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Sample records for improved tumor imaging

  1. The use of image morphing to improve the detection of tumors in emission imaging

    SciTech Connect

    Dykstra, C.; Greer, K.; Jaszczak, R.; Celler, A.

    1999-06-01

    Two of the limitations on the utility of SPECT and planar scintigraphy for the non-invasive detection of carcinoma are the small sizes of many tumors and the possible low contrast between tumor uptake and background. This is particularly true for breast imaging. Use of some form of image processing can improve the visibility of tumors which are at the limit of hardware resolution. Smoothing, by some form of image averaging, either during or post-reconstruction, is widely used to reduce noise and thereby improve the detectability of regions of elevated activity. However, smoothing degrades resolution and, by averaging together closely spaced noise, may make noise look like a valid region of increased uptake. Image morphing by erosion and dilation does not average together image values; it instead selectively removes small features and irregularities from an image without changing the larger features. Application of morphing to emission images has shown that it does not, therefore, degrade resolution and does not always degrade contrast. For these reasons it may be a better method of image processing for noise removal in some images. In this paper the authors present a comparison of the effects of smoothing and morphing using breast and liver studies.

  2. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Yin, Xindao; Shi, Luyao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis; Toumoulin, Christine

    2013-08-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors.

  3. Automatic block-matching registration to improve lung tumor localization during image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Robertson, Scott Patrick

    To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed "blocks", are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy.

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  5. Automatic segmentation of breast tumor in ultrasound image with simplified PCNN and improved fuzzy mutual information

    NASA Astrophysics Data System (ADS)

    Shi, Jun; Xiao, Zhiheng; Zhou, Shichong

    2010-07-01

    Image segmentation is very important in the field of image processing. The pulse coupled neural network (PCNN) has been efficiently applied to image processing, especially for image segmentation. In this study, a simplified PCNN (S-PCNN) model is proposed, the fuzzy mutual information (FMI) is improved as optimization criterion for S-PCNN, and then the S-PCNN and improved FMI (IFMI) based segmentation algorithm is proposed and applied for the segmentation of breast tumor in ultrasound image. To validate the proposed algorithm, a comparative experiment is implemented to segment breast images not only by our proposed algorithm, but also by the improved C-V algorithm, the max-entropy-based PCNN algorithm, the MI-based PCNN algorithm, and the IFMI-based PCNN algorithm. The results show that the breast lesions are well segmented by the proposed algorithm without image preprocessing, with the mean Hausdorff of distance of 5.631+/-0.822, mean average minimum Euclidean distance of 0.554+/-0.049, mean Tanimoto coefficient of 0.961+/-0.019, and mean misclassified error of 0.038+/-0.004. These values of evaluation indices are better than those of other segmentation algorithms. The results indicate that the proposed algorithm has excellent segmentation accuracy and strong robustness against noise, and it has the potential for breast ultrasound computer-aided diagnosis (CAD).

  6. Interrogating Tumor Metabolism and Tumor Microenvironments Using Molecular Positron Emission Tomography Imaging. Theranostic Approaches to Improve Therapeutics

    PubMed Central

    Jacobson, Orit

    2013-01-01

    Positron emission tomography (PET) is a noninvasive molecular imaging technology that is becoming increasingly important for the measurement of physiologic, biochemical, and pharmacological functions at cellular and molecular levels in patients with cancer. Formation, development, and aggressiveness of tumor involve a number of molecular pathways, including intrinsic tumor cell mutations and extrinsic interaction between tumor cells and the microenvironment. Currently, evaluation of these processes is mainly through biopsy, which is invasive and limited to the site of biopsy. Ongoing research on specific target molecules of the tumor and its microenvironment for PET imaging is showing great potential. To date, the use of PET for diagnosing local recurrence and metastatic sites of various cancers and evaluation of treatment response is mainly based on [18F]fluorodeoxyglucose ([18F]FDG), which measures glucose metabolism. However, [18F]FDG is not a target-specific PET tracer and does not give enough insight into tumor biology and/or its vulnerability to potential treatments. Hence, there is an increasing need for the development of selective biologic radiotracers that will yield specific biochemical information and allow for noninvasive molecular imaging. The possibility of cancer-associated targets for imaging will provide the opportunity to use PET for diagnosis and therapy response monitoring (theranostics) and thus personalized medicine. This article will focus on the review of non-[18F]FDG PET tracers for specific tumor biology processes and their preclinical and clinical applications. PMID:24064460

  7. Trial for improvement of visibility of tumor by three digital imaging processing

    NASA Astrophysics Data System (ADS)

    Okada, Kazuhide

    2010-01-01

    To observe the internal of organ clearly, CT/PET and MRI are recently being used. But in order to save demerit toward the high cost and non-real time observation by these machines, diagnostic ultrasound system is remarked. But there are several problems around visibility through ultrasound. Artifact problem are followed by reflection/refraction at the organ borders, lack of directivity of shooting, or reinforcement of wave. In addition, vagueness and darkness are inferior to those for CT/PET or MRI. In order to improve the image resolution along which wave is reflected on tumors by ultrasonic diagnostic equipment, the proposed functions are newly added. First one is duplicated function of two dimensional linear mapping, the second is Differential filter, and the last one is Median filter.

  8. Modern Brain Tumor Imaging

    PubMed Central

    Barajas, Ramon F.; Cha, Soonmee

    2015-01-01

    The imaging and clinical management of patients with brain tumor continue to evolve over time and now heavily rely on physiologic imaging in addition to high-resolution structural imaging. Imaging remains a powerful noninvasive tool to positively impact the management of patients with brain tumor. This article provides an overview of the current state-of-the art clinical brain tumor imaging. In this review, we discuss general magnetic resonance (MR) imaging methods and their application to the diagnosis of, treatment planning and navigation, and disease monitoring in patients with brain tumor. We review the strengths, limitations, and pitfalls of structural imaging, diffusion-weighted imaging techniques, MR spectroscopy, perfusion imaging, positron emission tomography/MR, and functional imaging. Overall this review provides a basis for understudying the role of modern imaging in the care of brain tumor patients. PMID:25977902

  9. Imaging the Tumor Microenvironment

    PubMed Central

    LeBleu, Valerie

    2015-01-01

    The tumor microenvironment is a complex, heterogeneous, and dominant component of solid tumors. Cancer imaging strategies of a subset of characteristics of the tumor microenvironment are under active development and currently used modalities and novel approaches are summarized here. Understanding the dynamic and evolving functions of the tumor microenvironment is critical to accurately inform imaging and clinical care of cancer. Novel insights into distinct roles of the tumor microenvironment in cancer progression urge careful interpretation of imaging data and impel the development of novel modalities. PMID:26049696

  10. Co-registration of ultrasound and frequency-domain photoacoustic radar images and image improvement for tumor detection

    NASA Astrophysics Data System (ADS)

    Dovlo, Edem; Lashkari, Bahman; Choi, Sung soo Sean; Mandelis, Andreas

    2015-03-01

    This paper demonstrates the co-registration of ultrasound (US) and frequency domain photoacoustic radar (FD-PAR) images with significant image improvement from applying image normalization, filtering and amplification techniques. Achieving PA imaging functionality on a commercial Ultrasound instrument could accelerate clinical acceptance and use. Experimental results presented demonstrate live animal testing and show enhancements in signal-to-noise ratio (SNR), contrast and spatial resolution. The co-registered image produced from the US and phase PA images, provides more information than both images independently.

  11. Improvement of therapeutic index for brain tumors with daily image guidance

    PubMed Central

    2013-01-01

    Background Image-guidance maximizes the therapeutic index of brain irradiation by decreasing setup uncertainty. As dose-volume data emerge defining the tolerance of critical normal structures responsible for neuroendocrine function and neurocognition, minimizing clinical target volume (CTV) to planning target volume (PTV) expansion of targets near these structures potentially lessens long-term toxicity. Methods We reviewed the treatment records of 29 patients with brain tumors, with a total of 517 fractions analyzed. The CTV was uniformly expanded by 3 mm to create the PTV for all cases. We determined the effect of patient specific factors (prescribed medications, weight gain, tumor location) and image-guidance technique on setup uncertainty and plotted the mean +/- standard deviation for each factor. ANOVA was used to determine significance between these factors on setup uncertainty. We determined the impact of applying the initial three fraction variation as custom PTV-expansion on dose to normal structures. Results The initial 3 mm margin encompassed 88% of all measured shifts from daily imaging for all fractions. There was no difference (p = n.s.) in average setup uncertainty between CBCT or kV imaging for all patients. Vertical, lateral, longitudinal, and 3D shifts were similar (p = n.s.) between days 1, 2, and 3 imaging and later fractions. Patients prescribed sedatives experienced increased setup uncertainty (p < 0.05), while weight gain, corticosteroid administration, and anti-seizure medication did not associate with increased setup uncertainty. Patients with targets near OAR with individualized margins led to decreased OAR dose. No reductions to targets occurred with individualized PTVs. Conclusions Daily imaging allows application of individualized CTV expansion to reduce dose to OAR responsible for neurocognition, learning, and neuroendocrine function below doses shown to correlate with long-term morbidity. The demonstrated reduction in

  12. Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy

    PubMed Central

    Hoopes, P. Jack; Petryk, Alicia A.; Tate, Jennifer A.; Savellano, Mark S.; Strawbridge, Rendall R.; Giustini, Andrew J.; Stan, Radu V.; Gimi, Barjor; Garwood, Michael

    2014-01-01

    The predicted success of nanoparticle based cancer therapy is due in part to the presence of the inherent leakiness of the tumor vascular barrier, the so called enhanced permeability and retention (EPR) effect. Although the EPR effect is present in varying degrees in many tumors, it has not resulted in the consistent level of nanoparticle-tumor uptake enhancement that was initially predicted. Magnetic/iron oxide nanoparticles (mNPs) have many positive qualities, including their inert/nontoxic nature, the ability to be produced in various sizes, the ability to be activated by a deeply penetrating and nontoxic magnetic field resulting in cell-specific cytotoxic heating, and the ability to be successfully coated with a wide variety of functional coatings. However, at this time, the delivery of adequate numbers of nanoparticles to the tumor site via systemic administration remains challenging. Ionizing radiation, cisplatinum chemotherapy, external static magnetic fields and vascular disrupting agents are being used to modify the tumor environment/vasculature barrier to improve mNP uptake in tumors and subsequently tumor treatment. Preliminary studies suggest use of these modalities, individually, can result in mNP uptake improvements in the 3–10 fold range. Ongoing studies show promise of even greater tumor uptake enhancement when these methods are combined. The level and location of mNP/Fe in blood and normal/tumor tissue is assessed via histopathological methods (confocal, light and electron microscopy, histochemical iron staining, fluorescent labeling, TEM) and ICP-MS. In order to accurately plan and assess mNP-based therapies in clinical patients, a noninvasive and quantitative imaging technique for the assessment of mNP uptake and biodistribution will be necessary. To address this issue, we examined the use of computed tomography (CT), magnetic resonance imaging (MRI), and Sweep Imaging With Fourier Transformation (SWIFT), an MRI technique which provides a

  13. Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy

    NASA Astrophysics Data System (ADS)

    Hoopes, P. Jack; Petryk, Alicia A.; Tate, Jennifer A.; Savellano, Mark S.; Strawbridge, Rendall R.; Giustini, Andrew J.; Stan, Radu V.; Gimi, Barjor; Garwood, Michael

    2013-02-01

    The predicted success of nanoparticle based cancer therapy is due in part to the presence of the inherent leakiness of the tumor vascular barrier, the so called enhanced permeability and retention (EPR) effect. Although the EPR effect is present in varying degrees in many tumors, it has not resulted in the consistent level of nanoparticle-tumor uptake enhancement that was initially predicted. Magnetic/iron oxide nanoparticles (mNPs) have many positive qualities, including their inert/nontoxic nature, the ability to be produced in various sizes, the ability to be activated by a deeply penetrating and nontoxic magnetic field resulting in cell-specific cytotoxic heating, and the ability to be successfully coated with a wide variety of functional coatings. However, at this time, the delivery of adequate numbers of nanoparticles to the tumor site via systemic administration remains challenging. Ionizing radiation, cisplatinum chemotherapy, external static magnetic fields and vascular disrupting agents are being used to modify the tumor environment/vasculature barrier to improve mNP uptake in tumors and subsequently tumor treatment. Preliminary studies suggest use of these modalities, individually, can result in mNP uptake improvements in the 3-10 fold range. Ongoing studies show promise of even greater tumor uptake enhancement when these methods are combined. The level and location of mNP/Fe in blood and normal/tumor tissue is assessed via histopathological methods (confocal, light and electron microscopy, histochemical iron staining, fluorescent labeling, TEM) and ICP-MS. In order to accurately plan and assess mNP-based therapies in clinical patients, a noninvasive and quantitative imaging technique for the assessment of mNP uptake and biodistribution will be necessary. To address this issue, we examined the use of computed tomography (CT), magnetic resonance imaging (MRI), and Sweep Imaging With Fourier Transformation (SWIFT), an MRI technique which provides a

  14. Second antibody clearance of /sup 131/I-labeled anti-carcinoembryonic antigen for improved tumor imaging

    SciTech Connect

    Sharkey, R.M.; Primus, F.J.; Goldenberg, D.M.

    1985-05-01

    The authors have investigated the use of a second antibody (SA) directed against the radiolabeled primary anti-tumor antibody (PA) to enhance the clearance rate of the PA from the circulation and nontarget tissues. Administration of 50 or 250 ..mu..g of anti-goat IgG (SA) hr after the administration of 10 ..mu..g of /sup 131/I-goat anti-carcinoembryonic antigen antibody (PA) to hamsters bearing human colonic tumor xenografts resulted in a 5-fold reduction in the level of circulating PA after 4 hr in comparison to the control group only given /sup 131/I-PA. The percentage of PA in the blood decreased rapidly over 72 hr in animals given 250 ..mu..g of the SA, but at 50 ..mu..g of SA the level of activity in the blood after 24 hr was similar to the control. Tumor accretion was identical after 4 hr, but after 24 hr the animals given 250 ..mu..g of SA had 2-3 fold less PA in the tumor than either the control group or the 50 ..mu..g dose of SA. Tumor/nontumor ratios for all major organs but the spleen improved 6-8 fold within 48 hr after injection of 250 ..mu..g of the SA with tumor/blood ratios as high as 40:1. A SA dose of 50 ..mu..g resulted in a significantly higher tumor/blood ratio after only 4 hr; tumor/nontumor ratios at later times were similar to the control group. Tumors located in the hind legs were visible in all groups by imaging 24 hr after injection of the SA, but only the 250 ..mu..g dose of SA showed a significant reduction in total body activity. These results suggest that the SA approach may be used to reduce the total background radioactivity while maintaining tumor accretion of /sup 131/I-PA to allow for selective tumor imaging.

