeted neurons with light (optogenetics) continues to provide unprecedented avenues into studying the function of the mammalian brain. However, potential translation into the clinical arena faces a number of significant hurdles, foremost among them the need for insertion of optical fibers into the brain to deliver light to opsins expressed on neuronal membranes. In order to overcome these hardware-related problems, we have developed an alternative strategy for delivering light to opsins which does not involve fiber implants. Rather, the light is produced by a protein, luciferase, which oxidizes intravenously applied substrate, thereby emitting bioluminescence. In proof-ofprinciple studies employing a fusion protein of a light-generating luciferase to a light-sensing opsin (luminopsin), we showed that light emitted by Gaussia luciferase is indeed able to activate channelrhodopsin, allowing modulation of neuronal activity when expressed in cultured neurons. Here we assessed applicability of the concept in vivo in mice expressing luminopsins from viral vectors and from genetically engineered transgenes. The experiments demonstrate that intravenously applied substrate reaches neurons in the brain, causing the luciferase to produce bioluminescence which can be imaged in vivo, and that activation of channelrhodopsin by bioluminescence is sufficient to affect behavior. Further developments of such technology based on combining optogenetics with bioluminescence - i.e. combining lightsensing molecules with biologically produced light through luciferases - should bring optogenetics closer to clinical applications.

  6. Non-invasive monitoring of pulmonary artery pressure from timing information by EIT: experimental evaluation during induced hypoxia.

    PubMed

    Proença, Martin; Braun, Fabian; Solà, Josep; Adler, Andy; Lemay, Mathieu; Thiran, Jean-Philippe; Rimoldi, Stefano F

    2016-06-01

    Monitoring of pulmonary artery pressure (PAP) in pulmonary hypertensive patients is currently limited to invasive solutions. We investigate a novel non-invasive approach for continuous monitoring of PAP, based on electrical impedance tomography (EIT), a safe, low-cost and non-invasive imaging technology. EIT recordings were performed in three healthy subjects undergoing hypoxia-induced PAP variations. The pulmonary pulse arrival time (PAT), a timing parameter physiologically linked to the PAP, was automatically calculated from the EIT signals. Values were compared to systolic PAP values from Doppler echocardiography, and yielded strong correlation scores ([Formula: see text]) for all three subjects. Results suggest the feasibility of non-invasive, unsupervised monitoring of PAP. PMID:27212013

  7. Reliable, Low Mass, Non-Invasive Pressure Transducers

    NASA Technical Reports Server (NTRS)

    Hartley, F.; Tovey, M.

    1999-01-01

    Mass is a major driver for future spacecraft and missions exposed to high radiation levels (i.e. Europa Orbiter) present even more challenge. A variety of non-invasive measurement techniques are in development that enables determination of pressures within a propulsion network.

  8. Method for non-invasive detection of ocular melanoma

    DOEpatents

    Lambrecht, Richard M.; Packer, Samuel

    1984-01-01

    There is described an apparatus and method for diagnosing ocular cancer that is both non-invasive and accurate which comprises two radiation detectors positioned before each of the patient's eyes which will measure the radiation level produced in each eye after the administration of a tumor-localizing radiopharmaceutical such as gallium-67.

  9. Method for non-invasive detection of ocular melanoma

    DOEpatents

    Lambrecht, R.M.; Packer, S.

    1984-10-30

    An apparatus and method is disclosed for diagnosing ocular cancer that is both non-invasive and accurate. The apparatus comprises two radiation detectors positioned before each of the patient's eyes which will measure the radiation level produced in each eye after the administration of a tumor-localizing radiopharmaceutical such as gallium-67. 2 figs.

  10. Non-invasive Prediction of Pork Loin Tenderness

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present experiment was conducted to develop a non-invasive method to predict tenderness of pork loins. Boneless pork loins (n = 901) were evaluated either on line on the loin boning and trimming line of large-scale commercial plants (n = 465) or at the U.S. Meat Animal Research Center abattoir ...

  11. NON-INVASIVE NEUROTOXICITY ASSAY USING LARVAL MEDAKA

    EPA Science Inventory

    We present a method for non-invasive electrophysiological analysis of rapid escape responses in intact, freely behaving larval medaka (Oryzias latipes) before and after short-term exposure to environmental toxicants. ecordings are obtained as a larval medaka swims in a small cham...

  12. Non-invasive treatment options for focal cortical dysplasia

    PubMed Central

    WANG, TING-TING; ZHOU, DONG

    2016-01-01

    Focal cortical dysplasia (FCD) presents a strong clinical challenge especially for the treatment of the associated epilepsy. Epilepsy in FCD is often treatment-resistant and constitutes 50% of treatment-resistant cases. Antiepileptic drugs (AEDs) have been widely used in the treatment of FCD. However, evidence to suggest their specific effect on the treatment of FCD remains to be established. In view of this resistance, several alternative treatments have been suggested. Although treatment currently involves surgical management, non-invasive treatments have been identified. The aim of the present review, was to assess non-invasive management strategies including, i) mammalian target of rapamycin (mTOR) inhibitors, ii) ketogenic diet (KD), and iii) vagus nerve stimulation (VNS). In addition, we discussed the literature available regarding the use of AEDs in FCD. Experiments conducted with mammals detailing rapamycin gene mutations in FCD have produced vital information for exploring treatment options using mTOR inhibitors. Of note is the importance of KD in children with FCD. This diet has been shown to modify disease progression by attenuating chromatin modification, a master regulator for gene expression and functional adaptation of the cell. FCD has also been studied widely with neurostimulation techniques. The outcomes of these techniques have been found to be variable. For widespread dysplasias, VNS has been shown to produce responder rates of >50%. Nevertheless, non-invasive cranial nerve stimulation techniques such as transcutaneous VNS and non-invasive VNS are gaining better patient compatibility, albeit their efficacy remains to be established. PMID:27168769

  13. Non-invasive in vivo measurement of macular carotenoids

    NASA Technical Reports Server (NTRS)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2009-01-01

    A non-invasive in vivo method for assessing macular carotenoids includes performing Optical Coherence Tomography (OCT) on a retina of a subject. A spatial representation of carotenoid levels in the macula based on data from the OCT of the retina can be generated.

  14. Eyeblink Conditioning: A Non-Invasive Biomarker for Neurodevelopmental Disorders

    ERIC Educational Resources Information Center

    Reeb-Sutherland, Bethany C.; Fox, Nathan A.

    2015-01-01

    Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition,…

  15. Non-invasive method of measuring cerebral spinal fluid pressure

    NASA Technical Reports Server (NTRS)

    Borchert, Mark S. (Inventor); Lambert, James L. (Inventor)

    2000-01-01

    The invention provides a method of non-invasively determining intracranial pressure from measurements of an eye. A parameter of an optic nerve of the eye is determined, along with an intraocular pressure of the eye. The intracranial pressure may be determined from the intraocular pressure and the parameter.

  16. Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

    PubMed Central

    Chin, Jun L.; Pavlides, Michael; Moolla, Ahmad; Ryan, John D.

    2016-01-01

    Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID:27378924

  17. A non-invasive head-holding device for chronic neural recordings in awake behaving monkeys

    PubMed Central

    Amemori, Satoko; Amemori, Ken-ichi; Cantor, Margaret L.; Graybiel, Ann M.

    2014-01-01

    Background We have developed a novel head-holding device for behaving non-human primates that affords stability suitable for reliable chronic electrophysiological recording experiments. The device is completely non-invasive, and thus avoids the risk of infection and other complications that can occur with the use of conventional, surgically implanted head-fixation devices. New method The device consists of a novel non-invasive head mold and bar clamp holder, and is customized to the shape of each monkey’s head. The head-holding device that we introduce, combined with our recording system and reflection-based eye-tracking system, allows for chronic behavioral experiments and single-electrode or multi-electrode recording, as well as manipulation of brain activity. Results and comparison with existing methods With electrodes implanted chronically in multiple brain regions, we could record neural activity from cortical and subcortical structures with stability equal to that recorded with conventional head-post fixation. Consistent with the non-invasive nature of the device, we could record neural signals for more than two years with a single implant. Importantly, the monkeys were able to hold stable eye fixation positions while held by this device, demonstrating the possibility of analyzing eye movement data with only the gentle restraint imposed by the non-invasive head-holding device. Conclusions We show that the head-holding device introduced here can be extended to the head holding of smaller animals, and note that it could readily be adapted for magnetic resonance brain imaging over extended periods of time. PMID:25448381

  18. Non-invasive, non-radiological quantification of anteroposterior knee joint ligamentous laxity

    PubMed Central

    Russell, D. F.; Deakin, A. H.; Fogg, Q. A.; Picard, F.

    2013-01-01

    Objectives We performed in vitro validation of a non-invasive skin-mounted system that could allow quantification of anteroposterior (AP) laxity in the outpatient setting. Methods A total of 12 cadaveric lower limbs were tested with a commercial image-free navigation system using trackers secured by bone screws. We then tested a non-invasive fabric-strap system. The lower limb was secured at 10° intervals from 0° to 60° of knee flexion and 100 N of force was applied perpendicular to the tibia. Acceptable coefficient of repeatability (CR) and limits of agreement (LOA) of 3 mm were set based on diagnostic criteria for anterior cruciate ligament (ACL) insufficiency. Results Reliability and precision within the individual invasive and non-invasive systems was acceptable throughout the range of flexion tested (intra-class correlation coefficient 0.88, CR 1.6 mm). Agreement between the two systems was acceptable measuring AP laxity between full extension and 40° knee flexion (LOA 2.9 mm). Beyond 40° of flexion, agreement between the systems was unacceptable (LOA > 3 mm). Conclusions These results indicate that from full knee extension to 40° flexion, non-invasive navigation-based quantification of AP tibial translation is as accurate as the standard validated commercial system, particularly in the clinically and functionally important range of 20° to 30° knee flexion. This could be useful in diagnosis and post-operative evaluation of ACL pathology. Cite this article: Bone Joint Res 2013;2:233–7. PMID:24184443

  19. Development and validation of a MRgHIFU non-invasive tissue acoustic property estimation technique.

    PubMed

    Johnson, Sara L; Dillon, Christopher; Odéen, Henrik; Parker, Dennis; Christensen, Douglas; Payne, Allison

    2016-11-01

    MR-guided high-intensity focussed ultrasound (MRgHIFU) non-invasive ablative surgeries have advanced into clinical trials for treating many pathologies and cancers. A remaining challenge of these surgeries is accurately planning and monitoring tissue heating in the face of patient-specific and dynamic acoustic properties of tissues. Currently, non-invasive measurements of acoustic properties have not been implemented in MRgHIFU treatment planning and monitoring procedures. This methods-driven study presents a technique using MR temperature imaging (MRTI) during low-temperature HIFU sonications to non-invasively estimate sample-specific acoustic absorption and speed of sound values in tissue-mimicking phantoms. Using measured thermal properties, specific absorption rate (SAR) patterns are calculated from the MRTI data and compared to simulated SAR patterns iteratively generated via the Hybrid Angular Spectrum (HAS) method. Once the error between the simulated and measured patterns is minimised, the estimated acoustic property values are compared to the true phantom values obtained via an independent technique. The estimated values are then used to simulate temperature profiles in the phantoms, and compared to experimental temperature profiles. This study demonstrates that trends in acoustic absorption and speed of sound can be non-invasively estimated with average errors of 21% and 1%, respectively. Additionally, temperature predictions using the estimated properties on average match within 1.2 °C of the experimental peak temperature rises in the phantoms. The positive results achieved in tissue-mimicking phantoms presented in this study indicate that this technique may be extended to in vivo applications, improving HIFU sonication temperature rise predictions and treatment assessment. PMID:27441427

  20. A short-wavelength infrared emitting multimodal probe for non-invasive visualization of phagocyte cell migration in living mice.

    PubMed

    Tsukasaki, Y; Komatsuzaki, A; Mori, Y; Ma, Q; Yoshioka, Y; Jin, T

    2014-11-28

    For the non-invasive visualization of cell migration in deep tissues, we synthesized a short-wavelength infrared (SWIR) emitting multimodal probe that contains PbS/CdS quantum dots, rhodamine 6G and iron oxide nanoparticles. This probe enables multimodal (SWIR fluorescence/magnetic resonance) imaging of phagocyte cell migration in living mice. PMID:25296382

  1. Companion Diagnostics and Molecular Imaging.

    PubMed

    Puranik, Ameya D; Kulkarni, Harshad R; Baum, Richard P

    2015-01-01

    Companion diagnostics (CDx) is a positive attempt in the direction of improving the drug development process, especially in the field of oncology, with the advent of newer targeted therapies. It helps the oncologist in deciding the choice of treatment for the individual patient. The role of CDx assays has attracted the attention of regulators, and especially the US Food and Drug Administration developed regulatory strategies for CDx and the drug-diagnostic codevelopment project. For an increasing number of cancer patients, the treatment selection will depend on the result generated by a CDx assay, and consequently this type of assay has become critical for the care and safety of the patients. In addition to the assay-based approach, molecular imaging with its ability to image at the genetic and receptor level has made foray into the field of drug development and personalized medicine. We shall review these aspects of CDx, with special focus on molecular imaging and the upcoming concept of Theranostics. PMID:26049701

  2. Molecular Imaging of Prostate Cancer

    PubMed Central

    Fox, Josef J.; Schöder, Heiko; Larson, Steven M.

    2015-01-01

    Purpose of review Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Recent findings Several PET tracers are active in early and late stage prostate cancer in humans. F18-FDG, C11/F18-choline and F18-sodium fluoride (NaF) have been studied most extensively. There is a growing body of literature supporting to the utility of choline in early stage prostate cancer. FDG and NaF are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-Fluoro-dihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel AR-targeted therapies. Anti-PSMA PET tracers are in the early stages of clinical development. Summary Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer. PMID:22617062

  3. Transport and Non-Invasive Position Detection of Electron Beams from Laser-Plasma Accelerators

    SciTech Connect

    Osterhoff, Jens; Sokollik, Thomas; Nakamura, Kei; Bakeman, Michael; Weingartner, R; Gonsalves, Anthony; Shiraishi, Satomi; Lin, Chen; vanTilborg, Jeroen; Geddes, Cameron; Schroeder, Carl; Esarey, Eric; Toth, Csaba; DeSantis, Stefano; Byrd, John; Gruner, F; Leemans, Wim

    2011-07-20

    The controlled imaging and transport of ultra-relativistic electrons from laser-plasma accelerators is of crucial importance to further use of these beams, e.g. in high peak-brightness light sources. We present our plans to realize beam transport with miniature permanent quadrupole magnets from the electron source through our THUNDER undulator. Simulation results demonstrate the importance of beam imaging by investigating the generated XUV-photon flux. In addition, first experimental findings of utilizing cavity-based monitors for non-invasive beam-position measurements in a noisy electromagnetic laser-plasma environment are discussed.

  4. Transport and Non-Invasive Position Detection of Electron Beams from Laser-Plasma Accelerators

    SciTech Connect

    Osterhoff, J.; Nakamura, K.; Bakeman, M.; Gonsalves, A. J.; Shiraishi, S.; Lin, C.; Tilborg, J. van; Geddes, C. G. R.; Schroeder, C. B.; Esarey, E.; Toth, Cs.; De Santis, S.; Byrd, J. M.; Leemans, W. P.; Sokollik, T.; Weingartner, R.; Gruener, F.

    2010-11-04

    The controlled imaging and transport of ultra-relativistic electrons from laser-plasma accelerators is of crucial importance to further use of these beams, e.g. in high peak-brightness light sources. We present our plans to realize beam transport with miniature permanent quadrupole magnets from the electron source through our THUNDER undulator. Simulation results demonstrate the importance of beam imaging by investigating the generated XUV-photon flux. In addition, first experimental findings of utilizing cavity-based monitors for non-invasive beam-position measurements in a noisy electromagnetic laser-plasma environment are discussed.

  5. Molecular Imaging: Current Status and Emerging Strategies

    PubMed Central

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

    2011-01-01

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

  6. Recent advances in ophthalmic molecular imaging.

    PubMed

    Ramos de Carvalho, J Emanuel; Verbraak, Frank D; Aalders, Maurice C; van Noorden, Cornelis J; Schlingemann, Reinier O

    2014-01-01

    The aim of molecular imaging techniques is the visualization of molecular processes and functional changes in living animals and human patients before morphological changes occur at the cellular and tissue level. Ophthalmic molecular imaging is still in its infancy and has mainly been used in small animals for pre-clinical research. The goal of most of these pre-clinical studies is their translation into ophthalmic molecular imaging techniques in clinical care. We discuss various molecular imaging techniques and their applications in ophthalmology. PMID:24529711

  7. Determination of the thermal properties of leaves by non-invasive contact‑free laser probing.

    PubMed

    Buyel, J F; Gruchow, H M; Tödter, N; Wehner, M

    2016-01-10

    The thermal properties of materials provide valuable data for quality monitoring and the rational design of process steps where heating is required. Here we report a rapid, simple and reliable technique that determines the most important thermal properties of leaves, i.e. the specific heat capacity (cp) and thermal conductivity (λ). Such data are useful when leaves are heated during processing, e.g. for the precipitation of host cell proteins during the extraction of high-value products such as recombinant proteins produced by molecular farming. The cp of tobacco (Nicotiana tabacum) and Nicotiana benthamiana leaves was determined by infrared measurement of the temperature increase caused by a near-infrared laser pulse of defined length and intensity. We used the sample temperature profiles to calculate λ based on exponential fits of the temperature decline, taking convective heat transfer and thermal radiation into account. We found that the average cp was 3661 ± 323 J kg(-1) K(-1) (n=19) for tobacco and 2253 ± 285 J kg(-1) K(-1) (n=25) for N. benthamiana, whereas the average λ was 0.49 ± 0.13 (n=19) for tobacco and 0.41 ± 0.20 (n=25) Jm(-1) s(-1)K(-1) for N. benthamiana. These values are similar to those established for other plant species by photothermal imaging and other methods. The cp and λ values of leaves can be determined easily using our non-invasive method, which is therefore suitable for the in-line or at-line monitoring of plants, e.g. during the highly regulated production of biopharmaceutical proteins. PMID:26608794

  8. Skin rejuvenation with non-invasive pulsed electric fields.

    PubMed

    Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P; Albadawi, Hassan; Felix Broelsch, G; Watkins, Michael T; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C; Austen, William G; Yarmush, Martin L

    2015-01-01

    Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases. PMID:25965851

  9. Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

    PubMed Central

    Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm Jr., Martin C.; Austen Jr., William G.; Yarmush, Martin L.

    2015-01-01

    Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases. PMID:25965851

  10. Non-invasive microsensors for studying cell/tissue physiology

    NASA Astrophysics Data System (ADS)

    Vanegas, D. C.; Taguchi, M.; Chaturvedi, P.; Burrs, S.; McLamore, E. S.

    2013-05-01

    Non-invasive tools that allow real-time quantification of molecules relevant to metabolism, homeostasis, and cell signaling in cells and tissue are of great importance for studying physiology. Several microsensor technologies have been developed to monitor concentration of molecules such as ions, oxygen, electroactive molecules (e.g., nitric oxide, hydrogen peroxide), and biomolecules (e.g., sugars, hormones). The major challenges for microsensors are overcoming relatively low sensitivity and low signal-to-noise ratio. Modern approaches for enhancing microsensor performance focus on the incorporation of catalytic nanomaterials to increase sensitivity, reduce response time, and increase operating range. To improve signal-to-noise ratio, a non-invasive microsensor modality called self-referencing (SR) is being applied. The SR technique allows measurement of temporal and spatial transport dynamics at the cell, tissue, organ, and organismal level.

  11. Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

    NASA Astrophysics Data System (ADS)

    Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C., Jr.; Austen, William G., Jr.; Yarmush, Martin L.

    2015-05-01

    Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.

  12. Non invasive ventilation as an additional tool for exercise training.

    PubMed

    Ambrosino, Nicolino; Cigni, Paolo

    2015-01-01

    Recently, there has been increasing interest in the use of non invasive ventilation (NIV) to increase exercise capacity. In individuals with COPD, NIV during exercise reduces dyspnoea and increases exercise tolerance. Different modalities of mechanical ventilation have been used non-invasively as a tool to increase exercise tolerance in COPD, heart failure and lung and thoracic restrictive diseases. Inspiratory support provides symptomatic benefit by unloading the ventilatory muscles, whereas Continuous Positive Airway Pressure (CPAP) counterbalances the intrinsic positive end-expiratory pressure in COPD patients. Severe stable COPD patients undergoing home nocturnal NIV and daytime exercise training showed some benefits. Furthermore, it has been reported that in chronic hypercapnic COPD under long-term ventilatory support, NIV can also be administered during walking. Despite these results, the role of NIV as a routine component of pulmonary rehabilitation is still to be defined. PMID:25874110

  13. Label-free molecular imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Junqi; Li, Qi; Fu, Rongxin; Wang, Tongzhou; Wang, Ruliang; Huang, Guoliang

    2014-03-01

    Optical microscopy technology has achieved great improvements in the 20th century. The detection limit has reached about twenty nanometers (with near-field optics, STED, PALM and STORM). But in the application areas such as life science, medical science, clinical treatment and especially in vivo dynamic measurement, mutual restrictions still exist between numeric aperture/magnification and working distance, fluorescent dependent, and between resolution and frame rate/field size, etc. This paper explores a hyperspectral scanning super-resolution label free molecules imaging method based on the white light interferometry. The vertical detection resolution was approximate to 1 nm which is the thickness of a single molecular layer and dynamic measuring range of thickness reaches to 10 μm. The spectrum-shifting algorithm is developed for robust restructure of images when the pixels are overlapped. Micro-biochip with protein binding and DNA amplification could be detected by using this spectral scanning super-resolution molecules imaging in label free. This method has several advantages as following: Firstly, the decoding and detecting steps are combined into one step. It makes tests faster and easier. Secondly, we used thickness-coded, minimized chips instead of a large microarray chip to carry the probes. This accelerates the interaction of the biomolecules. Thirdly, since only one kind of probes are attached to our thickness-coded, minimized chip, users can only pick out the probes they are interested in for a test without wasting unnecessary probes and chips.

  14. SQUID magnetometry applied as non-invasive electroanalytic chemical technique

    SciTech Connect

    Jette, B.D.; MacVicar, M.L.A. )

    1991-03-01

    This paper reports on a SQUID magnetometer, employed as a highly sensitive ammeter, used to perform standard electroanalytic chemical measurements non- invasively. Specifically, the magnetic fields generated by the net ionic movement in the solution of a driven electrochemical system is detected by the gradiometer coils. The SQUID signal can then be compared to conventional current measurements. One such standard measurement investigated is Cyclic Voltametry (CV) which determines the I-V characteristics of an electrochemical system yielding critical kinetic parameters.

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

    PubMed Central

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

    2014-01-01

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

  16. Non invasive assessment of the human tear film dynamics.

    PubMed

    Ring, M H; Rabensteiner, D F; Horwath-Winter, J; Boldin, I; Schrödl, F; Reitsamer, H; Haslwanter, T

    2015-11-01

    Dry eye disease, or keratoconjunctivitis sicca, is a multifactorial syndrome with altered tear film homeostasis leading to ocular irritations. These alterations cause discomfort and stress for the patient, but only a few objective parameters allow for proper differential diagnosis into different subtypes of this condition. The mostly invasively performed standard assessment procedures for tear film diagnosis are manifold, but often correlate quite poorly with the subjectively reported symptoms. Due to the inherent limitations, e.g. the subjectivity of the commonly performed invasive tests, a number of devices have been developed to assess the human tear film non-invasively. Since the production, delivery, distribution and drainage of the tear film is a dynamic process, we have focused our review on non-invasive methods which are capable of continuous or repetitive observations of the tear film during an inter-blink interval. These dynamic methods include (1) Interferometry, (2) Pattern Projection, (3) Aberrometry, (4) Thermography; and (5) Evaporimetry. These techniques are discussed with respect to their diagnostic value, both for screening and differential diagnostic of Dry Eye Disease. Many of the parameters obtained from these tests have been shown to have the potential to reliably discriminate patients from healthy subjects, especially when the tests are performed automatically and objectively. The differentiation into subtypes based solely on a single, dynamic parameter may not be feasible, but the combination of non-invasively performed procedures may provide good discrimination results. PMID:26406882

  17. Non-invasive and in vivo assessment of osteoarthritic articular cartilage: a review on MRI investigations.

    PubMed

    Hani, Ahmad Fadzil Mohd; Kumar, Dileep; Malik, Aamir Saeed; Ahmad, Raja Mohd Kamil Raja; Razak, Ruslan; Kiflie, Azman

    2015-01-01

    Early detection of knee osteoarthritis (OA) is of great interest to orthopaedic surgeons, rheumatologists, radiologists, and researchers because it would allow physicians to provide patients with treatments and advice to slow the onset or progression of the disease. Early detection can be achieved by identifying early changes in selected features of degenerative articular cartilage (AC) using non-invasive imaging modalities. Magnetic resonance imaging (MRI) is becoming the standard for assessment of OA. The aim of this paper was to review the influence of MRI on the selection, detection, and measurement of AC features associated with early OA. Our review of the literature indicates that the changes associated with early OA are in cartilage thickness, cartilage volume, cartilage water content, and proteoglycan content that can be accurately, consistently, and non-invasively measured using MRI. Choosing an MR pulse sequence that provides the capability to assess cartilage physiology and morphology in a single acquisition and advanced multi-nuclei MRI is desirable. The results of the review indicate that using an ultra-high magnetic strength, MR imager does not affect early OA detection. In conclusion, MRI is currently the most suitable modality for early detection of knee OA, and future research should focus on the quantitative evaluation of early OA features using advances in MR hardware, software, and data processing with sophisticated image/pattern recognition techniques. PMID:24879325

  18. Deconstructing autofluorescence: non-invasive detection and monitoring of biochemistry in cells and tissues (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Goldys, Ewa M.; Gosnell, Martin E.; Anwer, Ayad G.; Cassano, Juan C.; Sue, Carolyn M.; Mahbub, Saabah B.; Pernichery, Sandeep M.; Inglis, David W.; Adhikary, Partho P.; Jazayeri, Jalal A.; Cahill, Michael A.; Saad, Sonia; Pollock, Carol; Sutton-Mcdowall, Melanie L.; Thompson, Jeremy G.

    2016-03-01

    Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous fluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from imaging of native fluorescence has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Multispectral intrinsic fluorescence imaging was applied to patient olfactory neurosphere-derived cells, cell model of a human metabolic disease MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like syndrome). By using an endogenous source of contrast, subtle metabolic variations have been detected between living cells in their full morphological context which made it possible to distinguish healthy from diseased cells before and after therapy. Cellular maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant cell subpopulations, in particular a subpopulation with compromised mitochondrial function. The versatility of our method is further illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent.

  19. Non-invasive cardiac mapping in clinical practice: Application to the ablation of cardiac arrhythmias.

    PubMed

    Dubois, Rémi; Shah, Ashok J; Hocini, Mélèze; Denis, Arnaud; Derval, Nicolas; Cochet, Hubert; Sacher, Frédéric; Bear, Laura; Duchateau, Josselin; Jais, Pierre; Haissaguerre, Michel

    2015-01-01

    Ten years ago, electrocardiographic imaging (ECGI) started to demonstrate its efficiency in clinical settings. The initial application to localize focal ventricular arrhythmias such as ventricular premature beats was probably the easiest to challenge and validates the concept. Our clinical experience in using this non-invasive mapping technique to identify the sources of electrical disorders and guide catheter ablation of atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beats) and ventricular pre-excitation (Wolff-Parkinson-White syndrome) is described here. PMID:26403066

  20. Non-invasive measurements of tissue hemodynamics with hybrid diffuse optical methods

    NASA Astrophysics Data System (ADS)

    Durduran, Turgut

    Diffuse optical techniques were used to measure hemodynamics of tissues non-invasively. Spectroscopy and tomography of the brain, muscle and implanted tumors were carried out in animal models and humans. Two qualitatively different methods, diffuse optical tomography and diffuse correlation tomography, were hybridized permitting simultaneous measurement of total hemoglobin concentration, blood oxygen saturation and blood flow. This combination of information was processed further to derive estimates of oxygen metabolism (e.g. CMRO 2) in tissue. The diffuse correlation measurements of blood flow were demonstrated in human tissues, for the first time, demonstrating continous, non-invasive imaging of oxygen metabolism in large tissue volumes several centimeters below the tissue surface. The bulk of these investigations focussed on cerebral hemodynamics. Extensive validation of this methodology was carried out in in vivo rat brain models. Three dimensional images of deep tissue hemodynamics in middle cerebral artery occlusion and cortical spreading depression (CSD) were obtained. CSD hemodynamics were found to depend strongly on partial pressure of carbon dioxide. The technique was then adapted for measurement of human brain. All optical spectroscopic measurements of CMRO2 during functional activation were obtained through intact human skull non-invasively. Finally, a high spatio-temporal resolution measurement of cerebral blood flow due to somatosensory cortex activation following electrical forepaw stimulation in rats was carried out with laser speckle flowmetry. New analysis methods were introduced for laser speckle flowmetry. In other organs, deep tissue hemodynamics were measured on human calf muscle during exercise and cuff-ischemia and were shown to have some clinical utility for peripheral vascular disease. In mice tumor models, the measured hemodynamics were shown to be predictive of photodynamic therapy efficacy, again suggesting promise of clinical utility

  1. Quantitative non-invasive cell characterisation and discrimination based on multispectral autofluorescence features

    PubMed Central

    Gosnell, Martin E.; Anwer, Ayad G.; Mahbub, Saabah B.; Menon Perinchery, Sandeep; Inglis, David W.; Adhikary, Partho P.; Jazayeri, Jalal A.; Cahill, Michael A.; Saad, Sonia; Pollock, Carol A.; Sutton-McDowall, Melanie L.; Thompson, Jeremy G.; Goldys, Ewa M.

    2016-01-01

    Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous autofluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from autofluorescence imaging has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent. Label-free classifications are validated by the analysis of Classification Determinant (CD) antigen expression. The versatility of our method is illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. PMID:27029742

  2. Non-invasive and non-destructive measurements of confluence in cultured adherent cell lines.

    PubMed

    Busschots, Steven; O'Toole, Sharon; O'Leary, John J; Stordal, Britta

    2015-01-01

    Many protocols used for measuring the growth of adherent monolayer cells in vitro are invasive, destructive and do not allow for the continued, undisturbed growth of cells within flasks. Protocols often use indirect methods for measuring proliferation. Microscopy techniques can analyse cell proliferation in a non-invasive or non-destructive manner but often use expensive equipment and software algorithms. In this method images of cells within flasks are captured by photographing under a standard inverted phase contract light microscope using a digital camera with a camera lens adaptor. Images are analysed for confluence using ImageJ freeware resulting in a measure of confluence known as an Area Fraction (AF) output. An example of the AF method in use on OVCAR8 and UPN251 cell lines is included. •Measurements of confluence from growing adherent cell lines in cell culture flasks is obtained in a non-invasive, non-destructive, label-free manner.•The technique is quick, affordable and eliminates sample manipulation.•The technique provides an objective, consistent measure of when cells reach confluence and is highly correlated to manual counting with a haemocytometer. The average correlation co-efficient from a Spearman correlation (n = 3) was 0.99 ± 0.008 for OVCAR8 (p = 0.01) and 0.99 ± 0.01 for UPN251 (p = 0.01) cell lines. PMID:26150966

  3. Quantitative non-invasive cell characterisation and discrimination based on multispectral autofluorescence features.

    PubMed

    Gosnell, Martin E; Anwer, Ayad G; Mahbub, Saabah B; Menon Perinchery, Sandeep; Inglis, David W; Adhikary, Partho P; Jazayeri, Jalal A; Cahill, Michael A; Saad, Sonia; Pollock, Carol A; Sutton-McDowall, Melanie L; Thompson, Jeremy G; Goldys, Ewa M

    2016-01-01

    Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous autofluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from autofluorescence imaging has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent. Label-free classifications are validated by the analysis of Classification Determinant (CD) antigen expression. The versatility of our method is illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. PMID:27029742

  4. Non-invasive and non-destructive measurements of confluence in cultured adherent cell lines

    PubMed Central

    Busschots, Steven; O’Toole, Sharon; O’Leary, John J.; Stordal, Britta

    2014-01-01

    Many protocols used for measuring the growth of adherent monolayer cells in vitro are invasive, destructive and do not allow for the continued, undisturbed growth of cells within flasks. Protocols often use indirect methods for measuring proliferation. Microscopy techniques can analyse cell proliferation in a non-invasive or non-destructive manner but often use expensive equipment and software algorithms. In this method images of cells within flasks are captured by photographing under a standard inverted phase contract light microscope using a digital camera with a camera lens adaptor. Images are analysed for confluence using ImageJ freeware resulting in a measure of confluence known as an Area Fraction (AF) output. An example of the AF method in use on OVCAR8 and UPN251 cell lines is included. • Measurements of confluence from growing adherent cell lines in cell culture flasks is obtained in a non-invasive, non-destructive, label-free manner. • The technique is quick, affordable and eliminates sample manipulation. • The technique provides an objective, consistent measure of when cells reach confluence and is highly correlated to manual counting with a haemocytometer. The average correlation co-efficient from a Spearman correlation (n = 3) was 0.99 ± 0.008 for OVCAR8 (p = 0.01) and 0.99 ± 0.01 for UPN251 (p = 0.01) cell lines. PMID:26150966

  5. Molecular imaging promotes progress in orthopedic research.

    PubMed

    Mayer-Kuckuk, Philipp; Boskey, Adele L

    2006-11-01

    Modern orthopedic research is directed towards the understanding of molecular mechanisms that determine development, maintenance and health of musculoskeletal tissues. In recent years, many genetic and proteomic discoveries have been made which necessitate investigation under physiological conditions in intact, living tissues. Molecular imaging can meet this demand and is, in fact, the only strategy currently available for noninvasive, quantitative, real-time biology studies in living subjects. In this review, techniques of molecular imaging are summarized, and applications to bone and joint biology are presented. The imaging modality most frequently used in the past was optical imaging, particularly bioluminescence and near-infrared fluorescence imaging. Alternate technologies including nuclear and magnetic resonance imaging were also employed. Orthopedic researchers have applied molecular imaging to murine models including transgenic mice to monitor gene expression, protein degradation, cell migration and cell death. Within the bone compartment, osteoblasts and their stem cells have been investigated, and the organic and mineral bone phases have been assessed. These studies addressed malignancy and injury as well as repair, including fracture healing and cell/gene therapy for skeletal defects. In the joints, molecular imaging has focused on the inflammatory and tissue destructive processes that cause arthritis. As described in this review, the feasibility of applying molecular imaging to numerous areas of orthopedic research has been demonstrated and will likely result in an increase in research dedicated to this powerful strategy. Molecular imaging holds great promise in the future for preclinical orthopedic research as well as next-generation clinical musculoskeletal diagnostics. PMID:16843078

  6. Molecular Imaging of Pancreatic Cancer with Antibodies

    PubMed Central

    2015-01-01

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

  7. Molecular-Genetic Imaging of Cancer

    PubMed Central

    Minn, Il; Menezes, Mitchell E.; Sarkar, Siddik; Yarlagadda, Keerthi; Das, Swadesh K.; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B.; Pomper, Martin G.

    2015-01-01

    Molecular-genetic imaging of cancer using nonviral delivery systems has great potential for clinical application as a safe, efficient, noninvasive tool for visualization of various cellular processes including detection of cancer, and its attendant metastases. In recent years, significant effort has been expended in overcoming technical hurdles to enable clinical adoption of molecular-genetic imaging. This chapter will provide an introduction to the components of molecular-genetic imaging and recent advances on each component leading to safe, efficient clinical applications for detecting cancer. Combination with therapy, namely, generating molecular-genetic theranostic constructs, will provide further impetus for clinical translation of this promising technology. PMID:25287688

  8. Anatomical and molecular imaging of skin cancer

    PubMed Central

    Hong, Hao; Sun, Jiangtao; Cai, Weibo

    2008-01-01

    Skin cancer is the most common form of cancer types. It is generally divided into two categories: melanoma (∼ 5%) and nonmelanoma (∼ 95%), which can be further categorized into basal cell carcinoma, squamous cell carcinoma, and some rare skin cancer types. Biopsy is still the gold standard for skin cancer evaluation in the clinic. Various anatomical imaging techniques have been used to evaluate different types of skin cancer lesions, including laser scanning confocal microscopy, optical coherence tomography, high-frequency ultrasound, terahertz pulsed imaging, magnetic resonance imaging, and some other recently developed techniques such as photoacoustic microscopy. However, anatomical imaging alone may not be sufficient in guiding skin cancer diagnosis and therapy. Over the last decade, various molecular imaging techniques (in particular single photon emission computed tomography and positron emission tomography) have been investigated for skin cancer imaging. The pathways or molecular targets that have been studied include glucose metabolism, integrin αvβ3, melanocortin-1 receptor, high molecular weight melanoma-associated antigen, and several other molecular markers. Preclinical molecular imaging is thriving all over the world, while clinical molecular imaging has not lived up to the expectations because of slow bench-to-bedside translation. It is likely that this situation will change in the near future and molecular imaging will truly play an important role in personalized medicine of melanoma patients. PMID:21437135

  9. Molecular magnetic resonance imaging in cancer.

    PubMed

    Haris, Mohammad; Yadav, Santosh K; Rizwan, Arshi; Singh, Anup; Wang, Ena; Hariharan, Hari; Reddy, Ravinder; Marincola, Francesco M

    2015-01-01

    The ability to identify key biomolecules and molecular changes associated with cancer malignancy and the capacity to monitor the therapeutic outcome against these targets is critically important for cancer treatment. Recent developments in molecular imaging based on magnetic resonance (MR) techniques have provided researchers and clinicians with new tools to improve most facets of cancer care. Molecular imaging is broadly described as imaging techniques used to detect molecular signature at the cellular and gene expression levels. This article reviews both established and emerging molecular MR techniques in oncology and discusses the potential of these techniques in improving the clinical cancer care. It also discusses how molecular MR, in conjunction with other structural and functional MR imaging techniques, paves the way for developing tailored treatment strategies to enhance cancer care. PMID:26394751

  10. Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation

    NASA Technical Reports Server (NTRS)

    Cohen, Richard J.