  15. Brain tumor (image)

    MedlinePlus

    Brain tumors are classified depending on the exact site of the tumor, the type of tissue involved, benign ... tendencies of the tumor, and other factors. Primary brain tumors can arise from the brain cells, the meninges ( ...

  16. CHEMICAL RE-ENGINEERING OF CHLOROTOXIN IMPROVES BIOCONJUGATION PROPERTIES FOR TUMOR IMAGING AND TARGETED THERAPY

    PubMed Central

    Akcan, Muharrem; Stroud, Mark R.; Hansen, Stacey J.; Clark, Richard J.; Daly, Norelle L.; Craik, David J.; Olson, James M.

    2011-01-01

    Bioconjugates composed of chlorotoxin and near infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intra-operative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mixture of mono-, di-, and tri-labeled peptide. Here we report a new chemical entity that bound only a single NIRF molecule. The lysines at positions 15 and 23 were substituted with either Ala or Arg, which resulted in only mono-labeled peptide that was functionally equivalent to native chlorotoxin:Cy5.5. We also analyzed the serum stability and serum half life of cyclized chlorotoxin, which showed an 11 hour serum half life and resulted in a mono-labeled product. Based on these data, we propose to advance a mono-labeled chlorotoxin to human clinical trials. PMID:21210710

  17. Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR{sub 2}* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation

    SciTech Connect

    Baker, Lauren C.J.; Boult, Jessica K.R.; Jamin, Yann; Gilmour, Lesley D.; Walker-Samuel, Simon; Burrell, Jake S.; Ashcroft, Margaret; Howe, Franklyn A.; Griffiths, John R.; Raleigh, James A.; Kogel, Albert J. van der; Robinson, Simon P.

    2013-09-01

    Purpose: To evaluate and histologically qualify carbogen-induced ΔR{sub 2}* as a noninvasive magnetic resonance imaging biomarker of improved tumor oxygenation using a double 2-nitroimidazole hypoxia marker approach. Methods and Materials: Multigradient echo images were acquired from mice bearing GH3 prolactinomas, preadministered with the hypoxia marker CCI-103F, to quantify tumor R{sub 2}* during air breathing. With the mouse remaining positioned within the magnet bore, the gas supply was switched to carbogen (95% O{sub 2}, 5% CO{sub 2}), during which a second hypoxia marker, pimonidazole, was administered via an intraperitoneal line, and an additional set of identical multigradient echo images acquired to quantify any changes in tumor R{sub 2}*. Hypoxic fraction was quantified histologically using immunofluorescence detection of CCI-103F and pimonidazole adduct formation from the same whole tumor section. Carbogen-induced changes in tumor pO{sub 2} were further validated using the Oxylite fiberoptic probe. Results: Carbogen challenge significantly reduced mean tumor R{sub 2}* from 116 ± 13 s{sup −1} to 97 ± 9 s{sup −1} (P<.05). This was associated with a significantly lower pimonidazole adduct area (2.3 ± 1%), compared with CCI-103F (6.3 ± 2%) (P<.05). A significant correlation was observed between ΔR{sub 2}* and Δhypoxic fraction (r=0.55, P<.01). Mean tumor pO{sub 2} during carbogen breathing significantly increased from 6.3 ± 2.2 mm Hg to 36.0 ± 7.5 mm Hg (P<.01). Conclusions: The combined use of intrinsic susceptibility magnetic resonance imaging with a double hypoxia marker approach corroborates carbogen-induced ΔR{sub 2}* as a noninvasive imaging biomarker of increased tumor oxygenation.

  18. Improved tumor imaging and therapy via i.v. IgG–mediated time-sequential modulation of neonatal Fc receptor

    PubMed Central

    Singh Jaggi, Jaspreet; Carrasquillo, Jorge A.; Seshan, Surya V.; Zanzonico, Pat; Henke, Erik; Nagel, Andrew; Schwartz, Jazmin; Beattie, Brad; Kappel, Barry J.; Chattopadhyay, Debjit; Xiao, Jing; Sgouros, George; Larson, Steven M.; Scheinberg, David A.

    2007-01-01

    The long plasma half-life of IgG, while allowing for enhanced tumor uptake of tumor-targeted IgG conjugates, also results in increased background activity and normal-tissue toxicity. Therefore, successful therapeutic uses of conjugated antibodies have been limited to the highly sensitive and readily accessible hematopoietic tumors. We report a therapeutic strategy to beneficially alter the pharmacokinetics of IgG antibodies via pharmacological inhibition of the neonatal Fc receptor (FcRn) using high-dose IgG therapy. IgG-treated mice displayed enhanced blood and whole-body clearance of radioactivity, resulting in better tumor-to-blood image contrast and protection of normal tissue from radiation. Tumor uptake and the resultant therapeutic response was unaltered. Furthermore, we demonstrated the use of this approach for imaging of tumors in humans and discuss its potential applications in cancer imaging and therapy. The ability to reduce the serum persistence of conjugated IgG antibodies after their infusion can enhance their therapeutic index, resulting in improved therapeutic and diagnostic efficacy. PMID:17717602

  19. Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor.

    PubMed

    Jaggi, Jaspreet Singh; Carrasquillo, Jorge A; Seshan, Surya V; Zanzonico, Pat; Henke, Erik; Nagel, Andrew; Schwartz, Jazmin; Beattie, Brad; Kappel, Barry J; Chattopadhyay, Debjit; Xiao, Jing; Sgouros, George; Larson, Steven M; Scheinberg, David A

    2007-09-01

    The long plasma half-life of IgG, while allowing for enhanced tumor uptake of tumor-targeted IgG conjugates, also results in increased background activity and normal-tissue toxicity. Therefore, successful therapeutic uses of conjugated antibodies have been limited to the highly sensitive and readily accessible hematopoietic tumors. We report a therapeutic strategy to beneficially alter the pharmacokinetics of IgG antibodies via pharmacological inhibition of the neonatal Fc receptor (FcRn) using high-dose IgG therapy. IgG-treated mice displayed enhanced blood and whole-body clearance of radioactivity, resulting in better tumor-to-blood image contrast and protection of normal tissue from radiation. Tumor uptake and the resultant therapeutic response was unaltered. Furthermore, we demonstrated the use of this approach for imaging of tumors in humans and discuss its potential applications in cancer imaging and therapy. The ability to reduce the serum persistence of conjugated IgG antibodies after their infusion can enhance their therapeutic index, resulting in improved therapeutic and diagnostic efficacy. PMID:17717602

  20. Imaging Tumor Hypoxia to Advance Radiation Oncology

    PubMed Central

    Lee, Chen-Ting; Boss, Mary-Keara

    2014-01-01

    Abstract Significance: Most solid tumors contain regions of low oxygenation or hypoxia. Tumor hypoxia has been associated with a poor clinical outcome and plays a critical role in tumor radioresistance. Recent Advances: Two main types of hypoxia exist in the tumor microenvironment: chronic and cycling hypoxia. Chronic hypoxia results from the limited diffusion distance of oxygen, and cycling hypoxia primarily results from the variation in microvessel red blood cell flux and temporary disturbances in perfusion. Chronic hypoxia may cause either tumor progression or regressive effects depending on the tumor model. However, there is a general trend toward the development of a more aggressive phenotype after cycling hypoxia. With advanced hypoxia imaging techniques, spatiotemporal characteristics of tumor hypoxia and the changes to the tumor microenvironment can be analyzed. Critical Issues: In this review, we focus on the biological and clinical consequences of chronic and cycling hypoxia on radiation treatment. We also discuss the advanced non-invasive imaging techniques that have been developed to detect and monitor tumor hypoxia in preclinical and clinical studies. Future Directions: A better understanding of the mechanisms of tumor hypoxia with non-invasive imaging will provide a basis for improved radiation therapeutic practices. Antioxid. Redox Signal. 21, 313–337. PMID:24329000

  1. Imaging Tumor Necrosis with Ferumoxytol

    PubMed Central

    Aghighi, Maryam; Golovko, Daniel; Ansari, Celina; Marina, Neyssa M.; Pisani, Laura; Kurlander, Lonnie; Klenk, Christopher; Bhaumik, Srabani; Wendland, Michael; Daldrup-Link, Heike E.

    2015-01-01

    Objective Ultra-small superparamagnetic iron oxide nanoparticles (USPIO) are promising contrast agents for magnetic resonance imaging (MRI). USPIO mediated proton relaxation rate enhancement is strongly dependent on compartmentalization of the agent and can vary depending on their intracellular or extracellular location in the tumor microenvironment. We compared the T1- and T2-enhancement pattern of intracellular and extracellular USPIO in mouse models of cancer and pilot data from patients. A better understanding of these MR signal effects will enable non-invasive characterizations of the composition of the tumor microenvironment. Materials and Methods Six 4T1 and six MMTV-PyMT mammary tumors were grown in mice and imaged with ferumoxytol-enhanced MRI. R1 relaxation rates were calculated for different tumor types and different tumor areas and compared with histology. The transendothelial leakage rate of ferumoxytol was obtained by our measured relaxivity of ferumoxytol and compared between different tumor types, using a t-test. Additionally, 3 patients with malignant sarcomas were imaged with ferumoxytol-enhanced MRI. T1- and T2-enhancement patterns were compared with histopathology in a descriptive manner as a proof of concept for clinical translation of our observations. Results 4T1 tumors showed central areas of high signal on T1 and low signal on T2 weighted MR images, which corresponded to extracellular nanoparticles in a necrotic core on histopathology. MMTV-PyMT tumors showed little change on T1 but decreased signal on T2 weighted images, which correlated to compartmentalized nanoparticles in tumor associated macrophages. Only 4T1 tumors demonstrated significantly increased R1 relaxation rates of the tumor core compared to the tumor periphery (p<0.001). Transendothelial USPIO leakage was significantly higher for 4T1 tumors (3.4±0.9x10-3 mL/min/100cm3) compared to MMTV-PyMT tumors (1.0±0.9x10-3 mL/min/100 cm3). Likewise, ferumoxytol imaging in patients

  2. [Imaging of childhood brain tumors].

    PubMed

    Couanet, D; Adamsbaum, C

    2006-06-01

    Brain tumors represent around a quarter of all solid tumors observed in the pediatric population. Infratentorial tumors are the most frequent, mostly encountered between 4 and 11 years of age. Early imaging is important because initial symptoms can be misinterpreted as statural and pubertal disorders or pseudoabdominal symptoms with apathy and vomiting in infants. Because signal abnormalities on MRI are most often not specific, it is essential to take into account the clinical and topographic characteristics of the lesion to establish an appropriate differential diagnosis. The main patterns of brain tumors observed in pediatrics are presented. Brain metastases are very unusual in children, in contrast to lepto-meningeal metastasis. PMID:16778744

  3. Imaging probe for tumor malignancy

    NASA Astrophysics Data System (ADS)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro

    2009-02-01

    Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

  4. Intraoperative infrared imaging of brain tumors

    PubMed Central

    Gorbach, Alexander M.; Heiss, John D.; Kopylev, Leonid; Oldfield, Edward H.

    2014-01-01

    Object Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear. Methods An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis–astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy. In four cases a cerebral artery was temporarily occluded during the course of the surgery and infrared emissions from the cortex before and after occlusion were compared to establish the relationship of local temperature to regional blood flow. Discrete temperature gradients were associated with surgically verified lesions in all cases. Depending on the type of tumor, the cortex overlying the tumor was either colder or warmer than the surrounding cortex. Spatial reorganization of thermal gradients was observed after tumor resection. Temperature gradients of the cortex in patients with tumors exceeded those measured in the cortex of patients who underwent epilepsy surgery. Conclusions Brain tumors induce changes in cerebral blood flow (CBF) in the cortex, which can be made visible by performing infrared imaging during cranial surgery. A reduction in CBF beyond the tumor margin improves after removal of the lesion. PMID:15599965

  5. Scintigraphic imaging of carcinoid tumors

    SciTech Connect

    Fischer, M.; Kamanabroo, D.

    1985-05-01

    131-1-metaiodobenzylguanidine (131-1-MIBG) is used for scintigraphic localization and treatment of pheochromocytoma and neuroblastoma. Several other tumors, deriving from neuroectoderm (APUD tumors) may also produce catecholamines. 4 patients with surgically proven carcinoid tumors were studied by 131-1-MIBG scintigraphy. Scintigraphic images were performed with a computer assisted gamma camera 2.24, 48 and 72 hours after IV injection of 26 MBq 131-I-MIBG. In one patient single photon emission computed tomography (SPECT) with 185 Mgq 123-I-MIBG was performed additionally. Catecholamines were determined in 24-hours-urinary samples by HPLC. Serotonine was determined in plasma. Catecholamine excretion was normal in all patients, whereas serotonine was elevated in all of them. In 2 of 4 patients slight tracer uptake was observed in some of liver metastases, whereas other metastases in the liver and the primary tumor did not show 131-1-MIBG uptake. In one patient with a carcinoid tumor of the pancreas 131-1-MIBG scintigraphy and SPECT with 123-1-MIBG was positive. In one patient scintigraphy was false negative. MIBG scintigraphy is not only suitable for imaging pheochromocytoma and neuroblastoma, but may also localize carcinoid tumors and their metastases.