    1999-01-01

    It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.

  11. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

    PubMed Central

    Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

    2015-01-01

    Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

  12. Towards a smart non-invasive fluid loss measurement system.

    PubMed

    Suryadevara, N K; Mukhopadhyay, S C; Barrack, L

    2015-04-01

    In this article, a smart wireless sensing non-invasive system for estimating the amount of fluid loss, a person experiences while physical activity is presented. The system measures three external body parameters, Heart Rate, Galvanic Skin Response (GSR, or skin conductance), and Skin Temperature. These three parameters are entered into an empirically derived formula along with the user's body mass index, and estimation for the amount of fluid lost is determined. The core benefit of the developed system is the affluence usage in combining with smart home monitoring systems to care elderly people in ambient assisted living environments as well in automobiles to monitor the body parameters of a motorist. PMID:25686913

  13. Non-Invasive Optical Biosensor for Probing Cell Signaling

    PubMed Central

    Fang, Ye

    2007-01-01

    Cell signaling mediated through a cellular target is encoded by spatial and temporal dynamics of downstream signaling networks. The coupling of temporal dynamics with spatial gradients of signaling activities guides cellular responses upon stimulation. Monitoring the integration of cell signaling in real time, if realized, would provide a new dimension for understanding cell biology and physiology. Optical biosensors including resonant waveguide grating (RWG) biosensor manifest a physiologically relevant and integrated cellular response related to dynamic redistribution of cellular matters, thus providing a non-invasive means for cell signaling study. This paper reviews recent progresses in biosensor instrumentation, and theoretical considerations and potential applications of optical biosensors for whole cell sensing.

  14. Non-invasive techniques for determining musculoskeleton body composition

    SciTech Connect

    Cohn, S.H.

    1984-01-01

    In vivo neutron activation analysis, combined with gamma spectrometry, has ushered in a new era of clinical diagnosis and evaluation of therapies, as well as investigation into and modelling of body composition in both normal individuals and patients suffering from various diseases and dysfunctions. Body composition studies have provided baseline data on such vital constituents as nitrogen, potassium and calcium. The non-invasive measurement techniques are particularly suitable for study of the musculo-skeletal changes in body composition. Of particular relevance here is the measurement of calcium loss in astronauts during prolonged space flights.

  15. A simple highly efficient non invasive EMG-based HMI.

    PubMed

    Vitiello, N; Olcese, U; Oddo, C M; Carpaneto, J; Micera, S; Carrozza, M C; Dario, P

    2006-01-01

    Muscle activity recorded non-invasively is sufficient to control a mobile robot if it is used in combination with an algorithm for its asynchronous analysis. In this paper, we show that several subjects successfully can control the movements of a robot in a structured environment made up of six rooms by contracting two different muscles using a simple algorithm. After a small training period, subjects were able to control the robot with performances comparable to those achieved manually controlling the robot. PMID:17945773

  16. Neurophotonics: non-invasive optical techniques for monitoring brain functions.

    PubMed

    Torricelli, Alessandro; Contini, Davide; Dalla Mora, Alberto; Pifferi, Antonio; Re, Rebecca; Zucchelli, Lucia; Caffini, Matteo; Farina, Andrea; Spinelli, Lorenzo

    2014-01-01

    The aim of this review is to present the state of the art of neurophotonics, a recently founded discipline lying at the interface between optics and neuroscience. While neurophotonics also includes invasive techniques for animal studies, in this review we focus only on the non-invasive methods that use near infrared light to probe functional activity in the brain, namely the fast optical signal, diffuse correlation spectroscopy, and functional near infrared spectroscopy methods. We also present an overview of the physical principles of light propagation in biological tissues, and of the main physiological sources of signal. Finally, we discuss the open issues in models, instrumentation, data analysis and clinical approaches. PMID:25764252

  17. Non-invasive health status detection system using Gabor filters based on facial block texture features.

    PubMed

    Shu, Ting; Zhang, Bob

    2015-04-01

    Blood tests allow doctors to check for certain diseases and conditions. However, using a syringe to extract the blood can be deemed invasive, slightly painful, and its analysis time consuming. In this paper, we propose a new non-invasive system to detect the health status (Healthy or Diseased) of an individual based on facial block texture features extracted using the Gabor filter. Our system first uses a non-invasive capture device to collect facial images. Next, four facial blocks are located on these images to represent them. Afterwards, each facial block is convolved with a Gabor filter bank to calculate its texture value. Classification is finally performed using K-Nearest Neighbor and Support Vector Machines via a Library for Support Vector Machines (with four kernel functions). The system was tested on a dataset consisting of 100 Healthy and 100 Diseased (with 13 forms of illnesses) samples. Experimental results show that the proposed system can detect the health status with an accuracy of 93 %, a sensitivity of 94 %, a specificity of 92 %, using a combination of the Gabor filters and facial blocks. PMID:25722202

  18. Molecular imaging of oncolytic viral therapy

    PubMed Central

    Haddad, Dana; Fong, Yuman

    2015-01-01

    Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy. PMID:27119098

  19. Molecular imaging of oncolytic viral therapy.

    PubMed

    Haddad, Dana; Fong, Yuman

    2015-01-01

    Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy. PMID:27119098

  20. Activatable Molecular Probes for Cancer Imaging

    PubMed Central

    Lee, Seulki; Xie, Jin; Chen, Xiaoyuan

    2013-01-01

    The development of highly sensitive and specific molecular probes for cancer imaging still remains a daunting challenge. Recently, interdisciplinary research at the interface of imaging sciences and bionanoconjugation chemistry has generated novel activatable imaging probes that can provide high-resolution imaging with ultra-low background signals. Activatable imaging probes are designed to amplify output imaging signals in response to specific biomolecular recognition or environmental changes in real time. This review introduces and highlights the unique design strategies and applications of various activatable imaging probes in cancer imaging. PMID:20388112

  1. [Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis].

    PubMed

    Shin, Jung Woo; Park, Neung Hwa

    2016-07-25

    The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis. PMID:27443617

  2. Does function fit structure? A ground truth for non-invasive neuroimaging

    PubMed Central

    Stevenson, Claire; Brookes, Matthew; López, José David; Troebinger, Luzia; Mattout, Jeremie; Penny, William; Morris, Peter; Hillebrand, Arjan; Henson, Richard; Barnes, Gareth

    2014-01-01

    There are now a number of non-invasive methods to image human brain function in-vivo. However, the accuracy of these images remains unknown and can currently only be estimated through the use of invasive recordings to generate a functional ground truth. Neuronal activity follows grey matter structure and accurate estimates of neuronal activity will have stronger support from accurate generative models of anatomy. Here we introduce a general framework that, for the first time, enables the spatial distortion of a functional brain image to be estimated empirically. We use a spherical harmonic decomposition to modulate each cortical hemisphere from its original form towards progressively simpler structures, ending in an ellipsoid. Functional estimates that are not supported by the simpler cortical structures have less inherent spatial distortion. This method allows us to compare directly between magnetoencephalography (MEG) source reconstructions based upon different assumption sets without recourse to functional ground truth. PMID:24636880

  3. A New Quantitative Method for the Non-Invasive Documentation of Morphological Damage in Paintings Using RTI Surface Normals

    PubMed Central

    Manfredi, Marcello; Bearman, Greg; Williamson, Greg; Kronkright, Dale; Doehne, Eric; Jacobs, Megan; Marengo, Emilio

    2014-01-01

    In this paper we propose a reliable surface imaging method for the non-invasive detection of morphological changes in paintings. Usually, the evaluation and quantification of changes and defects results mostly from an optical and subjective assessment, through the comparison of the previous and subsequent state of conservation and by means of condition reports. Using quantitative Reflectance Transformation Imaging (RTI) we obtain detailed information on the geometry and morphology of the painting surface with a fast, precise and non-invasive method. Accurate and quantitative measurements of deterioration were acquired after the painting experienced artificial damage. Morphological changes were documented using normal vector images while the intensity map succeeded in highlighting, quantifying and describing the physical changes. We estimate that the technique can detect a morphological damage slightly smaller than 0.3 mm, which would be difficult to detect with the eye, considering the painting size. This non-invasive tool could be very useful, for example, to examine paintings and artwork before they travel on loan or during a restoration. The method lends itself to automated analysis of large images and datasets. Quantitative RTI thus eases the transition of extending human vision into the realm of measuring change over time. PMID:25010699

  4. Optical Molecular Imaging in the Gastrointestinal Tract

    PubMed Central

    Carns, Jennifer; Keahey, Pelham; Quang, Timothy; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

    2013-01-01

    Recent developments in optical molecular imaging allow for real-time identification of morphological and biochemical changes in tissue associated with gastrointestinal neoplasia. This review summarizes widefield and high resolution imaging modalities currently in pre-clinical and clinical evaluation for the detection of colorectal cancer and esophageal cancer. Widefield techniques discussed include high definition white light endoscopy, narrow band imaging, autofluoresence imaging, and chromoendoscopy; high resolution techniques discussed include probe-based confocal laser endomicroscopy, high-resolution microendoscopy, and optical coherence tomography. Finally, new approaches to enhance image contrast using vital dyes and molecular-specific targeted contrast agents are evaluated. PMID:23735112

  5. Non-invasive methodology for diagnostics of bearing impacts

    NASA Astrophysics Data System (ADS)

    Chi, John N.

    2007-04-01

    Various events in reciprocating machinery, such as connecting rod or piston movement, and diesel combustion produce a series of highly transient forces within the machine. These events generate force transients of short duration and broad frequency content. Even though these events may be part of a machine cycle and therefore periodic, it is often more appropriate to treat them on an individual basis because more diagnostics information is available from a single waveform during a cycle than from averages over several cycles. However, it is very rare for one to have direct access to source waveforms because of the expense and reliability problems associated with the required instrumentation, and non-invasive techniques will have to be used. This paper explores the use of cepstral smoothing and minimum phase extraction technique for non-invasive diagnostics of bearing impacts in reciprocating machinery. The methodology is based on extracting diagnostic signals from vibration measurements taken at a "convenient" location such as the crankshaft casing or bearing end-cap, and consists of source identification, diagnostic signature recovery, and diagnostic system decision-making. A dynamic simulation with lumped mass model is developed to analyze bearing impacts for the big end bearings, experimental measurements from accelerometers, transfer functions of vibration, and the structural response are presented.

  6. Influence of hemoglobin on non-invasive optical bilirubin sensing

    NASA Astrophysics Data System (ADS)

    Jiang, Jingying; Gong, Qiliang; Zou, Da; Xu, Kexin

    2012-03-01

    Since the abnormal metabolism of bilirubin could lead to diseases in the human body, especially the jaundice which is harmful to neonates. Traditional invasive measurements are difficult to be accepted by people because of pain and infection. Therefore, the real-time and non-invasive measurement of bilirubin is of great significance. However, the accuracy of currently transcutaneous bilirubinometry(TcB) is generally not high enough, and affected by many factors in the human skin, mostly by hemoglobin. In this talk, absorption spectra of hemoglobin and bilirubin have been collected and analyzed, then the Partial Least Squares (PLS) models have been built. By analyzing and comparing the Correlation and Root Mean Square Error of Prediction(RMSEP), the results show that the Correlation of bilirubin solution model is larger than that of the mixture solution added with hemoglobin, and its RMSEP value is smaller than that of mixture solution. Therefore, hemoglobin has influences on the non-invasive optical bilirubin sensing. In next step, it is necessary to investigate how to eliminate the influence.

  7. Examination of postmortem retinal folds: A non-invasive study.

    PubMed

    Oshima, Toru; Yoshikawa, Hiroshi; Ohtani, Maki; Mimasaka, Sohtaro

    2015-02-01

    The postmortem retinal fold has been previously documented, but its mechanism of formation is not known. All previous studies of the fold involved invasive techniques and the postmortem ocular fundus has yet to be non-invasively examined. Our study used the non-invasive techniques of monocular indirect ophthalmoscopy and ocular echography to examine 79 postmortem eyes of 42 bodies. We examined whether the postmortem retinal fold was associated with postmortem time, position, and/or age. Age was significantly associated with postmortem retinal fold formation (Mann-Whitney U test, P = 0.013), which led us to examine the effect of posterior vitreous detachment (PVD) on retinal folds. The absence of a PVD was statistically associated with the presence of a retinal fold (Fisher's exact test, P < 0.0001). Interestingly, the presence of a PVD was also significantly correlated with retinal fold height (Mann-Whitney U test, P < 0.0001). Therefore, we hypothesized that retinal folds result from postmortem vitreoretinal traction caused by eyeball flaccidity. We also believe that the loss of retinochoroidal hydrostatic pressure plays a role. It is important that forensic pathologists not confuse a postmortem retinal fold with traumatic retinal detachment or perimacular retinal folds caused by child abuse. When child abuse is suspected, forensic pathologists should perform enucleation and a subsequent histological examination for confirmation. PMID:25623189

  8. Modulation of Untruthful Responses with Non-Invasive Brain Stimulation

    PubMed Central

    Fecteau, Shirley; Boggio, Paulo; Fregni, Felipe; Pascual-Leone, Alvaro

    2013-01-01

    Deceptive abilities have long been studied in relation to personality traits. More recently, studies explored the neural substrates associated with deceptive skills suggesting a critical role of the prefrontal cortex. Here we investigated whether non-invasive brain stimulation over the dorsolateral prefrontal cortex (DLPFC) could modulate generation of untruthful responses about subject’s personal life across contexts (i.e., deceiving on guilt-free questions on daily activities; generating previously memorized lies about past experience; and producing spontaneous lies about past experience), as well as across modality responses (verbal and motor responses). Results reveal that real, but not sham, transcranial direct current stimulation (tDCS) over the DLPFC can reduce response latency for untruthful over truthful answers across contexts and modality responses. Also, contexts of lies seem to incur a different hemispheric laterality. These findings add up to previous studies demonstrating that it is possible to modulate some processes involved in generation of untruthful answers by applying non-invasive brain stimulation over the DLPFC and extend these findings by showing a differential hemispheric contribution of DLPFCs according to contexts. PMID:23550273

  9. Non-invasive screening of cytochrome c oxidase deficiency in children using a dipstick immunocapture assay.

    PubMed

    Rodinová, M; Trefilová, E; Honzík, T; Tesařová, M; Zeman, J; Hansíková, H

    2014-01-01

    Cytochrome c oxidase (CIV) deficiency is among the most common childhood mitochondrial disorders. The diagnosis of this deficiency is complex, and muscle biopsy is used as the gold standard of diagnosis. Our aim was to minimize the patient burden and to test the use of a dipstick immunocapture assay (DIA) to determine the amount of CIV in non-invasively obtained buccal epithelial cells. Buccal smears were obtained from five children with Leigh syndrome including three children exhibiting a previously confirmed CIV deficiency in muscle and fibroblasts and two children who were clinical suspects for CIV deficiency; the smear samples were analysed using CI and CIV human protein quantity dipstick assay kits. Samples from five children of similar age and five adults were used as controls. Analysis of the controls demonstrated that only samples of buccal cells that were frozen for a maximum of 4 h after collection provide accurate results. All three patients with confirmed CIV deficiency due to mutations in the SURF1 gene exhibited significantly lower amounts of CIV than the similarly aged controls; significantly lower amounts were also observed in two new patients, for whom later molecular analysis also confirmed pathologic mutations in the SURF1 gene. We conclude that DIA is a simple, fast and sensitive method for the determination of CIV in buccal cells and is suitable for the screening of CIV deficiency in non-invasively obtained material from children who are suspected of having mitochondrial disease. PMID:25629267

  10. The quest for non-invasive delivery of bioactive macromolecules: A focus on heparins

    PubMed Central

    Motlekar, Nusrat A.; Youan, Bi-Botti C.

    2006-01-01

    The development of a non-invasive drug delivery system for unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) has been the elusive goal of several research groups since the initial discovery of this glycosaminogylcan by McLean in 1916. After a brief update on current parenteral formulations of UFH and LMWHs, this review revisits past and current strategies intended to identify alternative routes of administration (e.g. oral, sublingual, rectal, nasal, pulmonary and transdermal). The following strategies have been used to improve the bioavailability of this bioactive macromolecule by various routes: (i) enhancement in cell-membrane permeabilization, (ii) modification of the tight-junctions, (iii) increase in lipophilicity and (iv) protection against acidic pH of the stomach. Regardless of the route of administration, a simplified unifying principle for successful non-invasive macromolecular drug delivery may be: “to reversibly overcome the biological, biophysical and biochemical barriers and to safely and efficiently improve the in vivo spatial and temporal control of the drug in order to achieve a clinically acceptable therapeutic advantage”. Future macromolecular drug delivery research should embrace a more systemic approach taking into account recent advances in genomics/proteomics and nanotechnology. PMID:16777255

  11. Historical and non-invasive samples: a study case of genotyping errors in newly isolated microsatellites for the lesser anteater (Tamandua tetradactyla L., Pilosa).