  6. 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

  7. Integrin Targeting for Tumor Optical Imaging

    PubMed Central

    Ye, Yunpeng; Chen, Xiaoyuan

    2011-01-01

    Optical imaging has emerged as a powerful modality for studying molecular recognitions and molecular imaging in a noninvasive, sensitive, and real-time way. Some advantages of optical imaging include cost-effectiveness, convenience, and non-ionization safety as well as complementation with other imaging modalities such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Over the past decade, considerable advances have been made in tumor optical imaging by targeting integrin receptors in preclinical studies. This review has emphasized the construction and evaluation of diverse integrin targeting agents for optical imaging of tumors in mouse models. They mainly include some near-infrared fluorescent dye-RGD peptide conjugates, their multivalent analogs, and nanoparticle conjugates for targeting integrin αvβ3. Some compounds targeting other integrin subtypes such as α4β1 and α3 for tumor optical imaging have also been included. Both in vitro and in vivo studies have revealed some promising integrin-targeting optical agents which have further enhanced our understanding of integrin expression and targeting in cancer biology as well as related anticancer drug discovery. Especially, some integrin-targeted multifunctional optical agents including nanoparticle-based optical agents can multiplex optical imaging with other imaging modalities and targeted therapy, serving as an attractive type of theranostics for simultaneous imaging and targeted therapy. Continued efforts to discover and develop novel, innovative integrin-based optical agents with improved targeting specificity and imaging sensitivity hold great promises for improving cancer early detection, diagnosis, and targeted therapy in clinic. PMID:21546996

  8. Radiolabeled Nanoparticles for Multimodality Tumor Imaging

    PubMed Central

    Xing, Yan; Zhao, Jinhua; Conti, Peter S.; Chen, Kai

    2014-01-01

    Each imaging modality has its own unique strengths. Multimodality imaging, taking advantages of strengths from two or more imaging modalities, can provide overall structural, functional, and molecular information, offering the prospect of improved diagnostic and therapeutic monitoring abilities. The devices of molecular imaging with multimodality and multifunction are of great value for cancer diagnosis and treatment, and greatly accelerate the development of radionuclide-based multimodal molecular imaging. Radiolabeled nanoparticles bearing intrinsic properties have gained great interest in multimodality tumor imaging over the past decade. Significant breakthrough has been made toward the development of various radiolabeled nanoparticles, which can be used as novel cancer diagnostic tools in multimodality imaging systems. It is expected that quantitative multimodality imaging with multifunctional radiolabeled nanoparticles will afford accurate and precise assessment of biological signatures in cancer in a real-time manner and thus, pave the path towards personalized cancer medicine. This review addresses advantages and challenges in developing multimodality imaging probes by using different types of nanoparticles, and summarizes the recent advances in the applications of radiolabeled nanoparticles for multimodal imaging of tumor. The key issues involved in the translation of radiolabeled nanoparticles to the clinic are also discussed. PMID:24505237

  9. Intraoperative fluorescent imaging of intracranial tumors: a review.

    PubMed

    Behbahaninia, Milad; Martirosyan, Nikolay L; Georges, Joseph; Udovich, Joshua A; Kalani, M Yashar S; Feuerstein, Burt G; Nakaji, Peter; Spetzler, Robert F; Preul, Mark C

    2013-05-01

    A review of fluorescent imaging for intracranial neoplasms is presented. Complete resection of brain cancer is seldom possible because of the goal to preserve brain tissue and the inability to visualize individual infiltrative tumor cells. Verification of histology and identification of tumor invasion in macroscopically normal-appearing brain tissue determine prognosis after resection of malignant gliomas. Therefore, imaging modalities aim to facilitate intraoperative decision-making. Intraoperative fluorescent imaging techniques have the potential to enable precise histopathologic diagnosis and to detect tumor remnants in the operative field. Macroscopic fluorescence imaging is effective for gross tumor detection. Microscopic imaging techniques enhance the sensitivity of the macroscopic observations and provide real-time histological information. Further development of clinical grade fluorescent agents specifically targeting tumor cells could improve the diagnostic and prognostic yield of intraoperative imaging. PMID:23523009

  10. Image-Guided Tumor Ablation: Emerging Technologies and Future Directions

    PubMed Central

    McWilliams, Justin P.; Lee, Edward W.; Yamamoto, Shota; Loh, Christopher T.; Kee, Stephen T.

    2010-01-01

    As the trend continues toward the decreased invasiveness of medical procedures, image-guided percutaneous ablation has begun to supplant surgery for the local control of small tumors in the liver, kidney, and lung. New ablation technologies, and refinements of existing technologies, will enable treatment of larger and more complex tumors in these and other organs. At the same time, improvements in intraprocedural imaging promise to improve treatment accuracy and reduce complications. In this review, the latest advancements in clinical and experimental ablation technologies will be summarized, and new applications of image-guided tumor ablation will be discussed. PMID:22550370

  11. Tongue Tumor Detection in Medical Hyperspectral Images

    PubMed Central

    Liu, Zhi; Wang, Hongjun; Li, Qingli

    2012-01-01

    A hyperspectral imaging system to measure and analyze the reflectance spectra of the human tongue with high spatial resolution is proposed for tongue tumor detection. To achieve fast and accurate performance for detecting tongue tumors, reflectance data were collected using spectral acousto-optic tunable filters and a spectral adapter, and sparse representation was used for the data analysis algorithm. Based on the tumor image database, a recognition rate of 96.5% was achieved. The experimental results show that hyperspectral imaging for tongue tumor diagnosis, together with the spectroscopic classification method provide a new approach for the noninvasive computer-aided diagnosis of tongue tumors. PMID:22368462

  12. Improving drug delivery to solid tumors: priming the tumor microenvironment.

    PubMed

    Khawar, Iftikhar Ali; Kim, Jung Ho; Kuh, Hyo-Jeong

    2015-03-10

    Malignant transformation and growth of the tumor mass tend to induce changes in the surrounding microenvironment. Abnormality of the tumor microenvironment provides a driving force leading not only to tumor progression, including invasion and metastasis, but also to acquisition of drug resistance, including pharmacokinetic (drug delivery-related) and pharmacodynamic (sensitivity-related) resistance. Drug delivery systems exploiting the enhanced permeability and retention (EPR) effect and active targeting moieties were expected to be able to cope with delivery-related drug resistance. However, recent evidence supports a considerable barrier role of tumors via various mechanisms, which results in imperfect or inefficient EPR and/or targeting effect. The components of the tumor microenvironment such as abnormal tumor vascular system, deregulated composition of the extracellular matrix, and interstitial hypertension (elevated interstitial fluid pressure) collectively or cooperatively hinder the drug distribution, which is prerequisite to the efficacy of nanoparticles and small-molecule drugs used in cancer medicine. Hence, the abnormal tumor microenvironment has recently been suggested to be a promising target for the improvement of drug delivery to improve therapeutic efficacy. Strategies to modulate the abnormal tumor microenvironment, referred to here as "solid tumor priming" (vascular normalization and/or solid stress alleviation leading to improvement in blood perfusion and convective molecular movement), have shown promising results in the enhancement of drug delivery and anticancer efficacy. These strategies may provide a novel avenue for the development of new chemotherapeutics and combination chemotherapeutic regimens as well as reassessment of previously ineffective agents. PMID:25526702

  13. Imaging Tumor Cell Movement In Vivo

    PubMed Central

    Entenberg, David; Kedrin, Dmitriy; Wyckoff, Jeffrey; Sahai, Erik; Condeelis, John; Segall, Jeffrey E.

    2013-01-01

    This unit describes the methods that we have been developing for analyzing tumor cell motility in mouse and rat models of breast cancer metastasis. Rodents are commonly used both to provide a mammalian system for studying human tumor cells (as xenografts in immunocompromised mice) as well as for following the development of tumors from a specific tissue type in transgenic lines. The Basic Protocol in this unit describes the standard methods used for generation of mammary tumors and imaging them. Additional protocols for labeling macrophages, blood vessel imaging, and image analysis are also included. PMID:23456602

  14. Scintigraphic Images of Massive Tumoral Calcinosis.

    PubMed

    Liu, Yiyan

    2016-06-01

    Tumoral calcinosis is a rare family disorder characterized by massive periarticular calcification deposits of the soft tissue. Although radiographic findings of tumoral calcinosis are recognized, there were very scant publications of scintigraphic imaging of the disease. We present here the images of FDG PET/CT and bone scintigraphy in a patient with idiopathic tumoral calcinosis, which are unique in the locations of the lesions and distribution of abnormal uptake. PMID:26909717

  15. Multifunctional nanoparticles for brain tumor imaging and therapy.

    PubMed

    Cheng, Yu; Morshed, Ramin A; Auffinger, Brenda; Tobias, Alex L; Lesniak, Maciej S

    2014-02-01

    Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management. PMID:24060923

  16. "Nanotheranostics" for tumor imaging and targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Zou, Peng

    The magnetic resonance imaging (MRI) technique is a promising tool that improves cancer detection, facilitates diagnosis and monitors therapeutic effects. Superparamagnetic iron oxide nanoparticles (SPIOs) have emerged as MRI contrast agents for tumor imaging and as potential vectors for targeted anti-cancer drug delivery; nevertheless, the application of SPIOs has been hampered due to a lack of specificity to tumor tissues and premature drug release. This project aims at developing multifunctional SPIOs for both cancer imaging and targeted drug delivery via conjugation of tumor specific antibodies with SPIOs. The application of anti-TAG-72 antibodies as tumor targeting modalities was evaluated in cultured colorectal cancer cells and in xenograft models by using fluorescent imaging and positron emission tomography (PET) imaging. It was demonstrated that antibody-labeled SPIOs were superior imaging agents and drug carriers for increased tumor specificity. The regulation and kinetics of intracellular drug release from SPIOs were explored by means of fluorescence imaging. In vitro and in vivo fluorescence resonance energy transfer (FRET) imaging was employed to investigate the mechanisms of premature drug release from nanocarriers. The large volume and high hydrophobicity of cell membranes were found to play an important role in premature drug release. The encapsulation of SPIOs into nanocarriers decreased drug release in a dose-dependent mode. This study provided future opportunities to improve the efficiency of nanocarriers by exploring the mechanism of drug release and disassembly of SPIO-loaded polymeric nanoparticles.

  17. Site specific discrete PEGylation of (124)I-labeled mCC49 Fab' fragments improves tumor MicroPET/CT imaging in mice.

    PubMed

    Ding, Haiming; Carlton, Michelle M; Povoski, Stephen P; Milum, Keisha; Kumar, Krishan; Kothandaraman, Shankaran; Hinkle, George H; Colcher, David; Brody, Rich; Davis, Paul D; Pokora, Alex; Phelps, Mitchell; Martin, Edward W; Tweedle, Michael F

    2013-11-20

    The tumor-associated glycoprotein-72 (TAG-72) antigen is highly overexpressed in various human adenocarcinomas and anti-TAG-72 monoclonal antibodies, and fragments are therefore useful as pharmaceutical targeting vectors. In this study, we investigated the effects of site-specific PEGylation with MW 2-4 kDa discrete, branched PEGylation reagents on mCC49 Fab' (MW 50 kDa) via in vitro TAG72 binding, and in vivo blood clearance kinetics, biodistribution, and mouse tumor microPET/CT imaging. mCC49Fab' (Fab'-NEM) was conjugated at a hinge region cysteine with maleimide-dPEG 12-(dPEG24COOH)3 acid (Mal-dPEG-A), maleimide-dPEG12-(dPEG12COOH)3 acid (Mal-dPEG-B), or maleimide-dPEG12-(m-dPEG24)3 (Mal-dPEG-C), and then radiolabeled with iodine-124 ((124)I) in vitro radioligand binding assays and in vivo studies used TAG-72 expressing LS174T human colon carcinoma cells and xenograft mouse tumors. Conjugation of mCC49Fab' with Mal-dPEG-A (Fab'-A) reduced the binding affinity of the non PEGylated Fab' by 30%; however, in vivo, Fab'-A significantly lengthened the blood retention vs Fab'-NEM (47.5 vs 28.1%/ID at 1 h, 25.1 vs 8.4%/ID at 5 h, p < 0.01), showed excellent tumor to background, better microPET/CT images due to higher tumor accumulation, and increased tumor concentration in excised tissues at 72 h by 130% (5.09 ± 0.83 vs 3.83 ± 1.50%ID/g, p < 0.05). Despite the strong similarity of the three PEGylation reagents, PEGylation with Mal-dPEG-B or -C reduced the in vitro binding affinity of Fab'-NEM by 70%, blood retention, microPET/CT imaging tumor signal intensity, and residual 72 h tumor concentration by 49% (3.83 ± 1.50 vs 1.97 ± 0.29%ID/g, p < 0.05) and 63% (3.83 ± 1.50 vs 1.42 ± 0.35%ID/g, p < 0.05), respectively. We conclude that remarkably subtle changes in the structure of the PEGylation reagent can create significantly altered biologic behavior. Further study is warranted of conjugates of the triple branched, negatively charged Mal-dPEG-A. PMID:24175669

  18. Bladder Tumor Diagnosis—Improved Excretory Cystograms

    PubMed Central

    Amar, Arjan D.

    1967-01-01

    The correct precystoscopic diagnosis of bladder tumor was made in 20 of 23 patients with this disease, among more than 1,000 persons studied by double-dose excretory urography. There was no increase in the incidence of untoward effects. Double-dose excretory urography with delayed bladder films is recommended as the primary urographic procedure in all patients with gross or microscopic hematuria in whom bladder tumor is suspected. ImagesFigure 1.Figure 2.Figure 3. PMID:6044290

  19. Radiation-induced tumor neoantigens: imaging and therapeutic implications

    PubMed Central

    Corso, Christopher D; Ali, Arif N; Diaz, Roberto

    2011-01-01

    Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a number of cellular changes. One way that IR can affect tumor cells is through the development of neoantigens which are new molecules that tumor cells express at the cell membrane following some insult or change to the cell. There have been numerous reports in the literature of changes in both tumor and tumor vasculature cell surface molecule expression following treatment with IR. The usefulness of neoantigens for imaging and therapeutic applications lies in the fact that they are differentially expressed on the surface of irradiated tumor cells to a greater extent than on normal tissues. This differential expression provides a mechanism by which tumor cells can be “marked” by radiation for further targeting. Drug delivery vehicles or imaging agents conjugated to ligands that recognize and interact with the neoantigens can help to improve tumor-specific targeting and reduce systemic toxicity with cancer drugs. This article provides a review of the molecules that have been reported to be expressed on the surface of tumor cells in response to IR either in vivo or in vitro. Additionally, we provide a discussion of some of the methods used in the identification of these antigens and applications for their use in drug delivery and imaging. PMID:21969260

  20. Tumor-stem cells interactions by fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Meleshina, Aleksandra V.; Cherkasova, Elena I.; Sergeeva, Ekaterina; Turchin, Ilya V.; Kiseleva, Ekaterina V.; Dashinimaev, Erdem B.; Shirmanova, Marina V.; Zagaynova, Elena V.