    PubMed

    Clozato, Camila L; Moraes-Barros, Nadia; Santos, Fabrício R; Morgante, João S

    2014-05-01

    Tamandua tetradactyla (Pilosa), the lesser anteater, is a medium-size mammal from South America. Its wide distribution through different landscapes, solitary and nocturnal habits, and the difficulty to capture and contain specimens limit the amount of individuals and populations sampled during fieldworks. These features along with the lack of specific molecular markers for the lesser anteater might be the causes for paucity in population genetic studies for the species. Historical samples from museum specimens, such as skins, and non-invasive samples, such as plucked hair, can be supplementary sources of DNA samples. However, the DNA quantity and quality of these samples may be limiting factors in molecular studies. In this study, we describe nine microsatellite loci for T. tetradactyla and test the amplification success, data reliability and estimate errors on both historical and non-invasive sample sets. We tested nine polymorphic microsatellites and applied the quality index approach to evaluate the relative performance in genotype analysis of 138 historical samples (study skin) and 19 non-invasive samples (plucked hair). The observed results show a much superior DNA quality of non-invasive over historical samples and support the quality index analysis as a practical tool to exclude samples with doubtful performance in genetic studies. We also found a relationship between the age of non-invasive samples and DNA quality, but lack of evidence of this pattern for historical samples. PMID:24345284

  12. Non-invasive Investigations of Paintings by Portable Instrumentation: The MOLAB Experience.

    PubMed

    Brunetti, B; Miliani, C; Rosi, F; Doherty, B; Monico, L; Romani, A; Sgamellotti, A

    2016-02-01

    The in situ non invasive methods have experienced a significant development in the last decade because they meet specific needs of analytical chemistry in the field of cultural heritage where  artworks are rarely moved from their locations, sampling is rarely permitted, and analytes are a wide range of inorganic, organic and organometallic substances in complex and precious matrices. MOLAB, a unique collection of integrated mobile instruments, has greatly contributed to demonstrate that it is now possible to obtain satisfactory results in the study of a variety of heritage objects without sampling or moving them to a laboratory. The current chapter describes an account of these results with particular attention to ancient, modern, and contemporary paintings. Several non-invasive methods by portable equipment, including XRF, mid- and near-FTIR, UV-Vis and Raman spectroscopy, as well as XRD, are discussed in detail along with their impact on our understanding of painting materials and execution techniques. Examples of successful applications are given, both for point analyses and hyperspectral imaging approaches. Lines for future perspectives are finally drawn. PMID:27572993

  13. Non-invasive quantification of skin injury resulting from exposure to sulphur mustard and Lewisite vapours.

    PubMed

    Chilcott, R P; Brown, R F; Rice, P

    2000-05-01

    The severity and progression of skin lesions resulting from exposure to the chemical warfare agents Lewisite (L) and sulphur mustard (SM) have been investigated using the non-invasive biophysical methods of evaporimetry and reflectance spectroscopy in large white pigs in vivo. Erythema (redness) expressed immediately after exposure to L or SM vapours appeared to be related to the lesion severity as demonstrated by histopathological analysis. Skin brightness correlated well with scab formation whereas blueness (cyanosis) did not appreciably alter throughout the study. Rates of transepidermal water loss (TEWL) changed both with occlusion (during vapour exposure) and also mirrored the progression of macroscopic skin injury after 12 h. Whilst no single parameter could be used in isolation to ascertain the severity and subsequent progression of the skin lesions, measurement of erythema, skin brightness and TEWL could provide quantitative, non-invasive methods for determining the efficacy of antidotes or therapies to prevent the toxic effects of chemical warfare agents. However, neither colourimetry or TEWL provided a clinical evaluation of such lesions that were comparable with the prognostic capabilities of laser Doppler imaging. PMID:10741590

  14. Acute changes in liver tumour perfusion measured non-invasively with arterial spin labelling

    PubMed Central

    Johnson, S Peter; Ramasawmy, Rajiv; Campbell-Washburn, Adrienne E; Wells, Jack A; Robson, Mathew; Rajkumar, Vineeth; Lythgoe, Mark F; Pedley, R Barbara; Walker-Samuel, Simon

    2016-01-01

    Background: Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503. Methods: SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R2* MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg−1 OXi4503. Results: A significant decrease in SW1222 tumour perfusion was observed (−43±33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R2* in LS174T tumours (28±25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits. Conclusions: Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting. PMID:27031853

  15. Non-invasive characterization of intracranial tumors by magnetic resonance elastography

    NASA Astrophysics Data System (ADS)

    Simon, M.; Guo, J.; Papazoglou, S.; Scholand-Engler, H.; Erdmann, C.; Melchert, U.; Bonsanto, M.; Braun, J.; Petersen, D.; Sack, I.; Wuerfel, J.

    2013-08-01

    Presurgical, non-invasive methods of differentiating brain tumors have remained unsatisfactory even for specialized academic hospitals. Despite major advances in clinical and neuroradiological diagnostic techniques, the majority of neurooncology patients still need to undergo a brain biopsy for diagnosis. Recent single cell experiments suggested that biomechanical cell properties might be very sensitive in detecting cellular malignancy. Accordingly, we investigated magnetic resonance elastography (MRE) as an investigative tool for the clinical routine diagnostic work-up of intracranial neoplasm. In order to obtain sufficient spatial resolution for the biomechanical characterization of intracranial tumors, we modified a recently introduced least-squares solution of the stationary wave equation, facilitating stable solutions of the magnitude |G*| and the phase angle φ of the complex shear modulus G*. MRE was added to a routine diagnostic or presurgical neuroradiological magnetic resonance imaging work-up in 16 prospective patients and it was well tolerated in all cases. Our preliminary tumor MRE data revealed alterations in viscoelastic constants, e.g. a loss of stiffness in malignancies compared to healthy reference tissue, or benign variants. Based on larger studies on selected tumor entities to establish threshold and reference values for future diagnostic purposes, MRE may thus provide a predictive marker for tumor malignancy and thereby contribute to an early non-invasive clinical assessment of suspicious cerebral lesions.

  16. Development of non-invasive method for assessment of hepatic steatosis.

    PubMed

    Morikawa, H; Mano, K; Horinaka, H; Matsunaka, T; Matsumoto, Y; Ida, T; Kawaguchi, Y; Wada, K; Kawada, N

    2016-12-01

    Steatosis is a critical feature of liver disease and is considered to play a pivotal role in the progression of nonalcoholic fatty liver disease, as well as being a surrogate marker of metabolic syndrome. The purpose of this study was to develop a non-invasive diagnostic method for assessment of liver steatosis. It is well known that ultrasonic velocity depends on materials and temperature. For example, the ultrasonic velocity in water is 1530m/s at 37°C and 1534m/s at 39°C, while that in fat is 1412m/s at 37°C and 1402m/s at 39°C. On this basis, we thought that the percentage of fat in hepatic steatosis could be assessed by detecting changes of ultrasonic in the liver, caused by warming. In order to confirm the effectiveness of this method, we obtained the ultrasonic velocity changes of tissue phantom including lard oil and the liver of living rabbit by ultrasonic warming, and then succeeded in 2-D imaging of ultrasonic velocity changes of the phantom and the liver of living rabbit. We named this the ultrasonic velocity-change method. The experimental results show the possibility that hepatic steatosis could be characterized using our novel, non-invasive method. PMID:27567038

  17. Congenital coronary artery anomalies silent until geriatric age: non-invasive assessment, angiography tips, and treatment

    PubMed Central

    Rigatelli, Gianluca; Dell'Avvocata, Fabio; Van Tan, Nguyen; Daggubati, Rames; Nanijundappa, Aravinda

    2015-01-01

    Coronary artery anomalies (CAAs) may be discovered more often as incidental findings during the normal diagnostic process for other cardiac diseases or less frequently on the basis of manifestations of myocardial ischemia. The cardiovascular professional may be involved in their angiographic diagnosis, functional assessment and eventual endovascular treatment. A complete angiographic definition is mandatory in order to understand the functional effects and plan any intervention in CAAs: computed tomography and magnetic resonance imaging are useful non-invasive tools to detect three-dimensional morphology of the anomalies and its relationships with contiguous cardiac structures, whereas coronary arteriography remains the gold standard for a definitive anatomic picture. A practical idea of the possible functional significance is mandatory for deciding how to manage CAAs: non-invasive stress tests and in particular the invasive pharmacological stress tests with or without intravascular ultrasound monitoring can assess correctly the functional significance of the most CAAs. Finally, the knowledge of the particular endovascular techniques and material is of paramount importance for achieving technical and clinical success. CAAs represent a complex issue, which rarely involve the cardiovascular professional at different levels. A timely practical knowledge of the main issues regarding CAAs is important in the management of such entities. PMID:25678906

  18. Non-invasive volumetric assessment of aortic atheroma: a core laboratory validation using computed tomography angiography.

    PubMed

    Hammadah, Muhammad; Qintar, Mohammed; Nissen, Steven E; John, Julie St; Alkharabsheh, Saqer; Mobolaji-Lawal, Motunrayo; Philip, Femi; Uno, Kiyoko; Kataoka, Yu; Babb, Brett; Poliszczuk, Roman; Kapadia, Samir R; Tuzcu, E Murat; Schoenhagen, Paul; Nicholls, Stephen J; Puri, Rishi

    2016-01-01

    Aortic atherosclerosis has been linked with worse peri- and post-procedural outcomes following a range of aortic procedures. Yet, there are currently no standardized methods for non-invasive volumetric pan-aortic plaque assessment. We propose a novel means of more accurately assessing plaque volume across whole aortic segments using computed tomography angiography (CTA) imaging. Sixty patients who underwent CTA prior to trans-catheter aortic valve implantation were included in this analysis. Specialized software analysis (3mensio Vascular™, Pie Medical, Maastricht, Netherlands) was used to reconstruct images using a centerline approach, thus creating true cross-sectional aortic images, akin to those images produced with intravascular ultrasonography. Following aortic segmentation (from the aortic valve to the renal artery origin), atheroma areas were measured across multiple contiguous evenly spaced (10 mm) cross-sections. Percent atheroma volume (PAV), total atheroma volume (TAV) and calcium score were calculated. In our populations (age 79.9 ± 8.5 years, male 52 %, diabetes 27 %, CAD 84 %, PVD 20 %), mean ± SD number of cross sections measured for each patient was 35.1 ± 3.5 sections. Mean aortic PAV and TAV were 33.2 ± 2.51 % and 83,509 ± 17,078 mm(3), respectively. Median (IQR) calcium score was 1.5 (0.7-2.5). Mean (SD) inter-observer coefficient of variation and agreement for plaque area among 4 different analysts was 14.1 (5.4), and the mean (95 % CI) Lin's concordance correlation coefficient was 0.79 (0.62-0.89), effectively simulating a Core Laboratory scenario. We provide an initial validation of cross-sectional volumetric aortic atheroma assessment using CTA. This proposed methodology highlights the potential for utilizing non-invasive aortic plaque imaging for risk prediction across a range of clinical scenarios. PMID:25962864

  19. Molecular Imaging of Healing After Myocardial Infarction

    PubMed Central

    Naresh, Nivedita K; Ben-Mordechai, Tamar; Leor, Jonathan

    2011-01-01

    The progression from acute myocardial infarction (MI) to heart failure continues to be a major cause of morbidity and mortality. Potential new therapies for improved infarct healing such as stem cells, gene therapy, and tissue engineering are being investigated. Noninvasive imaging plays a central role in the evaluation of MI and infarct healing, both clinically and in preclinical research. Traditionally, imaging has been used to assess cardiac structure, function, perfusion, and viability. However, new imaging methods can be used to assess biological processes at the cellular and molecular level. We review molecular imaging techniques for evaluating the biology of infarct healing and repair. Specifically, we cover recent advances in imaging the various phases of MI and infarct healing such as apoptosis, inflammation, angiogenesis, extracellular matrix deposition, and scar formation. Significant progress has been made in preclinical molecular imaging, and future challenges include translation of these methods to clinical practice. PMID:21869911

  20. TU-F-12A-01: Quantitative Non-Linear Compartment Modeling of 89Zr- and 124I- Labeled J591 Monoclonal Antibody Kinetics Using Serial Non-Invasive Positron Emission Tomography Imaging in a Pre-Clinical Human Prostate Cancer Mouse Model

    SciTech Connect

    Fung, EK; Cheal, SM; Chalasani, S; Fareedy, SB; Punzalan, B; Humm, JL; Osborne, JR; Larson, SM; Zanzonico, PB; Otto, B; Bander, NH

    2014-06-15

    Purpose: To examine the binding kinetics of human IgG monoclonal antibody J591 which targets prostate-specific membrane antigen (PSMA) in a pre-clinical mouse cancer model using quantitative PET compartmental analysis of two radiolabeled variants. Methods: PSMA is expressed in normal human prostate, and becomes highly upregulated in prostate cancer, making it a promising therapeutic target. Two forms of J591, radiolabeled with either {sup 89}Zr or {sup 124}I, were prepared. {sup 89}Zr is a radiometal that becomes trapped in the cell upon internalization by the antigen-antibody complex, while radioiodine leaves the cell. Mice with prostate cancer xenografts underwent non-invasive serial imaging on a Focus 120 microPET up to 144 hours post-injection of J591. A non-linear compartmental model describing the binding and internalization of antibody in tumor xenograft was developed and applied to the PET-derived time-activity curves. The antibody-antigen association rate constant (ka), total amount of antigen per gram tumor (Ag-total), internalization rate of antibody-antigen complex, and efflux rate of radioisotope from tumor were fitted using the model. The surface-bound and the internalized activity were also estimated. Results: Values for ka, Ag-total, and internalization rate were found to be similar regardless of radiolabel payload used. The efflux rate, however, was ∼ 9-fold higher for {sup 124}I-J591 than for {sup 89}Zr-J591. Time-dependent surface-bound and internalized radiotracer activity were similar for both radiolabels at early times post-injection, but clearly differed beyond 24 hours. Conclusion: Binding and internalization of J591 to PSMA-expressing tumor xenografts were similar when radiolabeled with either {sup 89}Zr or {sup 124}I payload. The difference in efflux of radioactivity from tumor may be attributable to differential biological fate intracellularly of the radioisotopes. This has great significance for radioimmunotherapy and antibody

  1. The importance of optical methods for non-invasive measurements in the skin care industry

    NASA Astrophysics Data System (ADS)

    Stamatas, Georgios N.

    2010-02-01

    Pharmaceutical and cosmetic industries are concerned with treating skin disease, as well as maintaining and promoting skin health. They are dealing with a unique tissue that defines our body in space. As such, skin provides not only the natural boundary with the environment inhibiting body dehydration as well as penetration of exogenous aggressors to the body, it is also ideally situated for optical measurements. A plurality of spectroscopic and imaging methods is being used to understand skin physiology and pathology and document the effects of topically applied products on the skin. The obvious advantage of such methods over traditional biopsy techniques is the ability to measure the cutaneous tissue in vivo and non-invasively. In this work, we will review such applications of various spectroscopy and imaging methods in skin research that is of interest the cosmetic and pharmaceutical industry. Examples will be given on the importance of optical techniques in acquiring new insights about acne pathogenesis and infant skin development.

  2. Non-Invasive Investigation of Bone Adaptation in Humans to Cumulative Daily Mechanical Loading

    NASA Technical Reports Server (NTRS)

    Whalen, Robert; Cleek, Tammy; Sode, Miki

    2003-01-01

    The goal of our research is to better understand the functional relationship between cumulative daily skeletal loading generated by daily activity and the regulation of bone density and bone structure. We have proposed the calcaneus and tibia as useful model bone sites loaded by internal forces in equilibrium with the ground reaction force during gait. The daily history of the ground reaction force is a good relative measure of daily lower limb and calcaneal loading that can be compared to bone density and structure of the calcaneus and cross-sectional geometry of the tibia and fibula. Over the past several years, we have developed image-processing technologies to improve our ability to measure bone density and structure in the calcaneus and lower leg non-invasively with computed tomography and bone densitometry, or DXA. The objective of our current research effort is to determine the accuracy and precision of our CT and DXA image processing methods.

  3. A holistic multimodal approach to the non-invasive analysis of watercolour paintings

    NASA Astrophysics Data System (ADS)

    Kogou, Sotiria; Lucian, Andrei; Bellesia, Sonia; Burgio, Lucia; Bailey, Kate; Brooks, Charlotte; Liang, Haida

    2015-11-01

    A holistic approach using non-invasive multimodal imaging and spectroscopic techniques to study the materials (pigments, drawing materials and paper) and painting techniques of watercolour paintings is presented. The non-invasive imaging and spectroscopic techniques include VIS-NIR reflectance spectroscopy and multispectral imaging, micro-Raman spectroscopy, X-ray fluorescence spectroscopy (XRF) and optical coherence tomography (OCT). The three spectroscopic techniques complement each other in pigment identification. Multispectral imaging (near-infrared bands), OCT and micro-Raman complement each other in the visualisation and identification of the drawing material. OCT probes the micro-structure and light scattering properties of the substrate, while XRF detects the elemental composition that indicates the sizing methods and the filler content. The multiple techniques were applied in a study of forty-six nineteenth-century Chinese export watercolours from the Victoria and Albert Museum (V&A) and the Royal Horticultural Society (RHS) to examine to what extent the non-invasive analysis techniques employed complement each other and how much useful information about the paintings can be extracted to address art conservation and history questions. A micro-destructive technique of micro-fade spectrometry was used to assess the vulnerability of the paintings to light exposure. Most of the paint and paper substrates were found to be more stable than ISO Blue Wool 3. The palette was found to be composed of mostly traditional Chinese pigments. While the synthetic pigment, Prussian blue, made in Europe, was found on some of the paintings, none was found on the RHS paintings accurately recorded as being between 1817 and 1831 even though it is known that Prussian blue was imported to China during this period. The scale insect dyes, lac and cochineal, were detected on nearly every painting including those that fall within the identified date range. Cochineal is known to have

  4. Molecular Imaging of Proteases in Cancer

    PubMed Central

    Yang, Yunan; Hong, Hao; Zhang, Yin; Cai, Weibo

    2010-01-01

    Proteases play important roles during tumor angiogenesis, invasion, and metastasis. Various molecular imaging techniques have been employed for protease imaging: optical (both fluorescence and bioluminescence), magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). In this review, we will summarize the current status of imaging proteases in cancer with these techniques. Optical imaging of proteases, in particular with fluorescence, is the most intensively validated and many of the imaging probes are already commercially available. It is generally agreed that the use of activatable probes is the most accurate and appropriate means for measuring protease activity. Molecular imaging of proteases with other techniques (i.e. MRI, SPECT, and PET) has not been well-documented in the literature which certainly deserves much future effort. Optical imaging and molecular MRI of protease activity has very limited potential for clinical investigation. PET/SPECT imaging is suitable for clinical investigation; however the optimal probes for PET/SPECT imaging of proteases in cancer have yet to be developed. Successful development of protease imaging probes with optimal in vivo stability, tumor targeting efficacy, and desirable pharmacokinetics for clinical translation will eventually improve cancer patient management. Not limited to cancer, these protease-targeted imaging probes will also have broad applications in other diseases such as arthritis, atherosclerosis, and myocardial infarction. PMID:20234801

  5. Molecular imaging of movement disorders

    PubMed Central

    Lizarraga, Karlo J; Gorgulho, Alessandra; Chen, Wei; De Salles, Antonio A

    2016-01-01

    caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders. PMID:27029029

  6. Molecular imaging of movement disorders.

    PubMed

    Lizarraga, Karlo J; Gorgulho, Alessandra; Chen, Wei; De Salles, Antonio A

    2016-03-28

    -to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders. PMID:27029029

  7. Molecular Imaging in Optical Coherence Tomography

    PubMed Central

    Mattison, Scott P.; Kim, Wihan; Park, Jesung; Applegate, Brian E.

    2015-01-01

    Optical coherence tomography (OCT) is a medical imaging technique that provides tomographic images at micron scales in three dimensions and high speeds. The addition of molecular contrast to the available morphological image holds great promise for extending OCT’s impact in clinical practice and beyond. Fundamental limitations prevent OCT from directly taking advantage of powerful molecular processes such as fluorescence emission and incoherent Raman scattering. A wide range of approaches is being researched to provide molecular contrast to OCT. Here we review those approaches with particular attention to those that derive their molecular contrast directly from modulation of the OCT signal. We also provide a brief overview of the multimodal approaches to gaining molecular contrast coincident with OCT. PMID:25821718

  8. Optical imaging: Ultrafast buffering by molecular gas

    NASA Astrophysics Data System (ADS)

    Hertz, Edouard; Lavorel, Bruno; Faucher, Olivier

    2011-02-01

    A simple molecular gas sample can be used to achieve ultrafast optical buffering in two-dimensional optical imaging, thus serving as a promising extension of the well-developed liquid-crystal display technology.