    2013-02-01

    Recently, great deal of interest is investigation the function of the stem cells (SC) in tumors. In this study, we studied «recipient-tumor- fluorescent stem cells » system using the methods of in vivo imaging and laser scanning microscopy (LSM). We used adipose-derived adult stem (ADAS) cells of human lentiviral transfected with the gene of fluorescent protein Turbo FP635. ADAS cells were administrated into nude mice with transplanted tumor HeLa Kyoto (human cervical carcinoma) at different stages of tumor growth (0-8 days) intravenously or into tumor. In vivo imaging was performed on the experimental setup for epi - luminescence bioimaging (IAP RAS, Nizhny Novgorod). The results of the imaging showed localization of fluorophore tagged stem cells in the spleen on day 5-9 after injection. The sensitivity of the technique may be improved by spectral separation autofluorescence and fluorescence of stem cells. We compared the results of in vivo imaging and confocal laser scanning microscopy (LSM 510 META, Carl Zeiss, Germany). Internal organs of the animals and tumor tissue were investigated. It was shown that with i.v. injection of ADAS, bright fluorescent structures with spectral characteristics corresponding to TurboFP635 protein are locally accumulated in the marrow, lungs and tumors of animals. These findings indicate that ADAS cells integrate in the animal body with transplanted tumor and can be identified by fluorescence bioimaging techniques in vivo and ex vivo.

  1. In vivo imaging of tumor vascular endothelial cells

    NASA Astrophysics Data System (ADS)

    Zhao, Dawen; Stafford, Jason H.; Zhou, Heling; Thorpe, Philip E.

    2013-02-01

    Phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, becomes exposed on the outer surface of viable (non-apoptotic) endothelial cells in tumor blood vessels, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we optically imaged exposed PS on tumor vasculature in vivo using PGN635, a novel human monoclonal antibody that targets PS. PGN635 F(ab')2 was labeled with the near infrared (NIR) dye, IRDye 800CW. Human glioma U87 cells or breast cancer MDA-MB-231 cells were implanted subcutaneously or orthotopically into nude mice. When the tumors reached ~5 mm in diameter, 800CW- PGN635 was injected via a tail vein and in vivo dynamic NIR imaging was performed. For U87 gliomas, NIR imaging allowed clear detection of tumors as early as 4 h later, which improved over time to give a maximal tumor/normal ratio (TNR = 2.9 +/- 0.5) 24 h later. Similar results were observed for orthotopic MDA-MB-231 breast tumors. Localization of 800CW-PGN635 to tumors was antigen specific since 800CW-Aurexis, a control probe of irrelevant specificity, did not localize to the tumors, and pre-administration of unlabeled PGN635 blocked the uptake of 800CW-PGN635. Fluorescence microscopy confirmed that 800CW-PGN635 was binding to PS-positive tumor vascular endothelium. Our studies suggest that tumor vasculature can be successfully imaged in vivo to provide sensitive tumor detection.

  2. Imaging radiation response in tumor and normal tissue

    PubMed Central

    Rafat, Marjan; Ali, Rehan; Graves, Edward E

    2015-01-01

    Although X-ray computed tomography (CT) and magnetic resonance imaging (MRI) are the primary imaging modalities used in the clinic to monitor tumor response to radiation therapy, multi-modal molecular imaging may facilitate improved early and specific evaluation of this process. Fast and accurate imaging that can provide both quantitative and biological information is necessary to monitor treatment and ultimately to develop individualized treatment options for patients. A combination of molecular and anatomic information will allow for deeper insight into the mechanisms of tumor response, which will lead to more effective radiation treatments as well as improved anti-cancer drugs. Much progress has been made in nuclear medicine imaging probes and MRI techniques to achieve increased accuracy and the evaluation of relevant biomarkers of radiation response. This review will emphasize promising molecular imaging techniques that monitor various biological processes following radiotherapy, including metabolism, hypoxia, cell proliferation, and angiogenesis. PMID:26269771

  3. A pretargeting system for tumor PET imaging and radioimmunotherapy

    PubMed Central

    Kraeber-Bodéré, Françoise; Rousseau, Caroline; Bodet-Milin, Caroline; Frampas, Eric; Faivre-Chauvet, Alain; Rauscher, Aurore; Sharkey, Robert M.; Goldenberg, David M.; Chatal, Jean-François; Barbet, Jacques

    2015-01-01

    Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed. PMID:25873896

  4. A pretargeting system for tumor PET imaging and radioimmunotherapy.

    PubMed

    Kraeber-Bodéré, Françoise; Rousseau, Caroline; Bodet-Milin, Caroline; Frampas, Eric; Faivre-Chauvet, Alain; Rauscher, Aurore; Sharkey, Robert M; Goldenberg, David M; Chatal, Jean-François; Barbet, Jacques

    2015-01-01

    Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed. PMID:25873896

  5. Pediatric Cerebellar Tumors: Emerging Imaging Techniques and Advances in Understanding of Genetic Features.

    PubMed

    Choudhri, Asim F; Siddiqui, Adeel; Klimo, Paul

    2016-08-01

    Cerebellar tumors are the most common group of solid tumors in children. MR imaging provides an important role in characterization of these lesions, surgical planning, and postsurgical surveillance. Preoperative imaging can help predict the histologic subtype of tumors, which can provide guidance for surgical planning. Beyond histology, pediatric brain tumors are undergoing new classification schemes based on genetic features. Intraoperative MR imaging has emerged as an important tool in the surgical management of pediatric brain tumors. Effective understanding of the imaging features of pediatric cerebellar tumors can benefit communication with neurosurgeons and neuro-oncologists and can improve patient management. PMID:27423803

  6. Imaging Tumor Metabolism Using Positron Emission Tomography

    PubMed Central

    Lewis, David Y.; Soloviev, Dmitry; Brindle, Kevin M.

    2015-01-01

    Positron emission tomography (PET) is an extraordinarily sensitive clinical imaging modality for interrogating tumor metabolism. Radiolabelled PET substrates can be traced at sub-physiological concentrations, allowing non-invasive imaging of metabolism and intra-tumoral heterogeneity in systems ranging from advanced cancer models to cancer patients in the clinic. There are a wide range of novel and more established PET radiotracers, which can be used to investigate various aspects of tumor metabolism, including carbohydrate, amino acid and fatty acid metabolism. In this review we will briefly discuss the more established metabolic tracers and describe recent work on the development of new tracers. Some of the unanswered questions in tumor metabolism will be considered alongside new technical developments, such as combined PET/MRI machines, that could provide new imaging solutions to some of the outstanding diagnostic challenges facing modern cancer medicine. PMID:25815854

  7. 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)

  8. Characterizing intraocular tumors with photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Xu, Guan; Xue, Yafang; Gursel, Zeynep; Slimani, Naziha; Wang, Xueding; Demirci, Hakan

    2016-03-01

    Intraocular tumors are life-threatening conditions. Long-term mortality from uveal melanoma, which accounts for 80% of primary intraocular tumors, could be as high as 25% depending on the size, ciliary body involvement and extraocular extension. The treatments of intraocular tumors include eye-sparing approaches such as radiotherapy and thermotherapy, and the more aggressive enucleation. The accurate diagnosis of intraocular tumors is thereby critical in the management and follow-up of the patients. The diagnosis of intraocular tumors is usually based on clinical examination with acoustic backscattering based ultrasonography. By analyzing the high frequency fluctuations within the ultrasound (US) signals, microarchitecture information inside the tumor can be characterized. However, US cannot interrogate the histochemical components formulating the microarchitecture. One representative example is the inability of US imaging (and other contemporary imaging modalities as well) in differentiating nevoid and melanoma cells as the two types of cells possesses similar acoustic backscattering properties. Combining optical and US imaging, photoacoustic (PA) measurements encode both the microarchitecture and histochemical component information in biological tissue. This study attempts to characterize ocular tumors by analyzing the high frequency signal components in the multispectral PA images. Ex vivo human eye globes with melanoma and retinoblastoma tumors were scanned using less than 6 mJ per square centimeters laser energy with tunable range of 600-1700 nm. A PA-US parallel imaging system with US probes CL15-7 and L22-14 were used to acquire the high frequency PA signals in real time. Preliminary results show that the proposed method can identify uveal melanoma against retinoblastoma tumors.

  9. Functional imaging in tumor-associated lymphatics

    NASA Astrophysics Data System (ADS)

    Kwon, Sunkuk; Sevick-Muraca, Eva M.

    2011-03-01

    The lymphatic system plays an important role in cancer cell dissemination; however whether lymphatic drainage pathways and function change during tumor progression and metastasis remains to be elucidated. In this report, we employed a non-invasive, dynamic near-infrared (NIR) fluorescence imaging technique for functional lymphatic imaging. Indocyanine green (ICG) was intradermally injected into tumor-free mice and mice bearing C6/LacZ rat glioma tumors in the tail or hindlimb. Our imaging data showed abnormal lymphatic drainage pathways and reduction/loss of lymphatic contractile function in mice with lymph node (LN) metastasis, indicating that cancer metastasis to the draining LNs is accompanied by transient changes of the lymphatic architectural network and its function. Therefore, functional lymphatic imaging may provide a role in the clinical staging of cancer.

  10. Imaging tumor metabolism using positron emission tomography.

    PubMed

    Lewis, David Y; Soloviev, Dmitry; Brindle, Kevin M

    2015-01-01

    Positron emission tomography (PET) is an extraordinarily sensitive clinical imaging modality for interrogating tumor metabolism. Radiolabeled PET substrates can be traced at subphysiological concentrations, allowing noninvasive imaging of metabolism and intratumoral heterogeneity in systems ranging from advanced cancer models to patients in the clinic. There are a wide range of novel and more established PET radiotracers, which can be used to investigate various aspects of the tumor, including carbohydrate, amino acid, and fatty acid metabolism. In this review, we briefly discuss the more established metabolic tracers and describe recent work on the development of new tracers. Some of the unanswered questions in tumor metabolism are considered alongside new technical developments, such as combined PET/magnetic resonance imaging scanners, which could provide new imaging solutions to some of the outstanding diagnostic challenges facing modern cancer medicine. PMID:25815854

  11. Nanobubbles for enhanced ultrasound imaging of tumors.

    PubMed

    Yin, Tinghui; Wang, Ping; Zheng, Rongqin; Zheng, Bowen; Cheng, Du; Zhang, Xinling; Shuai, Xintao

    2012-01-01

    The fabrication and initial applications of nanobubbles (NBs) have shown promising results in recent years. A small particle size is a basic requirement for ultrasound contrast-enhanced agents that penetrate tumor blood vessel pores to allow for targeted imaging and therapy. However, the nanoscale size of the particles used has the disadvantage of weakening the imaging ability of clinical diagnostic ultrasound. In this work, we fabricated a lipid NBs contrast-enhanced ultrasound agent and evaluated its passive targeting ability in vivo. The results showed that the NBs were small (436.8 ± 5.7 nm), and in vitro ultrasound imaging suggested that the ultrasonic imaging ability is comparable to that of microbubbles (MBs). In vivo experiments confirmed the ability of NBs to passively target tumor tissues. The NBs remained in the tumor area for a longer period because they exhibited enhanced permeability and retention. Direct evidence was obtained by direct observation of red fluorescence-dyed NBs in tumor tissue using confocal laser scanning microscopy. We have demonstrated the ability to fabricate NBs that can be used for the in vivo contrast-enhanced imaging of tumor tissue and that have potential for drug/gene delivery. PMID:22393289

  12. Gold nanoparticle imaging and radiotherapy of brain tumors in mice

    PubMed Central

    Hainfeld, James F; Smilowitz, Henry M; O'Connor, Michael J; Dilmanian, Farrokh Avraham; Slatkin, Daniel N

    2013-01-01

    Aim To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas. Materials & methods Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays. Results Gold uptake gave a 19:1 tumor-to-normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died. Conclusion Intravenously injected gold nanoparticles cross the blood–tumor barrier, but are largely blocked by the normal blood–brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers. PMID:23265347

  13. Proton MRS imaging in pediatric brain tumors.

    PubMed

    Zarifi, Maria; Tzika, A Aria

    2016-06-01

    Magnetic resonance (MR) techniques offer a noninvasive, non-irradiating yet sensitive approach to diagnosing and monitoring pediatric brain tumors. Proton MR spectroscopy (MRS), as an adjunct to MRI, is being more widely applied to monitor the metabolic aspects of brain cancer. In vivo MRS biomarkers represent a promising advance and may influence treatment choice at both initial diagnosis and follow-up, given the inherent difficulties of sequential biopsies to monitor therapeutic response. When combined with anatomical or other types of imaging, MRS provides unique information regarding biochemistry in inoperable brain tumors and can complement neuropathological data, guide biopsies and enhance insight into therapeutic options. The combination of noninvasively acquired prognostic information and the high-resolution anatomical imaging provided by conventional MRI is expected to surpass molecular analysis and DNA microarray gene profiling, both of which, although promising, depend on invasive biopsy. This review focuses on recent data in the field of MRS in children with brain tumors. PMID:27233788

  14. Markerless tumor tracking using short kilovoltage imaging arcs for lung image-guided radiotherapy

    NASA Astrophysics Data System (ADS)

    Shieh, Chun-Chien; Keall, Paul J.; Kuncic, Zdenka; Huang, Chen-Yu; Feain, Ilana

    2015-12-01

    The ability to monitor tumor motion without implanted markers is clinically advantageous for lung image-guided radiotherapy (IGRT). Existing markerless tracking methods often suffer from overlapping structures and low visibility of tumors on kV projection images. We introduce the short arc tumor tracking (SATT) method to overcome these issues. The proposed method utilizes multiple kV projection images selected from a nine-degree imaging arc to improve tumor localization, and respiratory-correlated 4D cone-beam CT (CBCT) prior knowledge to minimize the effects of overlapping anatomies. The 3D tumor position is solved as an optimization problem with prior knowledge incorporated via regularization. We retrospectively validated SATT on 11 clinical scans from four patients with central tumors. These patients represent challenging scenarios for markerless tumor tracking due to the inferior adjacent contrast. The 3D trajectories of implanted fiducial markers were used as the ground truth for tracking accuracy evaluation. In all cases, the tumors were successfully tracked at all gantry angles. Compared to standard pre-treatment CBCT guidance alone, trajectory errors were significantly smaller with tracking in all cases, and the improvements were the most prominent in the superior-inferior direction. The mean 3D tracking error ranged from 2.2-9.9 mm, which was 0.4-2.6 mm smaller compared to pre-treatment CBCT. In conclusion, we were able to directly track tumors with inferior visibility on kV projection images using SATT. Tumor localization accuracies are significantly better with tracking compared to the current standard of care of lung IGRT. Future work involves the prospective evaluation and clinical implementation of SATT.