  9. Non-Invasive Detection of Anaemia Using Digital Photographs of the Conjunctiva

    PubMed Central

    Collings, Shaun; Thompson, Oliver; Hirst, Evan; Goossens, Louise; George, Anup; Weinkove, Robert

    2016-01-01

    Background and Aims Anaemia is a major health burden worldwide. Although the finding of conjunctival pallor on clinical examination is associated with anaemia, inter-observer variability is high, and definitive diagnosis of anaemia requires a blood sample. We aimed to detect anaemia by quantifying conjunctival pallor using digital photographs taken with a consumer camera and a popular smartphone. Our goal was to develop a non-invasive screening test for anaemia. Patients and Methods The conjunctivae of haemato-oncology in- and outpatients were photographed in ambient lighting using a digital camera (Panasonic DMC-LX5), and the internal rear-facing camera of a smartphone (Apple iPhone 5S) alongside an in-frame calibration card. Following image calibration, conjunctival erythema index (EI) was calculated and correlated with laboratory-measured haemoglobin concentration. Three clinicians independently evaluated each image for conjunctival pallor. Results Conjunctival EI was reproducible between images (average coefficient of variation 2.96%). EI of the palpebral conjunctiva correlated more strongly with haemoglobin concentration than that of the forniceal conjunctiva. Using the compact camera, palpebral conjunctival EI had a sensitivity of 93% and 57% and specificity of 78% and 83% for detection of anaemia (haemoglobin < 110 g/L) in training and internal validation sets, respectively. Similar results were found using the iPhone camera, though the EI cut-off value differed. Conjunctival EI analysis compared favourably with clinician assessment, with a higher positive likelihood ratio for prediction of anaemia. Conclusions Erythema index of the palpebral conjunctiva calculated from images taken with a compact camera or mobile phone correlates with haemoglobin and compares favourably to clinician assessment for prediction of anaemia. If confirmed in further series, this technique may be useful for the non-invasive screening for anaemia. PMID:27070544

  10. Neurophotonics: non-invasive optical techniques for monitoring brain functions

    PubMed Central

    Torricelli, Alessandro; Contini, Davide; Mora, Alberto Dalla; Pifferi, Antonio; Re, Rebecca; Zucchelli, Lucia; Caffini, Matteo; Farina, Andrea; Spinelli, Lorenzo

    2014-01-01

    Summary The aim of this review is to present the state of the art of neurophotonics, a recently founded discipline lying at the interface between optics and neuroscience. While neurophotonics also includes invasive techniques for animal studies, in this review we focus only on the non-invasive methods that use near infrared light to probe functional activity in the brain, namely the fast optical signal, diffuse correlation spectroscopy, and functional near infrared spectroscopy methods. We also present an overview of the physical principles of light propagation in biological tissues, and of the main physiological sources of signal. Finally, we discuss the open issues in models, instrumentation, data analysis and clinical approaches. PMID:25764252

  11. [Non-invasive brain stimulation for Parkinson's disease].

    PubMed

    Gajo, Gianandrea; Pollak, Pierre; Lüscher, Christian; Benninger, David

    2015-04-29

    Parkinson's disease (PD) is a major socio-economic burden increasing with the aging population. In advanced PD, the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation (NIBS) as an alternative therapeutic tool. NIBS could offer an alternative approach for patients at risk who are excluded from surgery and/or to treat refractory symptoms. The treatment of the freezing of gait, a major cause of disability and falls in PD patients, could be enhanced by transcranial direct current stimulation (tDCS). A therapeutic study is currently performed at the Department of Neurology at the CHUV. PMID:26062225

  12. [Elemental research on intelligent non-invasive temporary pacemakers].

    PubMed

    Nie, Bang-ji; Xu, Long; Xin, Xue-gang; Wang, Cheng-lai; Wu, Min-shan

    2005-01-01

    Some research on intelligent non-invasive temporary pacemakers is introduced in this paper. An industrial computer, some IC chips and other elements are used to construct its hardware, and its software is in C++ language. The experimental device has some intelligent functions of recognizing some arrhythmia. The system has a pacemaker module and an ECG monitor module. Its software includes a main program, a RS-232C communication program, a printer VxD, a pacing control VxD and ECG signal pretreatment and recognizing program and so on. The pacing-generating circuit is employed to make the precision control of pacing current. The communication between industrial-computer system and ECG module is completed through the DLL. The real time processing of ECG signals is based on filter method for a higher recognizing ratio. The system calculates several parameters to recognize certain arrhythmia and uses MIT/BIH database to validate the reliability of ECG recognition. PMID:15875682

  13. [Non-invasive prenatal testing: challenges for future implementation].

    PubMed

    Henneman, Lidewij; Page-Chrisiaens, G C M L Lieve; Oepkes, Dick

    2015-01-01

    The non-invasive prenatal test (NIPT) is an accurate and safe test in which blood from the pregnant woman is used to investigate if the unborn child possibly has trisomy 21 (Down's syndrome), trisomy 18 (Edwards' syndrome) or trisomy 13 (Patau syndrome). Since April 2014 the NIPT has been available in the Netherlands as part of the TRIDENT implementation project for those in whom the first trimester combined test showed an elevated risk (> 1:200) of trisomy, or on medical indication, as an alternative to chorionic villous sampling or amniocentesis. Since the introduction of the NIPT the use of these invasive tests, which are associated with a risk of miscarriage, has fallen steeply. The NIPT may replace the combined test. Also the number of conditions that is tested for can be increased. Modification of current prenatal screening will require extensive discussion, but whatever the modification, careful counseling remains essential to facilitate pregnant women's autonomous reproductive decision making. PMID:26530119

  14. Non-invasive Respiratory Support and Severe Retinopathy of Prematurity.

    PubMed

    Raghu, Rahul; Fisher, Marilyn; Cerone, Jennifer; Barry, Gerard

    2016-01-01

    The authors describe two premature infants who developed stage 3, zone I retinopathy of prematurity (ROP) with plus disease in both eyes, despite limited exposure to supra-ambient oxygen. Both infants received noninvasive respiratory support for several weeks. Both cases are notable because the ROP was more posterior and aggressive than is typical for the gestational ages or birth weights. These cases are insufficient to make definitive conclusions regarding the factors that cause ROP. Further investigation is required to determine if there is an association between the use of non-invasive respiratory support, even in the absence of supra-ambient oxygen, and severe ROP development. [J Pediatr Ophthalmol Strabismus. 2016;53:e47-e50.]. PMID:27537495

  15. Eyeblink conditioning: a non-invasive biomarker for neurodevelopmental disorders.

    PubMed

    Reeb-Sutherland, Bethany C; Fox, Nathan A

    2015-02-01

    Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition, abnormalities in the cerebellum, a region of the brain highly involved in EBC, have been implicated in a number of neurodevelopmental disorders including autism spectrum disorders (ASDs). In the current paper, we review studies that have employed EBC as a biomarker for several neurodevelopmental disorders including fetal alcohol syndrome, Down syndrome, fragile X syndrome, attention deficit/hyperactivity disorder, dyslexia, specific language impairment, and schizophrenia. In addition, we discuss the benefits of using such a tool in individuals with ASD. PMID:23942847

  16. Non-invasive ventilation in exacerbations of COPD

    PubMed Central

    Ambrosino, Nicolino; Vagheggini, Guido

    2007-01-01

    Randomized controlled trials have confirmed the evidence and helped to define when and where non invasive mechanical ventilation (NIV) should be the first line treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Noninvasive ventilation has its best indication in moderate-to-severe respiratory acidosis in patients with AECOPD. For this indication, studies conducted in ICU, in wards and in accident and emergency departments confirmed its effectiveness in preventing endotracheal intubation and reducing mortality. The skill of the health care team promotes proper NIV utilization and improves the patient outcome. Patients with severe acidosis or with altered levels of consciousness due to hypercapnic acute respiratory failure are exposed to high risk of NIV failure. In these patients a NIV trial may be attempted in closely monitored clinical settings where prompt endotracheal intubation may be assured. PMID:18268921

  17. Non-invasive Loading Model of Murine Osteoarthritis.

    PubMed

    Poulet, Blandine

    2016-07-01

    Osteoarthritis is the commonest degenerative joint disease, leading to joint pain and disability. The mouse has been the primary animal used for research, due to its size, relatively short lifespan, and the availability of genetically modified animals. Importantly, they show pathogenesis similar to osteoarthritis in humans. Mechanical loading is a major risk factor for osteoarthritis, and various mouse models have been developed to study the role and effects of mechanics on health and disease in various joints. This review describes the main mouse models used to non-invasively apply mechanical loads on joints. Most of the mouse models of osteoarthritis target the knee, including repetitive loading and joint injury such as ligament rupture, but a few studies have also characterised models for elbow, temporomandibular joint, and whole-body vibration spinal loading. These models are a great opportunity to dissect the influences of various types of mechanical input on joint health and disease. PMID:27177901

  18. Non-invasive assessment of skeletal muscle activity

    NASA Astrophysics Data System (ADS)

    Merletti, Roberto; Orizio, Claudio; di Prampero, Pietro E.; Tesch, Per

    2005-10-01

    After the first 3 years (2002-2005), the MAP project has made available: - systems fo electrodes, signal conditioning and digital processing for multichannel simultaneously-detected EMG and MMG as well as for simultaneous electrical stimulation and EMG detection with artifact cancellation. - innovative non-invasive techniques for the extraction of individual motor unit action potentials (MUAPS) and individual motor and MMG contributions from the surface EMG interference signal and the MMG signal. - processing techniques for extractions of indicators of progressive fatigue from the electrically-elicited (M-wave) EMG signal. - techniques for the analysis of dynamic multichannel EMG during cyclic or explosive exercise (in collaboration with project EXER/MAP-MED-027).

  19. Continuous non-invasive finger blood pressure monitoring in children.

    PubMed

    Tanaka, H; Thulesius, O; Yamaguchi, H; Mino, M; Konishi, K

    1994-06-01

    We evaluated the performance of continuous non-invasive finger arterial pressure measurement using the volume-clamp technique (Finapres). This study was designed to compare finger arterial pressure with brachial blood pressure estimated by the auscultatory method in 217 children (90 boys and 127 girls) aged 4-16 years and in 38 adults (aged 18-45 years). Finger and brachial artery pressure readings were obtained consecutively from the ipsilateral side in the supine position. Finger arterial pressure waveforms were recorded in all children except 4 with small and thin fingers. There was good agreement for systolic pressure with only a slight underestimation of 1.9 mmHg and 5.1 mmHg lower for diastolic pressure. This difference most probably reflects inaccuracy of the auscultatory cuff method rather than an error in the Finapres. There was large inter-individual variability in Finapres recordings which might be due to differences in vasomotor tone, as demonstrated by systolic amplification in 5 patients with anorexia. However, Finapres showed a small within-subject variability (3.8 mmHg for systolic and 4.1 mmHg for diastolic pressure) determined in 5 patients during phenylephrine infusion, and as good reproducibility as the auscultatory method. These results suggest that finger arterial pressure measurement in children older than 6 years of age has similar accuracy as that in adults, and that this method is useful for clinical applications in children, especially for the non-invasive evaluation of autonomic control and cardiovascular reflexes involving transient and rapid blood pressure changes. PMID:7919764

  20. It Takes Two: Non Invasive Brain Stimulation Combined with Neurorehabilitation

    PubMed Central

    Page, Stephen J.; Cunningham, David A; Plow, Ela; Blazak, Brittani

    2015-01-01

    The goal of post-acute neurorehabilitation is to maximize patients' function, ideally by using surviving brain and central nervous system tissue when possible. Yet the structures incorporated into neurorehabilitative approaches often differ from this target, which may explain why efficacy of conventional clinical treatments targeting neurological impairments varies widely. Non-invasive brain stimulation such as with Transcranial Magnetic Stimulation (TMS) and transcranial direct current stimulation (tDCS) offers the possibility of directly targeting brain structures to facilitate or inhibit their activity so as to steer neural plasticity in recovery, and measure neuronal output and interactions for evaluating progress. Latest advances as stereotactic navigation and electric field modeling are enabling more precise targeting of patient's residual structures in diagnosis and therapy. Given its promise, this supplement illustrates the wide-ranging significance of TMS and tDCS in neurorehabilitation, including in stroke, pediatrics, traumatic brain injury, focal hand dystonia, neuropathic pain and spinal cord injury. TMS and tDCS are still not widely used and remain poorly understood in neurorehabilitation. Thus, the present supplement includes articles that highlight ready clinical application of these technologies, including their comparative diagnostic capabilities relative to neuroimaging, their therapeutic benefit, their optimal delivery, the stratification of likely responders, and the variable benefits associated with their clinical use due to interactions between pathophysiology and the innate reorganization of the patient's brain. Overall, the supplement concludes that whether provided in isolation or in combination, non-invasive brain stimulation with neuro-rehabilitation are synergistic in the potential to transform clinical practice. PMID:25813373

  1. Non-invasive assessment of microvascular and endothelial function.

    PubMed

    Cheng, Cynthia; Daskalakis, Constantine; Falkner, Bonita

    2013-01-01

    The authors have utilized capillaroscopy and forearm blood flow techniques to investigate the role of microvascular dysfunction in pathogenesis of cardiovascular disease. Capillaroscopy is a non-invasive, relatively inexpensive methodology for directly visualizing the microcirculation. Percent capillary recruitment is assessed by dividing the increase in capillary density induced by postocclusive reactive hyperemia (postocclusive reactive hyperemia capillary density minus baseline capillary density), by the maximal capillary density (observed during passive venous occlusion). Percent perfused capillaries represents the proportion of all capillaries present that are perfused (functionally active), and is calculated by dividing postocclusive reactive hyperemia capillary density by the maximal capillary density. Both percent capillary recruitment and percent perfused capillaries reflect the number of functional capillaries. The forearm blood flow (FBF) technique provides accepted non-invasive measures of endothelial function: The ratio FBF(max)/FBF(base) is computed as an estimate of vasodilation, by dividing the mean of the four FBF(max) values by the mean of the four FBFbase values. Forearm vascular resistance at maximal vasodilation (FVR(max)) is calculated as the mean arterial pressure (MAP) divided by FBF(max). Both the capillaroscopy and forearm techniques are readily acceptable to patients and can be learned quickly. The microvascular and endothelial function measures obtained using the methodologies described in this paper may have future utility in clinical patient cardiovascular risk-reduction strategies. As we have published reports demonstrating that microvascular and endothelial dysfunction are found in initial stages of hypertension including prehypertension, microvascular and endothelial function measures may eventually aid in early identification, risk-stratification and prevention of end-stage vascular pathology, with its potentially fatal

  2. Non-invasive glucose determination in the human eye

    NASA Astrophysics Data System (ADS)

    Schrader, Wolfgang; Meuer, Petra; Popp, Jürgen; Kiefer, Wolfgang; Menzebach, Johannes-Ulrich; Schrader, Bernhard

    2005-02-01

    For non-invasive in vivo glucose determinations by means of near-infrared spectroscopy, the anterior chamber of the human eye is a promising site. An optical set-up for the non-invasive glucose determination in the human eye precisely in the anterior chamber with a beam reflected from the surface of the eye lens is presented here. As the anterior chamber has a depth of 3.13±0.50 mm, the beam follows an optical path of 5.3-7.3 mm depending on the angle of incidence, which is individually constant. We will show that it is possible to acquire good concentration predictions for physiological glucose concentrations with such a long optical path. A chemometric study of NIR glucose spectra with concentrations of glucose in water of 10-350 mg/dL (0.56-1.94 mmol/L) resulted in a calibration model which was able to predict physiological glucose concentrations with a root mean square error of prediction RMSEPTest=15.41 mg/dL. The Clarke error grid diagram shows that the model performs well according to medical impact. Using a first in vivo set-up, the precision is not sufficient for a reliable prediction of glucose concentration, especially due to the flickering of the patient's eye and the low reflectivity of the eye lens. Therefore, we have designed a new in vivo set-up: a prototype for a self-monitoring device with controlled geometry and laser radiation at several distinct wavelengths instead of the halogen lamp as light source. This allows a far higher signal/noise ratio under much better reproducible geometrical conditions and at the same time a much smaller necessary light flux.

  3. Magnetocardiographic non-invasive localization of accessory pathways in the Wolff-Parkinson-White syndrome by a multichannel system.

    PubMed

    Weismüller, P; Abraham-Fuchs, K; Schneider, S; Richter, P; Kochs, M; Hombach, V

    1992-05-01

    Electrical activity can be localized by magnetocardiography (MCG) non-invasively. In this study a 37-SQUID (Super Conducting Quantum Interference Device) sensor multi-channel system (KRENIKON) was used to assess the potential of magnetocardiography to localize accessory pathways with a multichannel system. Seven WPW patients were studied by means of magnetocardiography. Prior to the MCG recordings, the site of the accessory pathway had been determined in all patients by invasive catheter mapping. MR images of the heart were used for anatomical correlation. The magnetocardiographic localization of the accessory pathway corresponded with catheter mapping within 2.1 cm on average (total range: 0-5 cm). This is thus, a promising new method for non-invasive localization of accessory pathways in WPW patients. PMID:1618202

  4. Silica-coated bismuth sulfide nanorods as multimodal contrast agents for a non-invasive visualization of the gastrointestinal tract

    NASA Astrophysics Data System (ADS)

    Zheng, Xiaopeng; Shi, Junxin; Bu, Yang; Tian, Gan; Zhang, Xiao; Yin, Wenyan; Gao, Bifen; Yang, Zhiyong; Hu, Zhongbo; Liu, Xiangfeng; Yan, Liang; Gu, Zhanjun; Zhao, Yuliang

    2015-07-01

    Non-invasive and real-time imaging of the gastrointestinal (GI) tract is particularly desirable for research and clinical studies of patients with symptoms arising from gastrointestinal diseases. Here, we designed and fabricated silica-coated bismuth sulfide nanorods (Bi2S3@SiO2 NRs) for a non-invasive spatial-temporally imaging of the GI tract. The Bi2S3 NRs were synthesized by a facile solvothermal method and then coated with a SiO2 layer to improve their biocompatibility and stability in the harsh environments of the GI tract, such as the stomach and the small intestine. Due to their strong X-ray- and near infrared-absorption abilities, we demonstrate that, following oral administration in mice, the Bi2S3@SiO2 NRs can be used as a dual-modal contrast agent for the real-time and non-invasive visualization of NRs distribution and the GI tract via both X-ray computed tomography (CT) and photoacoustic tomography (PAT) techniques. Importantly, integration of PAT with CT provides complementary information on anatomical details with high spatial resolution. In addition, we use Caenorhabditis Elegans (C. Elegans) as a simple model organism to investigate the biological response of Bi2S3@SiO2 NRs by oral administration. The results indicate that these NRs can pass through the GI tract of C. Elegans without inducing notable toxicological effects. The above results suggest that Bi2S3@SiO2 NRs pave an alternative way for the fabrication of multi-modal contrast agents which integrate CT and PAT modalities for a direct and non-invasive visualization of the GI tract with low toxicity.Non-invasive and real-time imaging of the gastrointestinal (GI) tract is particularly desirable for research and clinical studies of patients with symptoms arising from gastrointestinal diseases. Here, we designed and fabricated silica-coated bismuth sulfide nanorods (Bi2S3@SiO2 NRs) for a non-invasive spatial-temporally imaging of the GI tract. The Bi2S3 NRs were synthesized by a facile

  5. Enabling non-invasive assessment of an engineered endothelium on ePTFE vascular grafts without increasing oxidative stress.