  15. Protein-based tumor molecular imaging probes

    PubMed Central

    Lin, Xin; Xie, Jin

    2013-01-01

    Molecular imaging is an emerging discipline which plays critical roles in diagnosis and therapeutics. It visualizes and quantifies markers that are aberrantly expressed during the disease origin and development. Protein molecules remain to be one major class of imaging probes, and the option has been widely diversified due to the recent advances in protein engineering techniques. Antibodies are part of the immunosystem which interact with target antigens with high specificity and affinity. They have long been investigated as imaging probes and were coupled with imaging motifs such as radioisotopes for that purpose. However, the relatively large size of antibodies leads to a half-life that is too long for common imaging purposes. Besides, it may also cause a poor tissue penetration rate and thus compromise some medical applications. It is under this context that various engineered protein probes, essentially antibody fragments, protein scaffolds, and natural ligands have been developed. Compared to intact antibodies, they possess more compact size, shorter clearance time, and better tumor penetration. One major challenge of using protein probes in molecular imaging is the affected biological activity resulted from random labeling. Site-specific modification, however, allows conjugation happening in a stoichiometric fashion with little perturbation of protein activity. The present review will discuss protein-based probes with focus on their application and related site-specific conjugation strategies in tumor imaging. PMID:20232092

  16. Optical imaging of tumor hypoxia dynamics

    NASA Astrophysics Data System (ADS)

    Palmer, Gregory M.; Fontanella, Andrew N.; Zhang, Guoqing; Hanna, Gabi; Fraser, Cassandra L.; Dewhirst, Mark W.

    2010-11-01

    The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent/phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique.

  17. Phyllodes tumor: diagnostic imaging and histopathology findings.

    PubMed

    Venter, Alina Cristiana; Roşca, Elena; Daina, Lucia Georgeta; Muţiu, Gabriela; Pirte, Adriana Nicoleta; Rahotă, Daniela

    2015-01-01

    Phyllodes tumors are rare breast tumors, accounting for less than 1% of all primary tumors of the breast. Histologically, phyllodes tumors can be divided into benign (60%), borderline (20%) and malignant (20%). The mammography examination was performed by means of a digital mammography system Giotto 3D Images; the ultrasound examination was performed through a GE Logiq P6 device and histological confirmation was possible after surgery or following the histological biopsy. We grouped the nine patients who presented clinically palpable nodules into two groups, namely: the six patients presenting histological benign results into Group I, and Group II where we included those with borderline and malignant histological results. Mammography performed in 77.7% revealed a well-circumscribed round or oval opacity or with contour lobules. Ultrasound examination was performed in all patients. Mammography and ultrasound have limitation in differentiating between benign lesion and phyllodes tumor. In the nine analyzed cases, mammographic and ultrasound examinations did not allow the differentiation into the three groups of phyllodes tumor. Histopathological examination is considered the golden standard for their diagnosis. Correlations between mammographic and microscopic aspects were inconclusive for determining the degree of differentiation, ultrasound changes could be correlated with the histopathological aspects. PMID:26743286

  18. Tumor imaging and therapy using radiolabeled somatostatin analogues.

    PubMed

    de Jong, Marion; Breeman, Wout A P; Kwekkeboom, Dik J; Valkema, Roelf; Krenning, Eric P

    2009-07-21

    theranostics could greatly advance the development of personalized treatments. Apart from patient selection for radionuclide therapy, other imaging applications of targeted radiopeptides include localization of primary tumors, detection of metastatic disease (staging/restaging), dosimetry (prediction of response and radiotoxicity), monitoring effects of surgery, radio(nuclide)therapy or chemotherapy, and detection of progression of disease or relapse (follow up). For further evaluation of tumor receptor expression and to increase the value of cancer targeting using radiopeptides, researchers have introduced and evaluated different radiolabeled analogues of other peptide families, such as cholecystokinin (CCK), gastrin, bombesin, substance P, vasoactive intestinal peptide (VIP), and neuropeptide (NP)-Y analogues. We expect improvements in the development of new peptide analogues: such advances could reduce side effects and allow for the use of combination therapy (for example, combining radiopeptide analogues with chemotherapeutics). PMID:19445476

  19. Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes.

    PubMed

    Ruggiero, Alessandro; Villa, Carlos H; Holland, Jason P; Sprinkle, Shanna R; May, Chad; Lewis, Jason S; Scheinberg, David A; McDevitt, Michael R

    2010-01-01

    Single wall carbon nanotube (SWCNT) constructs were covalently appended with radiometal-ion chelates (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA] or desferrioxamine B [DFO]) and the tumor neovascular-targeting antibody E4G10. The E4G10 antibody specifically targeted the monomeric vascular endothelial-cadherin (VE-cad) epitope expressed in the tumor angiogenic vessels. The construct specific activity and blood compartment clearance kinetics were significantly improved relative to corresponding antibodyalone constructs. We performed targeted radioimmunotherapy with a SWCNT-([(225)Ac]DOTA) (E4G10) construct directed at the tumor vasculature in a murine xenograft model of human colon adenocarcinoma (LS174T). The specific construct reduced tumor volume and improved median survival relative to controls. We also performed positron emission tomographic (PET) radioimmunoimaging of the tumor vessels with a SWCNT-([(89)Zr]DFO)(E4G10) construct in the same murine LS174T xenograft model and compared the results to appropriate controls. Dynamic and longitudinal PET imaging of LS174T tumor-bearing mice demonstrated rapid blood clearance (<1 hour) and specific tumor accumulation of the specific construct. Incorporation of the SWCNT scaffold into the construct design permitted us to amplify the specific activity to improve the signal-to-noise ratio without detrimentally impacting the immunoreactivity of the targeting antibody moiety. Furthermore, we were able to exploit the SWCNT pharmacokinetic (PK) profile to favorably alter the blood clearance and provide an advantage for rapid imaging. Near-infrared three-dimensional fluorescent-mediated tomography was used to image the LS174T tumor model, collect antibody-alone PK data, and calculate the number of copies of VE-cad epitope per cell. All of these studies were performed as a single administration of construct and were found to be safe and well tolerated by the murine model. These data have implications that

  20. Simulation of brain tumor resection in image-guided neurosurgery

    NASA Astrophysics Data System (ADS)

    Fan, Xiaoyao; Ji, Songbai; Fontaine, Kathryn; Hartov, Alex; Roberts, David; Paulsen, Keith

    2011-03-01

    Preoperative magnetic resonance images are typically used for neuronavigation in image-guided neurosurgery. However, intraoperative brain deformation (e.g., as a result of gravitation, loss of cerebrospinal fluid, retraction, resection, etc.) significantly degrades the accuracy in image guidance, and must be compensated for in order to maintain sufficient accuracy for navigation. Biomechanical finite element models are effective techniques that assimilate intraoperative data and compute whole-brain deformation from which to generate model-updated MR images (uMR) to improve accuracy in intraoperative guidance. To date, most studies have focused on early surgical stages (i.e., after craniotomy and durotomy), whereas simulation of more complex events at later surgical stages has remained to be a challenge using biomechanical models. We have developed a method to simulate partial or complete tumor resection that incorporates intraoperative volumetric ultrasound (US) and stereovision (SV), and the resulting whole-brain deformation was used to generate uMR. The 3D ultrasound and stereovision systems are complimentary to each other because they capture features deeper in the brain beneath the craniotomy and at the exposed cortical surface, respectively. In this paper, we illustrate the application of the proposed method to simulate brain tumor resection at three temporally distinct surgical stages throughout a clinical surgery case using sparse displacement data obtained from both the US and SV systems. We demonstrate that our technique is feasible to produce uMR that agrees well with intraoperative US and SV images after dural opening, after partial tumor resection, and after complete tumor resection. Currently, the computational cost to simulate tumor resection can be up to 30 min because of the need for re-meshing and the trial-and-error approach to refine the amount of tissue resection. However, this approach introduces minimal interruption to the surgical workflow

  1. Neuromorphometry of primary brain tumors by magnetic resonance imaging

    PubMed Central

    Hevia-Montiel, Nidiyare; Rodriguez-Perez, Pedro I.; Lamothe-Molina, Paul J.; Arellano-Reynoso, Alfonso; Bribiesca, Ernesto; Alegria-Loyola, Marco A.

    2015-01-01

    Abstract. Magnetic resonance imaging is a technique for the diagnosis and classification of brain tumors. Discrete compactness is a morphological feature of two-dimensional and three-dimensional objects. This measure determines the compactness of a discretized object depending on the sum of the areas of the connected voxels and has been used for understanding the morphology of nonbrain tumors. We hypothesized that regarding brain tumors, we may improve the malignancy grade classification. We analyzed the values in 20 patients with different subtypes of primary brain tumors: astrocytoma, oligodendroglioma, and glioblastoma multiforme subdivided into the contrast-enhanced and the necrotic tumor regions. The preliminary results show an inverse relationship between the compactness value and the malignancy grade of gliomas. Astrocytomas exhibit a mean of 973±14, whereas oligodendrogliomas exhibit a mean of 942±21. In contrast, the contrast-enhanced region of the glioblastoma presented a mean of 919±43, and the necrotic region presented a mean of 869±66. However, the volume and area of the enclosing surface did not show a relationship with the malignancy grade of the gliomas. Discrete compactness appears to be a stable characteristic between primary brain tumors of different malignancy grades, because similar values were obtained from different patients with the same type of tumor. PMID:26158107

  2. Harmonic Motion Imaging (HMI) for Tumor Imaging and Treatment Monitoring

    PubMed Central

    Maleke, Caroline; Vappou, Jonathan

    2014-01-01

    Palpation is an established screening procedure for the detection of several superficial cancers including breast, thyroid, prostate, and liver tumors through both self and clinical examinations. This is because solid masses typically have distinct stiffnesses compared to the surrounding normal tissue. In this paper, the application of Harmonic Motion Imaging (HMI) for tumor detection based on its stiffness as well as its relevance in thermal treatment is reviewed. HMI uses a focused ultrasound (FUS) beam to generate an oscillatory acoustic radiation force for an internal, non-contact palpation to internally estimate relative tissue hardness. HMI studies have dealt with the measurement of the tissue dynamic motion in response to an oscillatory acoustic force at the same frequency, and have been shown feasible in simulations, phantoms, ex vivo human and bovine tissues as well as animals in vivo. Using an FUS beam, HMI can also be used in an ideal integration setting with thermal ablation using high-intensity focused ultrasound (HIFU), which also leads to an alteration in the tumor stiffness. In this paper, a short review of HMI is provided that encompasses the findings in all the aforementioned areas. The findings presented herein demonstrate that the HMI displacement can accurately depict the underlying tissue stiffness, and the HMI image of the relative stiffness could accurately detect and characterize the tumor or thermal lesion based on its distinct properties. HMI may thus constitute a non-ionizing, cost-efficient and reliable complementary method for noninvasive tumor detection, localization, diagnosis and treatment monitoring. PMID:25364321

  3. Imaging features of primary tumors of the spine: A pictorial essay

    PubMed Central

    Patnaik, Sujata; Jyotsnarani, Y; Uppin, Shantiveer G; Susarla, Rammurti

    2016-01-01

    Primary tumors of spine are rare accounting for less than 5% of new bone tumors diagnosed every year. These tumors may exhibit characteristic imaging features that can help in early diagnosis and improved prognosis. Plasmacytoma/multiple myeloma and lymphoproliferative tumors are the most common malignant primary spinal tumors. Hemangioma is the most common benign tumor of the spine. Computed tomography is useful to assess tumor matrix and osseous change. Magnetic resonance is useful to study associated soft tissue extension, marrow infiltration, and intraspinal extension. Confusing one tumor with the other based on only imaging findings is not uncommon. However, radiologic manifestations of these tumors need to be correlated with the age, sex, location, and presentation to arrive at a close clinical diagnosis. PMID:27413280

  4. Exploiting the tumor microenvironment for theranostic imaging

    PubMed Central

    Stasinopoulos, Ioannis; Penet, Marie-France; Chen, Zhihang; Kakkad, Samata; Glunde, Kristine; Bhujwalla, Zaver M.

    2011-01-01

    The integration of chemistry and molecular biology with imaging is providing some of the most exciting opportunities in the treatment of cancer. The field of theranostic imaging, where diagnosis is combined with therapy, is particularly suitable for a disease as complex as cancer, especially now that genomic and proteomic profiling can provide an extensive `fingerprint' of each tumor. Using this information, theranostic agents can be shaped for personalized treatment to target specific compartments, such as the tumor microenvironment (TME), whilst minimizing damage to normal tissue. These theranostic agents can also be used to target multiple pathways or networks by incorporating multiple small interfering RNAs (siRNAs) within a single agent. A decade ago genetic alterations were the primary focus in cancer research. Now it is apparent that the tumor physiological microenvironment, interactions between cancer cells and stromal cells, such as endothelial cells, fibroblasts and macrophages, the extracellular matrix (ECM), and a host of secreted factors and cytokines, influence progression to metastatic disease, aggressiveness and the response of the disease to treatment. In this review, we outline some of the characteristics of the TME, describe the theranostic agents currently available to target the TME and discuss the unique opportunities the TME provides for the design of novel theranostic agents for cancer therapy. PMID:21793072

  5. The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS).

    PubMed

    Menze, Bjoern H; Jakab, Andras; Bauer, Stefan; Kalpathy-Cramer, Jayashree; Farahani, Keyvan; Kirby, Justin; Burren, Yuliya; Porz, Nicole; Slotboom, Johannes; Wiest, Roland; Lanczi, Levente; Gerstner, Elizabeth; Weber, Marc-André; Arbel, Tal; Avants, Brian B; Ayache, Nicholas; Buendia, Patricia; Collins, D Louis; Cordier, Nicolas; Corso, Jason J; Criminisi, Antonio; Das, Tilak; Delingette, Hervé; Demiralp, Çağatay; Durst, Christopher R; Dojat, Michel; Doyle, Senan; Festa, Joana; Forbes, Florence; Geremia, Ezequiel; Glocker, Ben; Golland, Polina; Guo, Xiaotao; Hamamci, Andac; Iftekharuddin, Khan M; Jena, Raj; John, Nigel M; Konukoglu, Ender; Lashkari, Danial; Mariz, José Antonió; Meier, Raphael; Pereira, Sérgio; Precup, Doina; Price, Stephen J; Raviv, Tammy Riklin; Reza, Syed M S; Ryan, Michael; Sarikaya, Duygu; Schwartz, Lawrence; Shin, Hoo-Chang; Shotton, Jamie; Silva, Carlos A; Sousa, Nuno; Subbanna, Nagesh K; Szekely, Gabor; Taylor, Thomas J; Thomas, Owen M; Tustison, Nicholas J; Unal, Gozde; Vasseur, Flor; Wintermark, Max; Ye, Dong Hye; Zhao, Liang; Zhao, Binsheng; Zikic, Darko; Prastawa, Marcel; Reyes, Mauricio; Van Leemput, Koen

    2015-10-01

    In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource. PMID:25494501

  6. Testicular tumors: oncologic imaging and diagnosis

    SciTech Connect

    Heiken, J.P.; Balfe, D.M.; McClennan, B.L.

    1984-02-01

    The extreme radiosensitivity of testicular seminomas plus recent advances in chemotherapy for nonseminomatous tumors and for advanced seminomas have made long term survival possible in the large majority of patients with testis cancer. Since choice of therapy is determined by tumor histology and extent of disease, accurate clinical staging is critical. Computed tomography (CT) of the abdomen and chest is the imaging procedure of choice for staging testis cancer. Clinical staging accuracy of 80 to 90% can be achieved using CT in combination with radio-immunoassays for ..beta..-HCG and AFP. Ultrasonography (US), while less sensitive and specific than CT for determining nodal status, may be useful in thin patients with sparse retroperitoneal fat. Lymphangiography should be reserved for Stage I patients in whom elective treatment of the retroperitoneum is not planned. Follow-up should include serial radioimmunoassays for serum AFP and ..beta..-HCG and periodic CT examinations of the abdomen and chest. In addition, nuclear magnetic resonance (NMR) imaging and radionuclide imaging following injection of radioactively labelled antibodies to AFP and ..beta..-HCG are new techniques which offer great promise for the future.

  7. Phthalocyanine-labeled LDL for tumor imaging and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Li, Hui; Marotta, Diane; Kim, Soungkyoo; Chance, Britton; Glickson, Jerry D.; Busch, Theresa M.; Zheng, Gang

    2005-01-01

    Current limitation of both near-infrared (NIR) tumor imaging and photodynamic therapy (PDT) is their lack of sufficient tumor-to-tissue contrast due to the relatively non-specific nature of delivering dye to the tumor, which has led to false negatives for NIR imaging and inadequate therapeutic ratio for PDT. Hence, agents targeting "cancer signatures", i.e. molecules that accumulate selectively in cancer cells, are particular attractive. One of these signatures is low-density-lipoprotein receptor (LDLR), which is overexpressed in many tumors. We have developed pyropheophorbide cholesterol oleate reconstituted LDL as a LDLR-targeting photosensitizer (PS) and demonstrated its LDLR-mediated uptake in vitro and in vivo. To improve the labeling efficiency for achieving high probe/protein ratio, tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, (tBu)4SiPcBOA, was designed and synthesized. This compound was designed to 1) prevent the PS aggregation; 2) improve the PS solubility in non-polar solvent; and 3) maximize the PS binding to LDL phospholipid monolayer. Using this novel strategy, (tBu)4SiPcBOA was reconstituted into LDL (r-SiPcBOA-LDL) with a very high payload (500:1 molar ratio). In addition, (tBu)4SiPcBOA reconstituted acetylated LDL (r-SiPcBOA)-AcLDL with similar payload was also prepared. Since Ac-LDL cannot bind to LDLR, (r-SiPcBOA)-AcLDL can serve as the negative control to evaluate LDLR targeting specificity. For biological evaluation of these new agents, confocal microscopy and in vitro PDT protocols were performed using LDLR-overexpressing human hepatoblastoma G2 (HepG2) tumor model. These studies suggest that LDL serves as a delivery vehicle to bring large amount of the NIR/PDT agents selectively to tumor cells overexpressing LDLR.

  8. SU-E-J-29: Audiovisual Biofeedback Improves Tumor Motion Consistency for Lung Cancer Patients

    SciTech Connect

    Lee, D; Pollock, S; Makhija, K; Keall, P; Greer, P; Arm, J; Hunter, P; Kim, T

    2014-06-01

    Purpose: To investigate whether the breathing-guidance system: audiovisual (AV) biofeedback improves tumor motion consistency for lung cancer patients. This will minimize respiratory-induced tumor motion variations across cancer imaging and radiotherapy procedues. This is the first study to investigate the impact of respiratory guidance on tumor motion. Methods: Tumor motion consistency was investigated with five lung cancer patients (age: 55 to 64), who underwent a training session to get familiarized with AV biofeedback, followed by two MRI sessions across different dates (pre and mid treatment). During the training session in a CT room, two patient specific breathing patterns were obtained before (Breathing-Pattern-1) and after (Breathing-Pattern-2) training with AV biofeedback. In each MRI session, four MRI scans were performed to obtain 2D coronal and sagittal image datasets in free breathing (FB), and with AV biofeedback utilizing Breathing-Pattern-2. Image pixel values of 2D images after the normalization of 2D images per dataset and Gaussian filter per image were used to extract tumor motion using image pixel values. The tumor motion consistency of the superior-inferior (SI) direction was evaluated in terms of an average tumor motion range and period. Results: Audiovisual biofeedback improved tumor motion consistency by 60% (p value = 0.019) from 1.0±0.6 mm (FB) to 0.4±0.4 mm (AV) in SI motion range, and by 86% (p value < 0.001) from 0.7±0.6 s (FB) to 0.1±0.2 s (AV) in period. Conclusion: This study demonstrated that audiovisual biofeedback improves both breathing pattern and tumor motion consistency for lung cancer patients. These results suggest that AV biofeedback has the potential for facilitating reproducible tumor motion towards achieving more accurate medical imaging and radiation therapy procedures.

  9. Viral Nanoparticles for In vivo Tumor Imaging

    PubMed Central

    Wen, Amy M.; Lee, Karin L.; Yildiz, Ibrahim; Bruckman, Michael A.; Shukla, Sourabh; Steinmetz, Nicole F.

    2012-01-01

    proteinaceous nanoparticles while enhancing their pharmacokinetics 8,11. We demonstrate tumor homing of PEGylated VNPs using a mouse xenograft tumor model. A combination of fluorescence imaging of tissues ex vivo using Maestro Imaging System, fluorescence quantification in homogenized tissues, and confocal microscopy is used to study biodistribution. VNPs are cleared via the reticuloendothelial system (RES); tumor homing is achieved passively via the enhanced permeability and retention (EPR) effect12. The VNP nanotechnology is a powerful plug-and-play technology to image and treat sites of disease in vivo. We are further developing VNPs to carry drug cargos and clinically-relevant imaging moieties, as well as tissue-specific ligands to target molecular receptors overexpressed in cancer and cardiovascular disease. PMID:23183850

  10. Improvement of CAT scanned images

    NASA Technical Reports Server (NTRS)

    Roberts, E., Jr.

    1980-01-01

    Digital enhancement procedure improves definition of images. Tomogram is generated from large number of X-ray beams. Beams are collimated and small in diameter. Scanning device passes beams sequentially through human subject at many different angles. Battery of transducers opposite subject senses attenuated signals. Signals are transmitted to computer where they are used in construction of image on transverse plane through body.

  11. Imaging appearance of bone tumors of the maxillofacial region

    PubMed Central

    Razek, Ahmed Abdel Khalek Abdel

    2011-01-01

    This paper reviews the imaging appearance of benign and malignant bone tumors of the maxillofacial region. A benign bone tumor commonly appears as a well circumscribed lesion. The matrix of the tumor may be calcified or sclerotic. Malignancies often display aggressive characteristics such as cortical breakthrough, bone destruction, a permeative pattern and associated soft-tissue masses. Computed tomography scan is an excellent imaging modality for accurate localization of the lesion, characterization of the tumor matrix and detection of associated osseous changes such as bone remodeling, destruction or periosteal reaction. Magnetic resonance imaging is of limited value in the evaluation of maxillofacial bone tumors. PMID:21666818

  12. Imaging findings of various talus bone tumors-clinico-radiologic features of talus bone tumors.

    PubMed

    Jeon, Ji Young; Chung, Hye Won; Kwon, Jong Won; Hong, Sung Hwan; Lee, Guen Young; Ryu, Kyung Nam

    2016-01-01

    Osseous neoplasms of the foot are uncommon, accounting for only 3.3% of all primary bone tumors. Bone tumors of the talus are even rarer, and there are not many publications that comprehensively evaluate the imaging findings of talus tumors. The purpose of this article is to review the benign and malignant bone tumors affecting this uncommon site and to describe the clinical and radiologic features of each tumor. PMID:27317211

  13. Functional-anatomical image fusion in neuroendocrine tumors.

    PubMed

    Schillaci, Orazio

    2004-02-01

    Nuclear medicine provides physiologic and functional data for normal and pathologic organs but often the clear definition of the sites of radiotracers' uptake are difficult. Radiological methods are able to identify structural changes in a detailed way, but do not give precise information on function of organs or pathologic lesions. The registration and fusion of nuclear medicine studies with structural information obtained by radiological exams allows the precise correlation of functional and anatomical data. Software-based fusion of independently performed nuclear medicine and morphologic studies is uncertain of success and the alignment procedures are labor intensive. Recently, a new imaging device combining a dual-head, variable angle gamma camera with a low-dose x-ray tube has been introduced; the acquired single-photon emission computed tomography (SPECT) and x-ray computed tomography (CT) images are coregistered by means of the hardware in the same session. This new technology can be particularly useful when applied to scintigraphic procedures in neuroendocrine tumors. In-111 pentetreotide and radiolabeled MIBG play an important role in the study of patients with these tumors; the addition of anatomical maps provides a precise localization of SPECT findings and allows the exclusion of disease in sites of physiologic tracer uptake. SPECT/CT fused images are able to provide additional information that improves the accuracy of SPECT interpretation and leads to changes in therapeutic options, so enhancing the clinical role of nuclear medicine in evaluating patients with neuroendocrine tumors. PMID:15068621

  14. Reproducibility of radiomics for deciphering tumor phenotype with imaging

    PubMed Central

    Zhao, Binsheng; Tan, Yongqiang; Tsai, Wei-Yann; Qi, Jing; Xie, Chuanmiao; Lu, Lin; Schwartz, Lawrence H.

    2016-01-01

    Radiomics (radiogenomics) characterizes tumor phenotypes based on quantitative image features derived from routine radiologic imaging to improve cancer diagnosis, prognosis, prediction and response to therapy. Although radiomic features must be reproducible to qualify as biomarkers for clinical care, little is known about how routine imaging acquisition techniques/parameters affect reproducibility. To begin to fill this knowledge gap, we assessed the reproducibility of a comprehensive, commonly-used set of radiomic features using a unique, same-day repeat computed tomography data set from lung cancer patients. Each scan was reconstructed at 6 imaging settings, varying slice thicknesses (1.25 mm, 2.5 mm and 5 mm) and reconstruction algorithms (sharp, smooth). Reproducibility was assessed using the repeat scans reconstructed at identical imaging setting (6 settings in total). In separate analyses, we explored differences in radiomic features due to different imaging parameters by assessing the agreement of these radiomic features extracted from the repeat scans reconstructed at the same slice thickness but different algorithms (3 settings in total). Our data suggest that radiomic features are reproducible over a wide range of imaging settings. However, smooth and sharp reconstruction algorithms should not be used interchangeably. These findings will raise awareness of the importance of properly setting imaging acquisition parameters in radiomics/radiogenomics research. PMID:27009765

  15. Magnetic Resonance Imaging of Pituitary Tumors.

    PubMed

    Bonneville, Jean-François

    2016-01-01

    Magnetic Resonance Imaging (MRI) is currently considered a major keystone of the diagnosis of diseases of the hypothalamic-hypophyseal region. However, the relatively small size of the pituitary gland, its location deep at the skull base and the numerous physiological variants present in this area impede the precise assessment of the anatomical structures and, particularly, of the pituitary gland itself. The diagnosis of the often tiny lesions of this region--such as pituitary microadenomas--is then difficult if the MRI technology is not optimized and if potential artifacts and traps are not recognized. Advanced MRI technology can not only depict small lesions with greater reliability, but also help in the differential diagnosis of large tumors. In these, defining the presence or absence of invasion is a particularly important task. This review describes and illustrates the radiological diagnosis of the different tumors of the sellar region, from the common prolactinomas, nonfunctioning adenomas and Rathke's cleft cysts, to the less frequent and more difficult to detect corticotroph pituitary adenomas in Cushing's disease, and other neoplastic and nonneoplastic entities. Finally, some hints are given to facilitate the differential diagnosis of sellar lesions. PMID:27003878

  16. LCP nanoparticle for tumor and lymph node metastasis imaging

    NASA Astrophysics Data System (ADS)

    Tseng, Yu-Cheng

    A lipid/calcium/phosphate (LCP) nanoparticle formulation (particle diameter ˜25 nm) has previously been developed to delivery siRNA with superior efficiency. In this work, 111In was formulated into LCP nanoparticles to form 111In-LCP for SPECT/CT imaging. With necessary modifications and improvements of the LCP core-washing and surface-coating methods, 111In-LCP grafted with polyethylene glycol exhibited reduced uptake by the mononuclear phagocytic system. SPECT/CT imaging supported performed biodistribution studies, showing clear tumor images with accumulation of 8% or higher injected dose per gram tissue (ID/g) in subcutaneous, human-H460, lung-cancer xenograft and mouse-4T1, breast cancer metastasis models. Both the liver and the spleen accumulated ˜20% ID/g. Accumulation in the tumor was limited by the enhanced permeation and retention effect and was independent of the presence of a targeting ligand. A surprisingly high accumulation in the lymph nodes (˜70% ID/g) was observed. In the 4T1 lymph node metastasis model, the capability of intravenously injected 111In-LCP to visualize the size-enlarged and tumor-loaded sentinel lymph node was demonstrated. By analyzing the SPECT/CT images taken at different time points, the PK profiles of 111In-LCP in the blood and major organs were determined. The results indicated that the decrement of 111In-LCP blood concentration was not due to excretion, but to tissue penetration, leading to lymphatic accumulation. Larger LCP (diameter ˜65 nm) nanoparticles were also prepared for the purpose of comparison. Results indicated that larger LCP achieved slightly lower accumulation in the tumor and lymph nodes, but much higher accumulation in the liver and spleen; thus, larger nanoparticles might not be favorable for imaging purposes. We also demonstrated that LCP with a diameter of ˜25 nm were better able to penetrate into tissues, travel in the lymphatic system and preferentially accumulate in the lymph nodes due to 1) small

  17. Diagnosis of adrenal tumors with radionuclide imaging

    SciTech Connect

    Beierwaltes, W.H.; Sisson, J.C.; Shapiro, B.