    PubMed

    Jiang, Bin; Perrin, Louisiane; Kats, Dina; Meade, Thomas; Ameer, Guillermo

    2015-11-01

    Magnetic resonance imaging (MRI) in combination with contrast enhancement is a potentially powerful tool to non-invasively monitor cell distribution in tissue engineering and regenerative medicine. The most commonly used contrast agent for cell labeling is super paramagnetic iron oxide nanoparticles (SPIONs). However, uptake of SPIONs triggers the production of reactive oxygen species (ROS) in cells often leading to a pro-inflammatory phenotype. The objective of this study was to develop a labeling system to non-invasively visualize an engineered endothelium in vascular grafts without creating excessive oxidative stress. Specifically, we investigated: (1) chitosan-coated SPIONs (CSPIONs) as an antioxidant contrast agent for contrast enhancement, and (2) poly(1,8-octamethylene citrate) (POC) as an antioxidant interface to support cell adhesion and function of labeled cells on the vascular graft. While SPION-labeled endothelial cells (ECs) experienced elevated ROS formation and altered cell morphology, CSPION-labeled ECs cultured on POC-coated surfaces mitigated SPION-induced ROS formation and maintained EC morphology, phenotype, viability and functions. A monolayer of labeled ECs exhibited sufficient contrast with T2-weighed MR imaging. CSPION labeling of endothelial cells in combination with coating the graft wall with POC allows non-invasive monitoring of an engineered endothelium on ePTFE grafts without increasing oxidative stress. PMID:26283158

  6. Oncological image analysis: medical and molecular image analysis

    NASA Astrophysics Data System (ADS)

    Brady, Michael

    2007-03-01

    This paper summarises the work we have been doing on joint projects with GE Healthcare on colorectal and liver cancer, and with Siemens Molecular Imaging on dynamic PET. First, we recall the salient facts about cancer and oncological image analysis. Then we introduce some of the work that we have done on analysing clinical MRI images of colorectal and liver cancer, specifically the detection of lymph nodes and segmentation of the circumferential resection margin. In the second part of the paper, we shift attention to the complementary aspect of molecular image analysis, illustrating our approach with some recent work on: tumour acidosis, tumour hypoxia, and multiply drug resistant tumours.

  7. Non-invasive Chamber-Specific Identification of Cardiomyocytes in Differentiating Pluripotent Stem Cells

    PubMed Central

    Brauchle, Eva; Knopf, Anne; Bauer, Hannah; Shen, Nian; Linder, Sandra; Monaghan, Michael G.; Ellwanger, Kornelia; Layland, Shannon L.; Brucker, Sara Y.; Nsair, Ali; Schenke-Layland, Katja

    2016-01-01

    Summary One major obstacle to the application of stem cell-derived cardiomyocytes (CMs) for disease modeling and clinical therapies is the inability to identify the developmental stage of these cells without the need for genetic manipulation or utilization of exogenous markers. In this study, we demonstrate that Raman microspectroscopy can non-invasively identify embryonic stem cell (ESC)-derived chamber-specific CMs and monitor cell maturation. Using this marker-free approach, Raman peaks were identified for atrial and ventricular CMs, ESCs were successfully discriminated from their cardiac derivatives, a distinct phenotypic spectrum for ESC-derived CMs was confirmed, and unique spectral differences between fetal versus adult CMs were detected. The real-time identification and characterization of CMs, their progenitors, and subpopulations by Raman microspectroscopy strongly correlated to the phenotypical features of these cells. Due to its high molecular resolution, Raman microspectroscopy offers distinct analytical characterization for differentiating cardiovascular cell populations. PMID:26777059

  8. In situ non-invasive investigation on the painting techniques of early Meissen Stoneware

    NASA Astrophysics Data System (ADS)

    Miliani, Costanza; Doherty, Brenda; Daveri, Alessia; Loesch, Anette; Ulbricht, Heike; Brunetti, Brunetto G.; Sgamellotti, Antonio

    2009-08-01

    In situ, non-invasive investigations by means of portable X-ray fluorescence and fibre optic reflectance mid-infrared (mid-FTIR) spectroscopy of painted Böttger Stoneware objects have been carried out through the MOLAB transnational access to the Porcelain Collection of the Staatliche Kunstsammlungen in Dresden. It has been possible to gather information regarding the composition of the black glaze by applying a principal component analysis to the elemental analysis to distinguish between the variations of lead, iron and manganese compositions of each glaze. It has been furthermore feasible to combine molecular spectroscopy for characterization of the constituent painting materials, namely lead white as cerusite and hydrocerusite, the use of cinnabar, azurite and Prussian blue leading to a better knowledge of the state of conservation and utility of certain pigments that may give rise to chronology of the decorative artwork. The identification of oxalates namely whedellite and moolooite are assigned as degradation products relative to the decorative areas.

  9. MRI model-based non-invasive differential diagnosis in pulmonary hypertension.

    PubMed

    Lungu, A; Wild, J M; Capener, D; Kiely, D G; Swift, A J; Hose, D R

    2014-09-22

    Pulmonary hypertension(PH) is a disorder characterised by increased mean pulmonary arterial pressure. Currently, the diagnosis of PH relies upon measurements taken during invasive right heart catheterisation (RHC). This paper describes a process to derive diagnostic parameters using only non-invasive methods based upon MRI imaging alone. Simultaneous measurements of main pulmonary artery (MPA) anatomy and flow are interpreted by 0D and 1D mathematical models, in order to infer the physiological status of the pulmonary circulation. Results are reported for 35 subjects, 27 of whom were patients clinically investigated for PH and eight of whom were healthy volunteers. The patients were divided into 3 sub-groups according to the severity of the disease state, one of which represented a negative diagnosis (NoPH), depending on the results of the clinical investigation, which included RHC and complementary MR imaging. Diagnostic indices are derived from two independent mathematical models, one based on the 1D wave equation and one based on an RCR Windkessel model. Using the first model it is shown that there is an increase in the ratio of the power in the reflected wave to that in the incident wave (Wpb/Wptotal) according to the classification of the disease state. Similarly, the second model shows an increase in the distal resistance with the disease status. The results of this pilot study demonstrate that there are statistically significant differences in the parameters derived from the proposed models depending on disease status, and thus suggest the potential for development of a non-invasive, image-based diagnostic test for pulmonary hypertension. PMID:25145313

  10. Slug expression enhances tumor formation in a non-invasive rectal cancer model

    PubMed Central

    Camp, E. Ramsay; Findlay, Victoria J.; Vaena, Silvia G.; Walsh, Jarret; Lewin, David N.; Turner, David P.; Watson, Dennis K

    2011-01-01

    Background Epithelial-to-mesenchymal transition (EMT) is a series of molecular changes allowing epithelial cancer cells to acquire properties of mesenchymal cells: increased motility and invasion and protection from apoptosis. Transcriptional regulators such as Slug mediate EMT, working in part to repress E-cadherin transcription. We report a novel, non-invasive in vivo rectal cancer model to explore the role of Slug in colorectal cancer (CRC) tumor development. Methods For the generation of DLD-1 cells overexpressing Slug (Slug DLD-1), a Slug or empty (Empty DLD-1) pCMV-3Tag-1 (kanamycin resistant) vector was used for transfection. Cells were evaluated for Slug and E-cadherin expression, and cell migration and invasion. For the in vivo study, colon cancer cells (parental DLD-1, Slug DLD-1, empty DLD-1, and HCT-116) were submucosally injected into the posterior rectum of nude mice using endoscopic guidance. After 28 days, tumors were harvested and tissue was analyzed. Results Slug expression in our panel of colon cancer cell lines was inversely correlated with E-cadherin expression and enhanced migration/invasion. Slug DLD-1 cells demonstrated a 21-fold increased Slug and 19-fold decreased E-cadherin expression compared with empty DLD-1. Similarly, the Slug DLD-1 cells had significantly enhanced cellular migration and invasion. In the orthotopic rectal cancer model, Slug DLD-1 cells formed rectal tumors in 9/10 (90%) of the mice (mean volume = 458 mm3) compared with only 1/10 (10%) with empty DLD-1 cells. Conclusion Slug mediates EMT with enhanced in vivo rectal tumor formation. Our non-invasive in vivo model enables researchers to explore the molecular consequences of altered genes in a clinically relevant rectal cancer in an effort to develop novel therapeutic approaches for patients with rectal cancer. PMID:21470622

  11. Atomic force microscope, molecular imaging, and analysis.

    PubMed

    Chen, Shu-wen W; Teulon, Jean-Marie; Godon, Christian; Pellequer, Jean-Luc

    2016-01-01

    Image visibility is a central issue in analyzing all kinds of microscopic images. An increase of intensity contrast helps to raise the image visibility, thereby to reveal fine image features. Accordingly, a proper evaluation of results with current imaging parameters can be used for feedback on future imaging experiments. In this work, we have applied the Laplacian function of image intensity as either an additive component (Laplacian mask) or a multiplying factor (Laplacian weight) for enhancing image contrast of high-resolution AFM images of two molecular systems, an unknown protein imaged in air, provided by AFM COST Action TD1002 (http://www.afm4nanomedbio.eu/), and tobacco mosaic virus (TMV) particles imaged in liquid. Based on both visual inspection and quantitative representation of contrast measurements, we found that the Laplacian weight is more effective than the Laplacian mask for the unknown protein, whereas for the TMV system the strengthened Laplacian mask is superior to the Laplacian weight. The present results indicate that a mathematical function, as exemplified by the Laplacian function, may yield varied processing effects with different operations. To interpret the diversity of molecular structure and topology in images, an explicit expression for processing procedures should be included in scientific reports alongside instrumental setups. PMID:26224520

  12. Molecular Imaging of Experimental Abdominal Aortic Aneurysms

    PubMed Central

    Ramaswamy, Aneesh K.; Hamilton, Mark; Joshi, Rucha V.; Kline, Benjamin P.; Li, Rui; Wang, Pu; Goergen, Craig J.

    2013-01-01

    Current laboratory research in the field of abdominal aortic aneurysm (AAA) disease often utilizes small animal experimental models induced by genetic manipulation or chemical application. This has led to the use and development of multiple high-resolution molecular imaging modalities capable of tracking disease progression, quantifying the role of inflammation, and evaluating the effects of potential therapeutics. In vivo imaging reduces the number of research animals used, provides molecular and cellular information, and allows for longitudinal studies, a necessity when tracking vessel expansion in a single animal. This review outlines developments of both established and emerging molecular imaging techniques used to study AAA disease. Beyond the typical modalities used for anatomical imaging, which include ultrasound (US) and computed tomography (CT), previous molecular imaging efforts have used magnetic resonance (MR), near-infrared fluorescence (NIRF), bioluminescence, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). Mouse and rat AAA models will hopefully provide insight into potential disease mechanisms, and the development of advanced molecular imaging techniques, if clinically useful, may have translational potential. These efforts could help improve the management of aneurysms and better evaluate the therapeutic potential of new treatments for human AAA disease. PMID:23737735

  13. Molecular Imaging of Inflammation in Atherosclerosis

    PubMed Central

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

    2013-01-01

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

  14. Molecular Imaging Probe Development using Microfluidics

    PubMed Central

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

    2012-01-01

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

  15. In Vivo Molecular Imaging in Retinal Disease

    PubMed Central

    Xie, Fang; Luo, Wenting; Zhang, Zhongyu; Sun, Dawei

    2012-01-01

    There is an urgent need for early diagnosis in medicine, whereupon effective treatments could prevent irreversible tissue damage. The special structure of the eye provides a unique opportunity for noninvasive light-based imaging of ocular fundus vasculature. To detect endothelial injury at the early and reversible stage of adhesion molecule upregulation, some novel imaging agents that target retinal endothelial molecules were generated. In vivo molecular imaging has a great potential to impact medicine by detecting diseases or screening disease in early stages, identifying extent of disease, selecting disease and patient-specific therapeutic treatment, applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current preclinical findings and advances in instrumentation such as endoscopes and microcatheters suggest that these molecular imaging modalities have numerous clinical applications and will be translated into clinical use in the near future. PMID:22363836

  16. Use of perfluorocarbon nanoparticles for non-invasive multimodal cell tracking of human pancreatic islets

    PubMed Central

    Barnett, Brad P.; Ruiz-Cabello, Jesus; Hota, Partha; Ouwerkerk, Ronald; Shamblott, Michael J.; Lauzon, Cal; Walczak, Piotr; Gilson, Wesley D.; Chacko, Vadappuram P.; Kraitchman, Dara L.; Arepally, Aravind; Bulte, Jeff W. M.

    2011-01-01

    In vivo imaging of engraftment and immunorejection of transplanted islets is critical for further clinical development, with 1H MR imaging of superparamagnetic iron oxide-labeled cells being the current premier modality. Using perfluorocarbon nanoparticles, we present here a strategy for non-invasive imaging of cells using other modalities. To this end, human cadaveric islets were labeled with rhodamine-perfluorooctylbromide (PFOB) nanoparticles, rhodamine-perfluoropolyether (PFPE) nanoparticles or Feridex® as control and tested in vitro for cell viability and c-peptide secretion for 1 week. 19F MRI, computed tomography (CT) and ultrasound (US) imaging was performed on labeled cell phantoms and on cells following transplantation beneath the kidney capsule of mice and rabbits. PFOB and PFPE-labeling did not reduce human islet viability or glucose responsiveness as compared with unlabeled cells or SPIO-labeled cells. PFOB- and PFPE-labeled islets were effectively fluorinated for visualization by 19F MRI. PFOB-labeled islets were acoustically reflective for detection by US imaging and became sufficiently brominated to become radiopaque allowing visualization with CT. Thus, perfluorocarbon nanoparticles are multimodal cellular contrast agents that may find applications in real-time targeted delivery and imaging of transplanted human islets or other cells in a clinically applicable manner using MRI, US or CT imaging. PMID:21861285

  17. Simple non-invasive analysis of embryonic stem cell-derived cardiomyocytes beating in vitro

    NASA Astrophysics Data System (ADS)

    Radaszkiewicz, Katarzyna Anna; Sýkorová, Dominika; Karas, Pavel; Kudová, Jana; Kohút, Lukáš; Binó, Lucia; Večeřa, Josef; Víteček, Jan; Kubala, Lukáš; Pacherník, Jiří

    2016-02-01

    The analysis of digital video output enables the non-invasive screening of various active biological processes. For the monitoring and computing of the beating parameters of cardiomyocytes in vitro, CB Analyser (cardiomyocyte beating analyser) software was developed. This software is based on image analysis of the video recording of beating cardiomyocytes. CB Analyser was tested using cardiomyocytes derived from mouse embryonic stem cells at different stages of cardiomyogenesis. We observed that during differentiation (from day 18), the beat peak width decreased, which corresponded to the increased speed of an individual pulse. However, the beating frequency did not change. Further, the effects of epinephrine modulating mature cardiomyocyte functions were tested to validate the CB Analyser analysis. In conclusion, data show that CB Analyser is a useful tool for evaluating the functions of both developing and mature cardiomyocytes under various conditions in vitro.

  18. Fibre optic sensor for non-invasive monitoring of blood pressure during MRI scanning.

    PubMed

    Myllylä, Teemu S; Elseoud, Ahmed Abou; Sorvoja, Hannu S S; Myllylä, Risto A; Harja, Juha M; Nikkinen, Juha; Tervonen, Osmo; Kiviniemi, Vesa

    2011-01-01

    This report focuses on designing and implementing a non-invasive blood pressure (NIBP) measuring device capable of being used during magnetic resonance imaging (MRI). Based on measuring pulse wave velocity in arterial blood, the device uses the obtained result to estimate diastolic blood pressure. Pulse transit times are measured by two fibre optical accelerometers placed over the chest and carotid artery. The fabricated accelerometer contains two static fibres and a cantilever beam, whose free end is angled at 90 degrees to act as a reflecting surface. Optical fibres are used for both illuminating the surface and receiving the reflected light. When acceleration is applied to the sensor, it causes a deflection in the beam, thereby changing the amount of reflected light. The sensor's output voltage is proportional to the intensity of the reflected light. Tests conducted on the electronics and sensors inside an MRI room during scanning proved that the device is MR- compatible. No artifacts or distortions were detected. PMID:20401906

  19. [Amyotrophic neuralgia associated with bilateral phrenic paralysis treated with non-invasive mechanical ventilation].

    PubMed

    García García, María Del Carmen; Hernández Borge, Jacinto; Antona Rodríguez, María José; Pires Gonçalves, Pedro; García García, Gema

    2015-09-01

    Amyotrophic neuralgia is an uncommon neuropathy characterized by severe unilateral shoulder pain. Isolated or concomitant involvement of other peripheral motor nerves depending on the brachial plexus such as phrenic or laryngeal nerves is unusual(1). Its etiology is unknown, yet several explanatory factors have been proposed. Phrenic nerve involvement, either unilateral or bilateral, is exceedingly rare. Diagnosis relies on anamnesis, functional and imaging investigations and electromyogram. We report the case of a 48-year-old woman with a past history of renal transplantation due to proliferative glomerulonephritis with subsequent transplant rejection, who was eventually diagnosed with amyotrophic neuralgia with bilateral phrenic involvement, and who required sustained non-invasive mechanical ventilation. PMID:26049960

  20. Neurosonological Examination: A Non-Invasive Approach for the Detection of Cerebrovascular Impairment in AD

    PubMed Central

    Urbanova, Barbora; Tomek, Ales; Mikulik, Robert; Magerova, Hana; Horinek, Daniel; Hort, Jakub

    2014-01-01

    There has been a growing interest in vascular impairment associated with Alzheimer’s disease (AD). This interest was stimulated by the findings of higher incidence of vascular risk factors in AD. Signs of vascular impairment were investigated notably in the field of imaging methods. Our aim was to explore ultrasonographic studies of extra- and intracranial vessels in patients with AD and mild cognitive impairment (MCI) and define implications for diagnosis, treatment, and prevention of the disease. The most frequently studied parameters with extracranial ultrasound are intima-media thickness in common carotid artery, carotid atherosclerosis, and total cerebral blood flow. The transcranial ultrasound concentrates mostly on flow velocities, pulsatility indices, cerebrovascular reserve capacity, and cerebral microembolization. Studies suggest that there is morphological and functional impairment of cerebral circulation in AD compared to healthy subjects. Ultrasound as a non-invasive method could be potentially useful in identifying individuals in a higher risk of progression of cognitive decline. PMID:24478651

  1. Non-invasive sex assessment in bovine semen by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    De Luca, A. C.; Managó, S.; Ferrara, M. A.; Rendina, I.; Sirleto, L.; Puglisi, R.; Balduzzi, D.; Galli, A.; Ferraro, P.; Coppola, G.