    1984-01-01

    The development of radiolabeled cholesterols in 1969 as precursors of adrenocortical steroid production allowed the first noninvasive imaging of the adrenal cortices. FDA-NDA approval in 1984 should allow routine use of these agents in most hospitals. NP-59 is most commonly used in the diagnosis and management of Cushing syndrome; the second most common use is in the diagnosis of primary aldosteronism. It is also helpful in the differential diagnosis of adrenal and ovarian hyperandrogenism and hirsutism, and is the only noninvasive method of detecting unilateral adrenocortical hypofunction. The newest and most popular use is in the differential diagnosis of asymptomatic masses in the region of the adrenal gland discovered incidentally with CT scan (incidentalomas). In this situation, the NP-59 scan can define whether the tumor is in the adrenal gland and if it is functional or nonfunctional. The authors believe that, in the future, radiolabeled enzyme inhibitors might offer better diagnostic imaging of the adrenal cortex, although these agents will probably not be available for routine use for some time. The development of a radioiodinated guanethidine analog, /sup 131/I-MIBG, has allowed differentiation of normal adrenal medullary function from bilateral adrenal medullary hyperplasia before the development of hypertension or tachycardia, diagnostic increases in plasma or urinary catecholamines, or abnormal CT scans. The search for a pheochromocytoma should begin with /sup 131/I-MIBG scintigraphy. While over 90% of primary pheochromocytomas occur in the abdomen, neither a survey of the abdomen nor the finding of a single tumor should conclude the search.

  18. Imaging in neuroendocrine tumors: an update for the clinician

    PubMed Central

    Maxwell, Jessica E; Howe, James R

    2015-01-01

    Neuroendocrine tumors are a heterogeneous group of neoplasms that are best worked up and managed using a variety of clinical and imaging studies. They are often diagnosed after they have already metastasized, though this does not necessarily preclude an attempt at curative surgical treatment or surgical debulking. Tumor burden assessment often requires use of multiple imaging modalities including computed tomography, magnetic resonance imaging and ultrasound. Somatostatin receptor-based imaging is also of great utility in looking for primaries and determining the extent of metastatic disease. This paper will review the most common imaging modalities used in the diagnosis and treatment of neuroendocrine tumors. PMID:26257863

  19. Molecular Imaging in Tumor Angiogenesis and Relevant Drug Research

    PubMed Central

    Ma, Xibo; Tian, Jie; Yang, Xin; Qin, Chenghu

    2011-01-01

    Molecular imaging, including fluorescence imaging (FMI), bioluminescence imaging (BLI), positron emission tomography (PET), single-photon emission-computed tomography (SPECT), and computed tomography (CT), has a pivotal role in the process of tumor and relevant drug research. CT, especially Micro-CT, can provide the anatomic information for a region of interest (ROI); PET and SPECT can provide functional information for the ROI. BLI and FMI can provide optical information for an ROI. Tumor angiogenesis and relevant drug development is a lengthy, high-risk, and costly process, in which a novel drug needs about 10–15 years of testing to obtain Federal Drug Association (FDA) approval. Molecular imaging can enhance the development process by understanding the tumor mechanisms and drug activity. In this paper, we focus on tumor angiogenesis, and we review the characteristics of molecular imaging modalities and their applications in tumor angiogenesis and relevant drug research. PMID:21808639

  20. Functional imaging of tumor vascular network in small animal models

    NASA Astrophysics Data System (ADS)

    Kalchenko, Vyacheslav; Madar-Balakirski, Noa; Kuznetsov, Yuri; Meglinski, Igor; Harmelin, Alon

    2011-07-01

    In current report we present synchronized in vivo imaging of tumor vascular network and tumor microenvironment obtained by combined use of Dynamic Light Scattering Imaging, Spectrally Enhanced Microscopy, and Fluorescence Intravital Microscopy. Dynamic Light Scattering Imaging is used for functional imaging of the vascular network and blood microcirculation. Spectrally Enhanced Microscopy provides information regarding blood vessel topography. Fluorescence Intravital Microscopy is used for imaging of tumor microvasculature and tumor microenvironment. These well known modalities have been comprehensively validated in the past and are widely used in various bio-medical applications. As shown here, their combined application has great potential for studies of vascular biology. This multi-modal non-invasive diagnostic technique expands our current capacity to investigate blood microcirculation and tumor angiogenesis in vivo, thereby contributing to the development of cancer research and treatment.

  1. Round Randomized Learning Vector Quantization for Brain Tumor Imaging

    PubMed Central

    2016-01-01

    Brain magnetic resonance imaging (MRI) classification into normal and abnormal is a critical and challenging task. Owing to that, several medical imaging classification techniques have been devised in which Learning Vector Quantization (LVQ) is amongst the potential. The main goal of this paper is to enhance the performance of LVQ technique in order to gain higher accuracy detection for brain tumor in MRIs. The classical way of selecting the winner code vector in LVQ is to measure the distance between the input vector and the codebook vectors using Euclidean distance function. In order to improve the winner selection technique, round off function is employed along with the Euclidean distance function. Moreover, in competitive learning classifiers, the fitting model is highly dependent on the class distribution. Therefore this paper proposed a multiresampling technique for which better class distribution can be achieved. This multiresampling is executed by using random selection via preclassification. The test data sample used are the brain tumor magnetic resonance images collected from Universiti Kebangsaan Malaysia Medical Center and UCI benchmark data sets. Comparative studies showed that the proposed methods with promising results are LVQ1, Multipass LVQ, Hierarchical LVQ, Multilayer Perceptron, and Radial Basis Function. PMID:27516807

  2. Round Randomized Learning Vector Quantization for Brain Tumor Imaging.

    PubMed

    Sheikh Abdullah, Siti Norul Huda; Bohani, Farah Aqilah; Nayef, Baher H; Sahran, Shahnorbanun; Al Akash, Omar; Iqbal Hussain, Rizuana; Ismail, Fuad

    2016-01-01

    Brain magnetic resonance imaging (MRI) classification into normal and abnormal is a critical and challenging task. Owing to that, several medical imaging classification techniques have been devised in which Learning Vector Quantization (LVQ) is amongst the potential. The main goal of this paper is to enhance the performance of LVQ technique in order to gain higher accuracy detection for brain tumor in MRIs. The classical way of selecting the winner code vector in LVQ is to measure the distance between the input vector and the codebook vectors using Euclidean distance function. In order to improve the winner selection technique, round off function is employed along with the Euclidean distance function. Moreover, in competitive learning classifiers, the fitting model is highly dependent on the class distribution. Therefore this paper proposed a multiresampling technique for which better class distribution can be achieved. This multiresampling is executed by using random selection via preclassification. The test data sample used are the brain tumor magnetic resonance images collected from Universiti Kebangsaan Malaysia Medical Center and UCI benchmark data sets. Comparative studies showed that the proposed methods with promising results are LVQ1, Multipass LVQ, Hierarchical LVQ, Multilayer Perceptron, and Radial Basis Function. PMID:27516807

  3. Feasibility Study of Dual Energy Radiographic Imaging for Target Localization in Radiotherapy for Lung Tumors

    PubMed Central

    Huo, Jie; Zhu, Xianfeng; Dong, Yang; Yuan, Zhiyong; Wang, Ping; Wang, Xuemin; Wang, Gang; Hu, Xin-Hua; Feng, Yuanming

    2014-01-01

    Purpose Dual-energy (DE) radiographic imaging improves tissue discrimination by separating soft from hard tissues in the acquired images. This study was to establish a mathematic model of DE imaging based on intrinsic properties of tissues and quantitatively evaluate the feasibility of applying the DE imaging technique to tumor localization in radiotherapy. Methods We investigated the dependence of DE image quality on the radiological equivalent path length (EPL) of tissues with two phantoms using a stereoscopic x-ray imaging unit. 10 lung cancer patients who underwent radiotherapy each with gold markers implanted in the tumor were enrolled in the study approved by the hospital's Ethics Committee. The displacements of the centroids of the delineated gross tumor volumes (GTVs) in the digitally reconstructed radiograph (DRR) and in the bone-canceled DE image were compared with the averaged displacements of the centroids of gold markers to evaluate the feasibility of using DE imaging for tumor localization. Results The results of the phantom study indicated that the contrast-to-noise ratio (CNR) was linearly dependent on the difference of EPL and a mathematical model was established. The objects and backgrounds corresponding to ΔEPL less than 0.08 are visually indistinguishable in the bone-canceled DE image. The analysis of patient data showed that the tumor contrast in the bone-canceled images was improved significantly as compared with that in the original radiographic images and the accuracy of tumor localization using the DE imaging technique was comparable with that of using fiducial makers. Conclusion It is feasible to apply the technique for tumor localization in radiotherapy. PMID:25268643

  4. Gradient-Based Algorithm for Determining Tumor Volumes in Small Animals Using Planar Fluorescence Imaging Platform

    PubMed Central

    Miller, Jessica P.; Egbulefu, Christopher; Prior, Julie L.; Zhou, Mingzhou; Achilefu, Samuel

    2016-01-01

    Planar fluorescence imaging is widely used in biological research because of its simplicity, use of non-ionizing radiation, and high-throughput data acquisition. In cancer research, where small animal models are used to study the in vivo effects of cancer therapeutics, the output of interest is often the tumor volume. Unfortunately, inaccuracies in determining tumor volume from surface-weighted projection fluorescence images undermine the data, and alternative physical or conventional tomographic approaches are prone to error or are tedious for most laboratories. Here, we report a method that uses a priori knowledge of a tumor xenograft model, a tumor-targeting near infrared probe, and a custom-developed image analysis planar view tumor volume algorithm (PV-TVA) to estimate tumor volume from planar fluorescence images. Our algorithm processes images obtained using near infrared light for improving imaging depth in tissue in comparison with light in the visible spectrum. We benchmarked our results against the actual tumor volume obtained from a standard water volume displacement method. Compared with a caliper-based method that has an average deviation from an actual volume of 18% (204.34 ± 115.35 mm3), our PV-TVA average deviation from the actual volume was 9% (97.24 ± 70.45 mm3; P < .001). Using a normalization-based analysis, we found that bioluminescence imaging and PV-TVA average deviations from actual volume were 36% and 10%, respectively. The improved accuracy of tumor volume assessment from planar fluorescence images, rapid data analysis, and the ease of archiving images for subsequent retrieval and analysis potentially lend our PV-TVA method to diverse cancer imaging applications. PMID:27200417

  5. Imaging of Tumor Metabolism Using Positron Emission Tomography (PET).

    PubMed

    Apostolova, Ivayla; Wedel, Florian; Brenner, Winfried

    2016-01-01

    Molecular imaging employing PET/CT enables in vivo visualization, characterization, and measurement of biologic processes in tumors at a molecular and cellular level. Using specific metabolic tracers, information about the integrated function of multiple transporters and enzymes involved in tumor metabolic pathways can be depicted, and the tracers can be directly applied as biomarkers of tumor biology. In this review, we discuss the role of F-18-fluorodeoxyglucose (FDG) as an in vivo glycolytic marker which reflects alterations of glucose metabolism in cancer cells. This functional molecular imaging technique offers a complementary approach to anatomic imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) and has found widespread application as a diagnostic modality in oncology to monitor tumor biology, optimize the therapeutic management, and guide patient care. Moreover, emerging methods for PET imaging of further biologic processes relevant to cancer are reviewed, with a focus on tumor hypoxia and aberrant tumor perfusion. Hypoxic tumors are associated with poor disease control and increased resistance to cytotoxic and radiation treatment. In vivo imaging of hypoxia, perfusion, and mismatch of metabolism and perfusion has the potential to identify specific features of tumor microenvironment associated with poor treatment outcome and, thus, contribute to personalized treatment approaches. PMID:27557539

  6. Telltale signs of peripheral neurogenic tumors on magnetic resonance imaging

    PubMed Central

    Kakkar, Chandan; Shetty, Chandrakant M; Koteshwara, Prakashini; Bajpai, Surabhi

    2015-01-01

    Peripheral nerve sheath tumors are categorized into benign and malignant forms, comprising of neurofibroma and schwannoma in the benign category and malignant peripheral nerve sheath tumors in the malignant category. Magnetic resonance imaging plays an important role in the diagnosis of these lesions. The various imaging features and signs that help to identify and characterize a nerve sheath tumor are, distribution of the tumor along a major nerve, an entering or exiting nerve sign, target sign, a fascicular sign and a split-fat sign. PMID:26752825

  7. Telltale signs of peripheral neurogenic tumors on magnetic resonance imaging.

    PubMed

    Kakkar, Chandan; Shetty, Chandrakant M; Koteshwara, Prakashini; Bajpai, Surabhi

    2015-01-01

    Peripheral nerve sheath tumors are categorized into benign and malignant forms, comprising of neurofibroma and schwannoma in the benign category and malignant peripheral nerve sheath tumors in the malignant category. Magnetic resonance imaging plays an important role in the diagnosis of these lesions. The various imaging features and signs that help to identify and characterize a nerve sheath tumor are, distribution of the tumor along a major nerve, an entering or exiting nerve sign, target sign, a fascicular sign and a split-fat sign. PMID:26752825

  8. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  9. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    PubMed Central

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-01-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue. PMID:27456312

  10. Intraoperative near-infrared fluorescence imaging and spectroscopy identifies residual tumor cells in wounds

    PubMed Central

    Holt, David; Parthasarathy, Ashwin B.; Okusanya, Olugbenga; Keating, Jane; Venegas, Ollin; Deshpande, Charuhas; Karakousis, Giorgos; Madajewski, Brian; Durham, Amy; Nie, Shuming; Yodh, Arjun G.; Singhal, Sunil

    2015-01-01

    Abstract. Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14/15 canines with a mean fluorescence signal-to-background ratio (SBR) of ∼16. Ten animals showed no residual tumor cells in the wound bed (mean SBR<2, P<0.001). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15, and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations. PMID:26160347

  11. Intraoperative near-infrared fluorescence imaging and spectroscopy identifies residual tumor cells in wounds

    NASA Astrophysics Data System (ADS)

    Holt, David; Parthasarathy, Ashwin B.; Okusanya, Olugbenga; Keating, Jane; Venegas, Ollin; Deshpande, Charuhas; Karakousis, Giorgos; Madajewski, Brian; Durham, Amy; Nie, Shuming; Yodh, Arjun G.; Singhal, Sunil

    2015-07-01

    Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14/15 canines with a mean fluorescence signal-to-background ratio (SBR) of ˜16. Ten animals showed no residual tumor cells in the wound bed (mean SBR<2, P<0.001). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15, and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations.