    2014-05-01

    X- and Y-chromosome-bearing sperm cell sorting is of great interest, especially for animal production management systems and genetic improvement programs. Here, we demonstrate an optical method based on Raman spectroscopy to separate X- and Y-chromosome-bearing sperm cells, overcoming many of the limitations associated with current sex-sorting protocols. A priori Raman imaging of bull spermatozoa was utilized to select the sampling points (head-neck region), which were then used to discriminate cells based on a spectral classification model. Main variations of Raman peaks associated with the DNA content were observed together with a variation due to the sex membrane proteins. Next, we used principal component analysis to determine the efficiency of our device as a cell sorting method. The results (>90% accuracy) demonstrated that Raman spectroscopy is a powerful candidate for the development of a highly efficient, non-invasive, and non-destructive tool for sperm sexing.

  2. Non-invasive hyperthermia apparatus including coaxial applicator having a non-invasive radiometric receiving antenna incorporated therein and method of use thereof

    DOEpatents

    Ross, Michael P.

    1996-01-01

    A coaxial hyperthermia applicator for applying non-invasively electromagnetic energy to a body against which it is placed. The coaxial applicator antenna has formed integrally within it a non-invasive radiometric antenna for receiving thermoelectromagnetic emissions. The coaxial-configured applicator produces a bell-shaped radiation pattern symmetric about the axis of symmetry of the coaxial applicator. Integrating the radiometric antenna within the coaxial applicator produces a single device that performs dual functions. The first function is to transmit non-invasively energy for heating a subcutaneous tumor. The second function is to receive non-invasively thermal electromagnetic radiation from the tumor by which temperature is sensed and fed back to control the output of the coaxial applicator.

  3. Non-invasive hyperthermia apparatus including coaxial applicator having a non-invasive radiometric receiving antenna incorporated therein and method of use thereof

    DOEpatents

    Ross, M.P.

    1996-08-27

    A coaxial hyperthermia applicator is disclosed for applying non-invasively electromagnetic energy to a body against which it is placed. The coaxial applicator antenna has formed integrally within it a non-invasive radiometric antenna for receiving thermoelectromagnetic emissions. The coaxial-configured applicator produces a bell-shaped radiation pattern symmetric about the axis of symmetry of the coaxial applicator. Integrating the radiometric antenna within the coaxial applicator produces a single device that performs dual functions. The first function is to transmit non-invasively energy for heating a subcutaneous tumor. The second function is to receive non-invasively thermal electromagnetic radiation from the tumor by which temperature is sensed and fed back to control the output of the coaxial applicator. 11 figs.

  4. Molecular Imaging of Urogenital Diseases

    PubMed Central

    Cho, Steve Y.; Szabo, Zsolt; Morgan, Russell H.

    2013-01-01

    There is an expanding and exciting repertoire of PET imaging radiotracers for urogenital diseases, particularly in prostate cancer, renal cell cancer, and renal function. Prostate cancer is the most commonly diagnosed cancer in men. With growing therapeutics options for the treatment of metastatic and advanced prostate cancer, improved functional imaging of prostate cancer beyond the limitations of conventional computed tomography (CT) and bone scan (BS) is becoming increasingly important for both clinical management and drug development. PET radiotracers beyond 18F-Fluorodeoxyglucose (FDG) for prostate cancer include 18F-Sodium Fluoride, 11C-Choline and 18F-Fluorocholine and 11C-Acetate. Other emerging and promising PET radiotracers include a synthetic L-leucine amino acid analog (anti-18F-FACBC), dihydrotestosterone analog (18F-FDHT) and prostate specific membrane antigen (PSMA) based PET radiotracers (ex. 18F-DCFBC, 89Zr-DFO-J591, 68Ga(HBED-CC)). Larger prospective and comparison trials of these PET radiotracers are needed to establish the role of PET/CT in prostate cancer. Renal cell cancer imaging with FDG PET/CT although available can be limited, especially for detection of the primary tumor. Improved renal cell cancer detection with carbonic anhydrase IX (CAIX) based antibody (124I-girentuximab) and radioimmunotherapy targeting with 177Lu-cG250 appear promising. Evaluation of renal injury by imaging renal perfusion and function with novel PET radiotracers include p-18F-fluorohippurate (18F-PFH) and hippurate m-cyano-p-18F-fluorohippurate (18F-CNPFH) and Rubidium-82 chloride (typically used for myocardial perfusion imaging). Renal receptor imaging of the renal renin angiotensin system with a variety of selective PET radioligands are also becoming available for clinical translation. PMID:24484747

  5. Tissue Damage Characterization Using Non-invasive Optical Modalities

    NASA Astrophysics Data System (ADS)

    Diaz, David

    The ability to determine the degree of cutaneous and subcutaneous tissue damage is essential for proper wound assessment and a significant factor for determining patient treatment and morbidity. Accurate characterization of tissue damage is critical for a number of medical applications including surgical removal of nonviable tissue, severity assessment of subcutaneous ulcers, and depth assessment of visually open wounds. The main objective of this research was to develop a non-invasive method for identifying the extent of tissue damage underneath intact skin that is not apparent upon visual examination. This work investigated the relationship between tissue optical properties, blood flow, and tissue viability by testing the hypotheses that (a) changes in tissue oxygenation and/or microcirculatory blood flow measurable by Diffuse Near Infrared Spectroscopy (DNIRS) and Diffuse Correlation Spectroscopy (DCS) differ between healthy and damaged tissue and (b) the magnitude of those changes differs for different degrees of tissue damage. This was accomplished by developing and validating a procedure for measuring microcirculatory blood flow and tissue oxygenation dynamics at multiple depths (up to 1 centimeter) using non-invasive DCS and DNIRS technologies. Due to the lack of pressure ulcer animal models that are compatible with our optical systems, a proof of concept was conducted in a porcine burn model prior to conducting clinical trials in order to assess the efficacy of the system in-vivo. A reduction in total hemoglobin was observed for superficial (5%) and deep burns (35%) along with a statistically significant difference between the optical properties of superficial and deep burns (p < 0.05). Burn depth and viable vessel density were estimated via histological samples. 42% of vessels in the dermal layer were viable for superficial burns, compared to 25% for deep burns. The differences detected in optical properties and hemoglobin content by optical measurements

  6. Non-invasive shallow seismic source comparison for hazardous waste site investigations

    SciTech Connect

    Doll, W.E.; Miller, R.D.; Xia, J.

    1994-12-31

    Many commonly used shallow seismic sources are unacceptable for hazardous waste site investigations because they risk exhumation of contaminants in the soil, they add contaminants (e.g. lead) which are not allowed by regulations, or they add new migration paths for contaminants. Furthermore, recently developed high frequency vibrators for shallow investigations could be more effective at some sites than non-invasive impulsive sources because of their ability to tailor the source spectrum and reduce interference. The authors show preliminary results of a comparison test of eight non-invasive impulsive and swept sources in preparation for seismic reflection profiling on the Oak Ridge Reservation, Tennessee. Well log data are used to determine geologic contacts and to generate synthetic seismograms for the site. Common midpoint (CMP) seismic data for each source were collected at 95 geophone groups from 125 shot points along a 400m test line. Hydrophone data were obtained at 1.5m spacing between 61m and 133m depth in a hole near the center of the CMP line. As of March, 1994, brute stacks have been completed for three of the eight sources. Depth penetration is demonstrated in brute stacks and shot gathers, which show a 200ms reflector for all of the sources tested along portions of the line. Source effectiveness will also be evaluated by comparing images of several shallower reflectors (40--150ms) which are apparent in many of the records. Imaging of these reflectors appears to depend upon the ability of the source to generate sufficient high frequency energy (>100 Hz).

  7. Molecular and Functional Imaging of Internet Addiction

    PubMed Central

    Zhu, Yunqi; Zhang, Hong; Tian, Mei

    2015-01-01

    Maladaptive use of the Internet results in Internet addiction (IA), which is associated with various negative consequences. Molecular and functional imaging techniques have been increasingly used for analysis of neurobiological changes and neurochemical correlates of IA. This review summarizes molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI) and nuclear imaging modalities including positron emission tomography (PET) and single photon emission computed tomography (SPECT). MRI studies demonstrate that structural changes in frontal cortex are associated with functional abnormalities in Internet addicted subjects. Nuclear imaging findings indicate that IA is associated with dysfunction of the brain dopaminergic systems. Abnormal dopamine regulation of the prefrontal cortex (PFC) could underlie the enhanced motivational value and uncontrolled behavior over Internet overuse in addicted subjects. Further investigations are needed to determine specific changes in the Internet addictive brain, as well as their implications for behavior and cognition. PMID:25879023

  8. Non-invasive Technology to Study Local Passivity Breakdown of Metal Alloys in Aqueous Media

    SciTech Connect

    Alan M. Shipley

    2005-03-09

    Little is known about the basic mechanisms of passive oxide breakdown, repair, and localized corrosion of metals. A non-invasive instrument and methods have been developed to study local events and mechanisms that initiate passivity breakdown and subsequent corrosion of metals in aqueous media. The ''difference viewer imaging technique'' (DVIT) is a rapid, real time, non-invasive assay to study metal surfaces in corrosive solutions. It has a spatial resolution of less than 10.0 ?m (1cm x 1cm sample, 1000 x 1000 pixel CCD) to observe initial corrosion processes of the order of seconds. DVIT is a software-controlled video microscopy system and methods to collect and analyze pixel changes in video images. These images are recorded from a digital CCD video camera and frame grabber package using visible light for illumination. The DVIT system detects changes in video images that represent initial corrosive events that lead to passivity breakdown and re-passivation on metal surfaces in situ. This visual technique is easy to use and apply. It compliments other metal surface measurement techniques and can be used simultaneously with them. DVIT has proven to be more sensitive in detecting changes than scanning microelectrode techniques. DVIT is also much easier than other methods to apply and operate. It has the further advantage of providing a real time image of the entire metal surface under study instead of waiting for a microelectrode to scan a number of data points over a sample then plot the results. This project has fulfilled all specifications as outlined in the Department of Energy solicitation responsible for this grant application and award and exceeded a number of the specifications. Applicable Electronics, Inc. now has a marketable instrument and software package available for sale now. Further development of the system will be ongoing as driven by customer needs and discoveries. This technology has immediate applications in corrosion labs to further study

  9. A Non-invasive Platform for Functional Characterization of Stem-Cell-Derived Cardiomyocytes with Applications in Cardiotoxicity Testing

    PubMed Central

    Maddah, Mahnaz; Heidmann, Julia D.; Mandegar, Mohammad A.; Walker, Chase D.; Bolouki, Sara; Conklin, Bruce R.; Loewke, Kevin E.

    2015-01-01

    Summary We present a non-invasive method to characterize the function of pluripotent stem-cell-derived cardiomyocytes based on video microscopy and image analysis. The platform, called Pulse, generates automated measurements of beating frequency, beat duration, amplitude, and beat-to-beat variation based on motion analysis of phase-contrast images captured at a fast frame rate. Using Pulse, we demonstrate recapitulation of drug effects in stem-cell-derived cardiomyocytes without the use of exogenous labels and show that our platform can be used for high-throughput cardiotoxicity drug screening and studying physiologically relevant phenotypes. PMID:25801505

  10. Non-invasive integrative analysis of contraction energetics in intact beating heart.

    PubMed

    Deschodt-Arsac, Véronique; Calmettes, Guillaume; Gouspillou, Gilles; Chapolard, Mathilde; Raffard, Gérard; Rouland, Richard; Jais, Pierre; Haissaguerre, Michel; Dos Santos, Pierre; Diolez, Philippe

    2013-01-01

    The comprehensive study of human pathologies has revealed the complexity of the interactions involved in cardiovascular physiology. The recent validation of system's biology approaches - like our Modular Control and Regulation Analysis (MoCA) - motivates the current interest for new integrative and non-invasive analyses that could be used for medical study of human heart contraction energetics. By considering heart energetics as a supply-demand system, MoCA gives access to integrated organ function and brings out a new type of information, the "elasticities", which describe in situ the regulation of both energy demand and supply by cellular energetic status. These regulations determine the internal control of contraction energetics and may therefore be a key to the understanding of the links between molecular events in pathologies and whole organ function/dysfunction. A wider application to the effects of cardiac drugs in conjunction with the direct study of heart pathologies may be considered in the near future. MoCA can potentially be used not only to detect the origin of the defects associated with the pathology (elasticity analyses), but also to provide a quantitative description of how these defects influence global heart function (regulation analysis) and therefore open new therapeutic perspectives. Several key examples of current applications to intact isolated beating heart are presented in this paper. The future application to human pathologies will require the use of non-invasive NMR techniques for the simultaneous measurement of energy status ((31)P NMR) and heart contractile activity (3D MRI). This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. PMID:22789933

  11. Non-invasive experimental determination of a CT source model.

    PubMed

    Alikhani, Babak; Büermann, Ludwig

    2016-01-01

    Non-invasive methods to determine equivalent X-ray source models of a CT scanner are presented. A high-precision technique called TRIC ("Time Resolved Integrated Charge") was developed and used to characterize the bow tie filters (BT) of the CT scanner installed at Physikalisch-Technische Bundesanstalt (PTB). Aluminum (Al) and polymethyl methacrylate (PMMA) equivalent thicknesses of the BT filters at all tube high voltages were evaluated, assuming that those consist of only one material. Thereby two different dose probes were used, a solid state detector and an ionization chamber, the former characterized by a significant and the latter by an almost negligible energy dependence of the air kerma response. A method was developed to correct for the energy dependence of the solid state dose probe. Next, a two-component material was assumed and equivalent BT filters were evaluated. The latter method was also applied using the known real BT filter materials and compared with the shape of the real BT filters. Finally, the results obtained by the TRIC method were compared with those obtained by using the so-called COBRA method ("Characterization Of Bow tie Relative Attenuation"), the latter being more suitable for measurements in a clinical environment. PMID:26602858

  12. Alteration of Political Belief by Non-invasive Brain Stimulation

    PubMed Central

    Chawke, Caroline; Kanai, Ryota

    2016-01-01

    People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to. PMID:26834603

  13. Non-invasive Renal Denervation: Update on External Ultrasound Approaches.

    PubMed

    Schmieder, Roland E; Ott, Christian; Bramlage, Peter

    2016-06-01

    In the last decade, intravenous renal denervation (RDN) has emerged as an alternative to pharmacological treatment in patients with resistant hypertension, but currently involves an invasive and technically challenging procedure. The Surround Sound™ system utilises externally delivered ultrasound to achieve RDN using a completely non-invasive, automated real-time tracking system coupled with a therapeutic delivery module thereby addressing these limitations. A brief history, technical overview and summary of preclinical and clinical studies of the KonaMedical Surround Sound™ system are presented. A literature search using the terms "renal denervation", "resistant hypertension" and "external ultrasound" was performed using PubMed, and references retrieved were selected based on relevancy and year of publication (date range 1991-2015). The Surround Sound™ system appears to be a promising approach to RDN which eliminates several of the factors currently limiting the intravenous approach. So far, it has demonstrated efficacy for reducing blood pressure in resistant hypertension patients with minimal adverse effects. Several double-blind, sham-controlled clinical trials are currently underway to confirm the validity of these findings. PMID:27137523

  14. Non-Invasive Gait Monitoring in a Ubiquitous Computing House

    NASA Astrophysics Data System (ADS)

    Ohta, Yuji; Motooka, Nobuhisa; Siio, Itiro; Tsukada, Koji; Kambara, Keisuke

    Computers become smaller and cheaper from day to day, and the utilization, as daily life equipments, is now becoming ubiquitous. Therefore, it's essential to discuss the development of applications, as well as the installation of ubiquitous computing technologies into our daily living environments. Based on this idea, in order to investigate how ubiquitous computing can be used in the most efficient way, an experimental house, Ocha House, has been constructed in the campus of Ochanomizu university in 2009. In this study, we described the feature of the design of the experimental house and proposed a non-invasive gait monitoring technique as a healthcare application. Specifically, five wireless accelerometers were fixed on the floor of the house, and the floor vibration was measured when the subject walked along the accelerometers. As a result, the floor acceleration intensity was found to surge at the ground contact, and the gait cycle could be detected. By combining the simple acceleration sensors and the housing structures, human motion monitoring would become less invasive.

  15. Public viewpoints on new non-invasive prenatal genetic tests.

    PubMed

    Farrimond, Hannah R; Kelly, Susan E

    2013-08-01

    Prenatal screening programmes have been critiqued for their routine implementation according to clinical rationale without public debate. A new approach, non-invasive prenatal diagnosis (NIPD), promises diagnosis of fetal genetic disorders from a sample of maternal blood without the miscarriage risk of current invasive prenatal tests (e.g. amniocentesis). Little research has investigated the attitudes of wider publics to NIPD. This study used Q-methodology, which combines factor analysis with qualitative comments, to identify four distinct "viewpoints" amongst 71 UK men and women: 1. NIPD as a new tool in the ongoing societal discrimination against the disabled; 2. NIPD as a positive clinical application offering peace of mind in pregnancy; 3. NIPD as a medical option justified for severe disorders only; and 4. NIPD as a valid expansion of personal choice. Concerns included the "trivialisation of testing" and the implications of commercial/direct-to-consumer tests. Q-methodology has considerable potential to identify viewpoints and frame public debate about new technologies. PMID:23885055

  16. Non-Invasive Measurement of Intracranial Pressure Pulsation using Ultrasound

    NASA Technical Reports Server (NTRS)

    Ueno, Toshiaki; Ballard, R. E.; Yost, W. T.; Hargens, A. R.

    1997-01-01

    Exposure to microgravity causes a cephalad fluid shift which may elevate intracranial pressure (ICP). Elevation in ICP may affect cerebral hemodynamics in astronauts during space flight. ICP is, however, a difficult parameter to measure due to the invasiveness of currently available techniques. We already reported our development of a non-invasive ultrasound device for measurement of ICP. We recently modified the device so that we might reproducibly estimate ICP changes in association with cardiac cycles. In the first experiment, we measured changes in cranial distance with the ultrasound device in cadavera while changing ICP by infusing saline into the lateral ventricle. In the second experiment, we measured changes in cranial distance in five healthy volunteers while placing them in 60 deg, 30 deg head-up tilt, supine, and 10 deg head-down tilt position. In the cadaver study, fast Fourier transformation revealed that cranial pulsation is clearly associated with ICP pulsation. The ratio of cranial distance and ICP pulsation is 1.3microns/mmHg. In the tilting study, the magnitudes of cranial pulsation are linearly correlated to tilt angles (r=0.87). The ultrasound device has sufficient sensitivity to detect cranial pulsation in association with cardiac cycles. By analyzing the magnitude of cranial pulsation, estimates of ICP during space flight are possible.

  17. Non-invasive biosensor and wilreless interrogating system for hypoglycemia

    NASA Astrophysics Data System (ADS)

    Varadan, Vijay K.; Whitchurch, Ashwin K.; Saukesi, K.

    2002-11-01

    Hypoglycemia - abnormal decrease in blood sugar - is a major obstacle in the management of diabetes and prevention of long-term complications, and it may impose serious effects on the brain, including impairment of memory and other cognitive functions. This paper presents the development of a non-invasive sensor with miniaturized telemetry device in a wrist-watch for monitoring glucose concentration in blood. The sensor concept is based on optical chiralit of glucose level in the interstitial fluid. The wrist watch consists of a laser power source of the wavelength compatible with the glucose. A nanofilm with specific chirality is placed at the bottom of the watch. The light then passes through the film and illuminates a small area on the skin.It has been documented that there is certain concentration of sugar level is taken by the intertitial fluid from the blood stream and deposit a portion of it at the dead skin. The wrist-watch when in contact with the outer skin of the human will thus monitor the glucose concentration. A wireless monitoring system in the watch then downloads the data from the watch to a Palm or laptop computer.

  18. Alteration of Political Belief by Non-invasive Brain Stimulation.

    PubMed

    Chawke, Caroline; Kanai, Ryota

    2015-01-01

    People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to. PMID:26834603

  19. A non-invasive method of tendon force measurement.

    PubMed

    Pourcelot, Philippe; Defontaine, Marielle; Ravary, Bérangère; Lemâtre, Mickaël; Crevier-Denoix, Nathalie

    2005-10-01

    The ability to measure the forces exerted in vivo on tendons and, consequently, the forces produced by muscles on tendons, offers a unique opportunity to investigate questions in disciplines as varied as physiology, biomechanics, orthopaedics and neuroscience. Until now, tendon loads could be assessed directly only by means of invasive sensors implanted within or attached to these collagenous structures. This study shows that the forces acting on tendons can be measured, in a non-invasive way, from the analysis of the propagation of an acoustic wave. Using the equine superficial digital flexor tendon as a model, it is demonstrated that the velocity of an ultrasonic wave propagating along the main axis of a tendon increases with the force applied to this tendon. Furthermore, we show that this velocity measurement can be performed even in the presence of skin overlying the tendon. To validate this measurement technique in vivo, the ultrasonic velocity plots obtained in the Achilles tendon at the walk were compared to the loads plots reported by other authors using invasive transducers. PMID:16084214

  20. Reducing proactive aggression through non-invasive brain stimulation.

    PubMed

    Dambacher, Franziska; Schuhmann, Teresa; Lobbestael, Jill; Arntz, Arnoud; Brugman, Suzanne; Sack, Alexander T

    2015-10-01

    Aggressive behavior poses a threat to human collaboration and social safety. It is of utmost importance to identify the functional mechanisms underlying aggression and to develop potential interventions capable of reducing dysfunctional aggressive behavior already at a brain level. We here experimentally shifted fronto-cortical asymmetry to manipulate the underlying motivational emotional states in both male and female participants while assessing the behavioral effects on proactive and reactive aggression. Thirty-two healthy volunteers received either anodal transcranial direct current stimulation to increase neural activity within right dorsolateral prefrontal cortex, or sham stimulation. Aggressive behavior was measured with the Taylor Aggression Paradigm. We revealed a general gender effect, showing that men displayed more behavioral aggression than women. After the induction of right fronto-hemispheric dominance, proactive aggression was reduced in men. This study demonstrates that non-invasive brain stimulation can reduce aggression in men. This is a relevant and promising step to better understand how cortical brain states connect to impulsive actions and to examine the causal role of the prefrontal cortex in aggression. Ultimately, such findings could help to examine whether the brain can be a direct target for potential supportive interventions in clinical settings dealing with overly aggressive patients and/or violent offenders. PMID:25680991

  1. Non-invasive fecal metabonomic detection of colorectal cancer

    PubMed Central

    Phua, Lee Cheng; Chue, Xiu Ping; Koh, Poh Koon; Cheah, Peh Yean; Ho, Han Kiat; Chan, Eric Chun Yong

    2014-01-01

    Colorectal cancer (CRC) is a major cause of mortality in many developed countries. Effective screening strategies were called for to facilitate timely detection and to promote a better clinical outcome. In this study, the role of fecal metabonomics in the non-invasive detection of CRC was investigated. Gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) was utilized for the metabolic profiling of feces obtained from 11 CRC patients and 10 healthy subjects. Concurrently, matched tumor and normal mucosae surgically excised from CRC patients were profiled. CRC patients were differentiated clearly from healthy subjects based on their fecal metabonomic profiles (orthogonal partial least squares discriminant analysis [OPLS-DA], 1 predictive and 3 Y-orthogonal components, R2X = 0.373, R2Y = 0.995, Q2 [cumulative] = 0.215). The robustness of the OPLS-DA model was demonstrated by an area of 1 under the receiver operator characteristic curve. OPLS-DA revealed fecal marker metabolites (e.g., fructose, linoleic acid, and nicotinic acid) that provided novel insights into the tumorigenesis of CRC. Interestingly, a disparate set of CRC-related metabolic aberrations occurred at the tissue level, implying the contribution of processes beyond the direct shedding of tumor cells to the fecal metabotype. In summary, this work established proof-of-principle for GC/TOFMS-based fecal metabonomic detection of CRC and offered new perspectives on the underlying mechanisms. PMID:24424155

  2. Non-invasive instant genotyping of fluorescently labelled transgenic mice.

    PubMed

    Fink, Dieter; Yau, Tien Yin; Kolbe, Thomas; Rülicke, Thomas

    2015-01-01

    Fluorescence proteins have been useful as genetic reporters for a wide range of applications in biomedical research and are frequently used for the analysis of transgene activity. Here, we show that expression levels of the ubiquitously expressed fluorescent proteins eGFP, mCherry, and tdTomato can be measured in transgenic mouse lines with random or targeted integrations. We identified the tail of the mouse as the tissue best suited for quantifying fluorescence intensity and show that expression levels in the tail correlate with gene dose. This allows for instant non-invasive determination of the genetic condition at the transgenic locus (hemizygous/heterozygous and homozygous), while simultaneously providing an objective comparison for transgene expression levels among different mouse lines. In summary, we demonstrate for the first time that the gene dose of a ubiquitously expressed fluorescence reporter can be reliably quantified and directly linked to the genotype of transgenic mice. Based on this information, animals with the appropriate genotype can be instantly selected without laborious analysis for establishing and breeding of new transgenic lines, reducing the number of "waste" animals. Furthermore, no tissue sampling is necessary, which is a significant refinement of genotyping procedures. Both aspects are important improvements for the genotyping of transgenic mice that follow the principles of the 3 Rs (reduction and refinement). PMID:25981046

  3. Non-invasive prenatal screening for trisomy 21: Consumers' perspectives.

    PubMed

    Higuchi, Emily C; Sheldon, Jane P; Zikmund-Fisher, Brian J; Yashar, Beverly M

    2016-02-01

    Non-invasive prenatal screening (NIPS) has the potential to dramatically increase the prenatal detection rate of Down syndrome because of improvements in safety and accuracy over existing tests. There is concern that NIPS could lead to more negative attitudes towards Down syndrome and less support for individuals with Down syndrome. To assess the impact of NIPS on support for prenatal testing, decision-making about testing, and beliefs or attitudes about Down syndrome, we performed an Internet-based experiment using adults (N = 1,789) recruited through Amazon Mechanical Turk. Participants were randomly assigned to read a mock news article about NIPS, a mock news article about amniocentesis, or no article. The content in the two articles varied only in their descriptions of the test characteristics. Participants then answered questions about their support for testing, hypothetical testing decision, and beliefs and attitudes about Down syndrome. Reading the mock NIPS news article predicted increased hypothetical test uptake. In addition, the NIPS article group also agreed more strongly that pregnant women, in general, should utilize prenatal testing. We also found that the more strongly participants supported prenatal testing for pregnant women, the less favorable their attitudes towards individuals with Down syndrome; providing some evidence that NIPS may indirectly result in more negative perceptions of individuals with this diagnosis. PMID:26553705

  4. Use of dexmedetomidine to facilitate non-invasive ventilation

    PubMed Central

    DeMuro, Jonas P; Mongelli, Michael N; Hanna, Adel F

    2013-01-01

    Patients with chronic obstructive pulmonary disease and congestive heart failure exacerbations, as well as pneumonia benefit from the use of non-invasive ventilation (NIV), due to increased patient comfort and a reduced incidence of ventilator-associated pneumonia. However, some patients do not tolerate NIV due to anxiety or agitation, and traditionally physicians have withheld sedation from these patients due to concerns of loss of airway protection and respiratory depression. We report our recent experience with a 91-year-old female who received NIV for acute respiratory distress secondary to pneumonia. The duration of NIV was a total time period of 86 h, using the bilevel positive airway pressure mode via a full face mask. The patient was initially agitated with the NIV, but with the addition of the dexmedetomidine, she tolerated it well. The dexmedetomidine was administered without a loading dose, as a continuous infusion ranging from 0.2 to 0.5 mcg/kg/hr, titrated to a Ramsey score of three. This case illustrates the safe use of dexmedetomidine to facilitate NIV, and improve compliance, which may reduce ICU length of stay. PMID:24459626

  5. Novel non-invasive protein and peptide drug delivery approaches.

    PubMed

    Wallis, L; Kleynhans, E; Toit, T Du; Gouws, C; Steyn, D; Steenekamp, J; Viljoen, J; Hamman, J

    2014-01-01

    Protein and peptide based therapeutics are typically administered by injection due to their poor uptake when administered via enteral routes of drug administration. Unfortunately, chronic administration of these drugs through multiple injections presents certain patient related problems and it is difficult to mimic the normal physiological release patterns via this mode of drug administration. A need therefore exists to non-invasively deliver these drugs by means of alternative ways such as via the oral, pulmonary, nasal, transdermal and buccal administration routes. Although some attempts of needle free peptide and protein drug delivery have progressed to the clinical stage, relatively limited success has been achieved in terms of commercially available products. Despite the low frequency of clinical breakthroughs with noninvasive protein drug delivery this far, it remains an active research area with renewed interest not only due to its improved therapeutic potential, but also due to the attractive commercial outcomes it offers. It is the aim of this review article to reflect on the main strategies investigated to overcome the barriers against effective systemic protein drug delivery in different routes of drug administration. Approaches based on chemical modifications and pharmaceutical technologies are discussed with reference to examples of drugs and devices that have shown potential, while attempts that have failed are also briefly outlined. PMID:25106909

  6. Non-invasive mechanical ventilation and epidural anesthesia for an emergency open cholecystectomy.

    PubMed

    Yurtlu, Bülent Serhan; Köksal, Bengü; Hancı, Volkan; Turan, Işıl Özkoçak

    2016-01-01

    Non-invasive ventilation is an accepted treatment modality in both acute exacerbations of respiratory diseases and chronic obstructive lung disease. It is commonly utilized in the intensive care units, or for postoperative respiratory support in post-anesthesia care units. This report describes intraoperative support in non-invasive ventilation to neuroaxial anesthesia for an emergency upper abdominal surgery. PMID:27591472

  7. Caught in the act: In vivo molecular imaging of the transcription factor NF-{kappa}B after myocardial infarction

    SciTech Connect

    Tillmanns, Jochen; Carlsen, Harald; Blomhoff, Rune; Valen, Guro; Calvillo, Laura; Ertl, Georg; Bauersachs, Johann; Frantz, Stefan . E-mail: frantz_s@medizin.uni-wuerzburg.de

    2006-04-14

    Nuclear factor {kappa}B (NF-{kappa}B) is a ubiquitous transcription factor activated by various stimuli implicated in heart failure progression. However, its activation in heart failure has not been well defined yet. Therefore, we investigated activation of NF-{kappa}B after myocardial infarction. For First time, we performed serial, non-invasive in vivo molecular imaging of transcription factor activation in the heart. We used mice expressing a luciferase reporter whose transcription is dependent upon NF-{kappa}B activation for up to 8 weeks after myocardial infarction. There was a significant increase of NF-{kappa}B activity with a maximum at day 3 after myocardial infarction when compared to sham controls. Thus, in vivo measurement of the activation of NF-{kappa}B is feasible. NF-{kappa}B activity might play an important role for the remodeling process.

  8. Non-invasive quantification of lower limb mechanical alignment in flexion

    PubMed Central

    Deakin, Angela; Fogg, Quentin A.; Picard, Frederic

    2014-01-01

    Objective Non-invasive navigation techniques have recently been developed to determine mechanical femorotibial alignment (MFTA) in extension. The primary aim of this study was to evaluate the precision and accuracy of an image-free navigation system with new software designed to provide multiple kinematic measurements of the knee. The secondary aim was to test two types of strap material used to attach optical trackers to the lower limb. Methods Seventy-two registrations were carried out on 6 intact embalmed cadaveric specimens (mean age: 77.8 ± 12 years). A validated fabric strap, bone screws and novel rubber strap were used to secure the passive tracker baseplate for four full experiments with each knee. The MFTA angle was measured under the conditions of no applied stress, valgus stress, and varus stress. These measurements were carried out at full extension and at 30°, 40°, 50° and 60° of flexion. Intraclass correlation coefficients, repeatability coefficients, and limits of agreement (LOA) were used to convey precision and agreement in measuring MFTA with respect to each of the independent variables, i.e., degree of flexion, applied coronal stress, and method of tracker fixation. Based on the current literature, a repeatability coefficient and LOA of ≤3° were deemed acceptable. Results The mean fixed flexion for the 6 specimens was 12.8° (range: 6–20°). The mean repeatability coefficient measuring MFTA in extension with screws or fabric strapping of the baseplate was ≤2°, compared to 2.3° using rubber strapping. When flexing the knee, MFTA measurements taken using screws or fabric straps remained precise (repeatability coefficient ≤3°) throughout the tested range of flexion (12.8–60°); however, using rubber straps, the repeatability coefficient was >3° beyond 50° flexion. In general, applying a varus/valgus stress while measuring MFTA decreased precision beyond 40° flexion. Using fabric strapping, excellent repeatability

  9. Molecular Imaging with SERS-Active Nanoparticles

    PubMed Central

    Zhang, Yin; Hong, Hao; Myklejord, Duane V.; Cai, Weibo

    2011-01-01

    Lead-in Raman spectroscopy has been explored for various biomedical applications (e.g. cancer diagnosis) because it can provide detailed information on the chemical composition of cells and tissues. For imaging applications, several variations of Raman spectroscopy have been developed to enhance its sensitivity. To date, a wide variety of molecular targets and biological events have been investigated using surface-enhanced Raman scattering (SERS)-active nanoparticles. The superb multiplexing capability of SERS-based Raman imaging, already successfully demonstrated in live animals, can be extremely powerful in future research where different agents can be attached to different Raman tags to enable the simultaneous interrogation of multiple biological events. Over the last several years, molecular imaging with SERS-active nanoparticles has advanced significantly and many pivotal proof-of-principle experiments have been successfully carried out. It is expected that SERS-based imaging will continue to be a dynamic research field over the next decade. PMID:21932216

  10. Molecular imaging of cerebrovascular lesions.

    PubMed

    Chalouhi, Nohra; Jabbour, Pascal; Magnotta, Vincent; Hasan, David

    2014-04-01

    Inflammation is a key component in the pathogenesis of cerebrovascular lesions. Two agents have emerged as promising possibilities for imaging cerebrovascular lesions. These agents are ferumoxytol and myeloperoxidase (MPO)-specific paramagnetic magnetic resonance (MR) contrast agent. Ferumoxytol is an iron oxide nanoparticle coated by a carbohydrate shell that is used in MRI studies as an inflammatory marker as it is cleared by macrophages. Ferumoxytol-enhanced MRI allows noninvasive assessment of the inflammatory status of cerebral aneurysms and arteriovenous malformations and, possibly, may differentiate "unstable" lesions that require early intervention from "stable" lesions that can be safely observed. Several pilot studies have also suggested that MPO-specific paramagnetic MR contrast agent, di-5-hydroxytryptamide of gadopentetate dimeglumine, may allow imaging of inflammation in the wall of saccular aneurysms in animal models. However, studies in human subjects have yet to be performed. In this paper, we review current data regarding ferumoxytol-enhanced MRI and MPO-specific paramagnetic MR contrast agent and discuss current and future applications. PMID:24323714

  11. Microwave radiometry for non-invasive detection of vesicoureteral reflux (VUR) following bladder warming

    NASA Astrophysics Data System (ADS)

    Stauffer, Paul R.; Maccarini, Paolo F.; Arunachalam, Kavitha; De Luca, Valeria; Salahi, Sara; Boico, Alina; Klemetsen, Oystein; Birkelund, Yngve; Jacobsen, Svein K.; Bardati, Fernando; Tognolotti, Piero; Snow, Brent

    2011-03-01

    Background: Vesicoureteral reflux (VUR) is a serious health problem leading to renal scarring in children. Current VUR detection involves traumatic x-ray imaging of kidneys following injection of contrast agent into bladder via invasive Foley catheter. We present an alternative non-invasive approach for detecting VUR by radiometric monitoring of kidney temperature while gently warming the bladder. Methods: We report the design and testing of: i) 915MHz square slot antenna array for heating bladder, ii) EMI-shielded log spiral microstrip receive antenna, iii) high-sensitivity 1.375GHz total power radiometer, iv) power modulation approach to increase urine temperature relative to overlying perfused tissues, and v) invivo porcine experiments characterizing bladder heating and radiometric temperature of aaline filled 30mL balloon "kidney" implanted 3-4cm deep in thorax and varied 2-6°C from core temperature. Results: SAR distributions are presented for two novel antennas designed to heat bladder and monitor deep kidney temperatures radiometrically. We demonstrate the ability to heat 180mL saline in in vivo porcine bladder to 40-44°C while maintaining overlying tissues <38°C using time-modulated square slot antennas coupled to the abdomen with room temperature water pad. Pathologic evaluations confirmed lack of acute thermal damage in pelvic tissues for up to three 20min bladder heat exposures. The radiometer clearly recorded 2-6°C changes of 30mL "kidney" targets at depth in 34°C invivo pig thorax. Conclusion: A 915MHz antenna array can gently warm in vivo pig bladder without toxicity while a 1.375GHz radiometer with log spiral receive antenna detects >=2°C rise in 30mL "urine" located 3-4cm deep in thorax, demonstrating more than sufficient sensitivity to detect Grade 4-5 reflux of warmed urine for non-invasive detection of VUR.

  12. Therapeutic Ultrasound to Non-Invasively Create Intra-Cardiac Communications in an Intact Animal Model

    PubMed Central

    Owens, Gabe E.; Miller, Ryan M.; Ensing, Greg; Ives, Kimberly; Gordon, David; Ludomirsky, Achi; Xu, Zhen

    2010-01-01

    Objective To determine if pulsed cavitational ultrasound therapy (histotripsy) can accurately and safely generate ventricular septal defects (VSDs) through the intact chest of a neonatal animal, with the eventual goal of developing a non-invasive technique of creating intra-cardiac communications in patients with congenital heart disease. Background Histotripsy is an innovative ultrasonic technique that generates demarcated, mechanical tissue fract