  12. Intraoperative near-infrared fluorescence imaging and spectroscopy identifies residual tumor cells in wounds.

    PubMed

    Holt, David; Parthasarathy, Ashwin B; Okusanya, Olugbenga; Keating, Jane; Venegas, Ollin; Deshpande, Charuhas; Karakousis, Giorgos; Madajewski, Brian; Durham, Amy; Nie, Shuming; Yodh, Arjun G; Singhal, Sunil

    2015-07-01

    Surgery is the most effective method to cure patients with solid tumors, and 50% of all cancer patients undergo resection. Local recurrences are due to tumor cells remaining in the wound, thus we explore near-infrared (NIR) fluorescence spectroscopy and imaging to identify residual cancer cells after surgery. Fifteen canines and two human patients with spontaneously occurring sarcomas underwent intraoperative imaging. During the operation, the wounds were interrogated with NIR fluorescence imaging and spectroscopy. NIR monitoring identified the presence or absence of residual tumor cells after surgery in 14/15 canines with a mean fluorescence signal-to-background ratio (SBR) of ∼16 . Ten animals showed no residual tumor cells in the wound bed (mean SBR<2 , P<0.001 ). None had a local recurrence at >1-year follow-up. In five animals, the mean SBR of the wound was >15 , and histopathology confirmed tumor cells in the postsurgical wound in four/five canines. In the human pilot study, neither patient had residual tumor cells in the wound bed, and both remain disease free at >1.5-year follow up. Intraoperative NIR fluorescence imaging and spectroscopy identifies residual tumor cells in surgical wounds. These observations suggest that NIR imaging techniques may improve tumor resection during cancer operations. PMID:26160347

  13. Evaluating image reconstruction methods for tumor detection performance in whole-body PET oncology imaging

    NASA Astrophysics Data System (ADS)

    Lartizien, Carole; Kinahan, Paul E.; Comtat, Claude; Lin, Michael; Swensson, Richard G.; Trebossen, Regine; Bendriem, Bernard

    2000-04-01

    This work presents initial results from observer detection performance studies using the same volume visualization software tools that are used in clinical PET oncology imaging. Research into the FORE+OSEM and FORE+AWOSEM statistical image reconstruction methods tailored to whole- body 3D PET oncology imaging have indicated potential improvements in image SNR compared to currently used analytic reconstruction methods (FBP). To assess the resulting impact of these reconstruction methods on the performance of human observers in detecting and localizing tumors, we use a non- Monte Carlo technique to generate multiple statistically accurate realizations of 3D whole-body PET data, based on an extended MCAT phantom and with clinically realistic levels of statistical noise. For each realization, we add a fixed number of randomly located 1 cm diam. lesions whose contrast is varied among pre-calibrated values so that the range of true positive fractions is well sampled. The observer is told the number of tumors and, similar to the AFROC method, asked to localize all of them. The true positive fraction for the three algorithms (FBP, FORE+OSEM, FORE+AWOSEM) as a function of lesion contrast is calculated, although other protocols could be compared. A confidence level for each tumor is also recorded for incorporation into later AFROC analysis.

  14. Semantic Reasoning with Image Annotations for Tumor Assessment

    PubMed Central

    Levy, Mia A.; O’Connor, Martin J.; Rubin, Daniel L.

    2009-01-01

    Identifying, tracking and reasoning about tumor lesions is a central task in cancer research and clinical practice that could potentially be automated. However, information about tumor lesions in imaging studies is not easily accessed by machines for automated reasoning. The Annotation and Image Markup (AIM) information model recently developed for the cancer Biomedical Informatics Grid provides a method for encoding the semantic information related to imaging findings, enabling their storage and transfer. However, it is currently not possible to apply automated reasoning methods to image information encoded in AIM. We have developed a methodology and a suite of tools for transforming AIM image annotations into OWL, and an ontology for reasoning with the resulting image annotations for tumor lesion assessment. Our methods enable automated inference of semantic information about cancer lesions in images. PMID:20351880

  15. Prognostication and response assessment in liver and pancreatic tumors: The new imaging.

    PubMed

    De Robertis, Riccardo; Tinazzi Martini, Paolo; Demozzi, Emanuele; Puntel, Gino; Ortolani, Silvia; Cingarlini, Sara; Ruzzenente, Andrea; Guglielmi, Alfredo; Tortora, Giampaolo; Bassi, Claudio; Pederzoli, Paolo; D'Onofrio, Mirko

    2015-06-14

    Diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term "functional imaging" is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive "one-step" morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for post-treatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart from molecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations, prognostic stratification and post-treatment monitoring. PMID:26078555

  16. Mucin-producing tumors of the ovary: MR imaging appearance.

    PubMed

    Laurent, P-E; Thomassin-Piana, J; Jalaguier-Coudray, A

    2015-11-01

    Mucin-producing tumors of the ovary can be either primary epithelial mucin-producing tumors or ovarian metastases from a remote adenocarcinoma usually originating from the gastrointestinal tract. The purpose of this pictorial review is to describe the main types of primary or secondary mucin-producing tumors of the ovary and to provide MR imaging diagnostic criteria in order to guide further therapy. PMID:25753545

  17. CARS and non-linear microscopy imaging of brain tumors

    NASA Astrophysics Data System (ADS)

    Galli, Roberta; Uckermann, Ortrud; Tamosaityte, Sandra; Geiger, Kathrin; Schackert, Gabriele; Steiner, Gerald; Koch, Edmund; Kirsch, Matthias

    2013-06-01

    Nonlinear optical microscopy offers a series of techniques that have the potential to be applied in vivo, for intraoperative identification of tumor border and in situ pathology. By addressing the different content of lipids that characterize the tumors with respect to the normal brain tissue, CARS microscopy enables to discern primary and secondary brain tumors from healthy tissue. A study performed in mouse models shows that the reduction of the CARS signal is a reliable quantity to identify brain tumors, irrespective from the tumor type. Moreover it enables to identify tumor borders and infiltrations at a cellular resolution. Integration of CARS with autogenous TPEF and SHG adds morphological and compositional details about the tissue. Examples of multimodal CARS imaging of different human tumor biopsies demonstrate the ability of the technique to retrieve information useful for histopathological diagnosis.

  18. High-Resolution Multiphoton Imaging of Tumors In Vivo

    PubMed Central

    Wyckoff, Jeffrey; Gligorijevic, Bojana; Entenberg, David; Segall, Jeffrey; Condeelis, John

    2014-01-01

    Analysis of the individual steps in metastasis is crucial if insights at the molecular level are to be linked to the cell biology of cancer. A technical hurdle to achieving the analysis of the individual steps of metastasis is the fact that, at the gross level, tumors are heterogeneous in both animal models and patients. Human primary tumors show extensive variation in all properties ranging from growth and morphology of the tumor through tumor-cell density in the blood and formation and growth of metastases. Methods capable of the direct visualization and analysis of tumor-cell behavior at single-cell resolution in vivo have become crucial in advancing the understanding of mechanisms of metastasis, the definition of microenvironment, and the markers related to both. This article discusses the use of high-resolution multiphoton imaging of tumors (specifically breast tumors in mice) in vivo. PMID:21969629

  19. Prognostication and response assessment in liver and pancreatic tumors: The new imaging

    PubMed Central

    De Robertis, Riccardo; Tinazzi Martini, Paolo; Demozzi, Emanuele; Puntel, Gino; Ortolani, Silvia; Cingarlini, Sara; Ruzzenente, Andrea; Guglielmi, Alfredo; Tortora, Giampaolo; Bassi, Claudio; Pederzoli, Paolo; D’Onofrio, Mirko

    2015-01-01

    Diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and perfusion computed tomography (CT) are technical improvements of morphologic imaging that can evaluate functional properties of hepato-bilio-pancreatic tumors during conventional MRI or CT examinations. Nevertheless, the term “functional imaging” is commonly used to describe molecular imaging techniques, as positron emission tomography (PET) CT/MRI, which still represent the most widely used methods for the evaluation of functional properties of solid neoplasms; unlike PET or single photon emission computed tomography, functional imaging techniques applied to conventional MRI/CT examinations do not require the administration of radiolabeled drugs or specific equipments. Moreover, DWI and DCE-MRI can be performed during the same session, thus providing a comprehensive “one-step” morphological and functional evaluation of hepato-bilio-pancreatic tumors. Literature data reveal that functional imaging techniques could be proposed for the evaluation of these tumors before treatment, given that they may improve staging and predict prognosis or clinical outcome. Microscopic changes within neoplastic tissues induced by treatments can be detected and quantified with functional imaging, therefore these techniques could be used also for post-treatment assessment, even at an early stage. The aim of this editorial is to describe possible applications of new functional imaging techniques apart from molecular imaging to hepatic and pancreatic tumors through a review of up-to-date literature data, with a particular emphasis on pathological correlations, prognostic stratification and post-treatment monitoring. PMID:26078555

  20. Current and Future Lymphatic Imaging Modalities for Tumor Staging

    PubMed Central

    Gao, Kuo; Liu, Tiegang; Tariq, Imran; Sajjad, Ashif; Niu, Meiying; Liu, Guokai; Mehmood, Zahid; Tian, Guihua

    2014-01-01

    Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review. PMID:24757671

  1. Current and future lymphatic imaging modalities for tumor staging.

    PubMed

    Murtaza, Ghulam; Gao, Kuo; Liu, Tiegang; Tariq, Imran; Sajjad, Ashif; Akram, Muhammad Rouf; Niu, Meiying; Liu, Guokai; Mehmood, Zahid; Tian, Guihua

    2014-01-01

    Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review. PMID:24757671

  2. NSCLC tumor shrinkage prediction using quantitative image features.

    PubMed

    Hunter, Luke A; Chen, Yi Pei; Zhang, Lifei; Matney, Jason E; Choi, Haesun; Kry, Stephen F; Martel, Mary K; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel; Yang, Jinzhong; Court, Laurence E

    2016-04-01

    The objective of this study was to develop a quantitative image feature model to predict non-small cell lung cancer (NSCLC) volume shrinkage from pre-treatment CT images. 64 stage II-IIIB NSCLC patients with similar treatments were all imaged using the same CT scanner and protocol. For each patient, the planning gross tumor volume (GTV) was deformed onto the week 6 treatment image, and tumor shrinkage was quantified as the deformed GTV volume divided by the planning GTV volume. Geometric, intensity histogram, absolute gradient image, co-occurrence matrix, and run-length matrix image features were extracted from each planning GTV. Prediction models were generated using principal component regression with simulated annealing subset selection. Performance was quantified using the mean squared error (MSE) between the predicted and observed tumor shrinkages. Permutation tests were used to validate the results. The optimal prediction model gave a strong correlation between the observed and predicted tumor shrinkages with r=0.81 and MSE=8.60×10(-3). Compared to predictions based on the mean population shrinkage this resulted in a 2.92 fold reduction in MSE. In conclusion, this study indicated that quantitative image features extracted from existing pre-treatment CT images can successfully predict tumor shrinkage and provide additional information for clinical decisions regarding patient risk stratification, treatment, and prognosis. PMID:26878137

  3. A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

    PubMed

    Scheepbouwer, Chantal; Meyer, Sandra; Burggraaf, Maroeska J; Jose, Jithin; Molthoff, Carla F M

    2016-01-01

    Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new) agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics. PMID:27533303

  4. A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model

    PubMed Central

    Meyer, Sandra; Burggraaf, Maroeska J.; Jose, Jithin; Molthoff, Carla F. M.

    2016-01-01

    Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new) agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics. PMID:27533303

  5. Early detection of postoperative residual tumor using image subtraction

    NASA Astrophysics Data System (ADS)

    Narayan, Suresh B.; Dhawan, Atam P.; Taha, Jamal M.; Gaskill-Shipley, Mary; Lamba, Michael; Sarwal, Alok; Chitre, Yateen S.

    1995-05-01

    The detection after surgery of residual tumor from magnetic resonance (MR) images is difficult due to the low contrast level of the images. Gadolinium-enhanced MR imaging has been found valuable in detecting residual enhancing tumor when performed within 72 hours after surgery. The patient is scanned by the MR scanner with and without infusion of gadolinium, a contrast agent. Usually, the estimation of post-operative tumor volume is done by visual comparison of the T1 MR images obtained with and without gadolinium infusion. The T1 MR images, in most cases, without contrast demonstrates areas of hyper intensities (high brightness levels), consistent with hemorrhage. These hyper intense areas often make it difficult to detect residual tumor in post contrast images. This is due to the presence of both acute hemorrhage and gadolinium enhancement which have high brightness levels in T1 MR images. Even in MR images taken within 72 hours after surgery, detection of tumor enhancement in areas of increased T1 signal produced by blood products or by postoperative changes can be difficult when performed by the naked eye. Due to these problems, the quantification of residual tumor becomes a subjective issue among neuro-radiologists. Thus to reduce errors produced by the human factor, an automated procedure to detect residual tumor is required. We have developed a technique to differentiate tumor enhancement from postoperative changes and blood products on MR imaging. The technique involves fusion of pre- and post-gadolinium MR images performed in the immediate postoperative period. Computerized slice based substraction is then done on the corresponding fused images of the two sets. The subtraction process results in a composite slice, which is examined for differences between pre- and post-gadolinium studies. The presented technique was tested on 14 cases in which MR images were obtained from brain tumor patients within 72 hours after surgery. The subtraction technique easily

  6. Preferential tumor cellular uptake and retention of indocyanine green for in vivo tumor imaging.

    PubMed

    Onda, Nobuhiko; Kimura, Masayuki; Yoshida, Toshinori; Shibutani, Makoto

    2016-08-01

    Indocyanine green (ICG) is a fluorescent agent approved for clinical applications by the Food and Drug Administration and European Medicines Agency. This study examined the mechanism of tumor imaging using intravenously administered ICG. The in vivo kinetics of intravenously administered ICG were determined in tumor xenografts using microscopic approaches that enabled both spatio-temporal and high-magnification analyses. The mechanism of ICG-based tumor imaging was examined at the cellular level in six phenotypically different human colon cancer cell lines exhibiting different grades of epithelioid organization. ICG fluorescence imaging detected xenograft tumors, even those < 1 mm in size, based on their preferential cellular uptake and retention of the dye following its rapid tissue-non-specific delivery, in contrast to its rapid clearance by normal tissue. Live-cell imaging revealed that cellular ICG uptake is temperature-dependent and occurs after ICG binding to the cellular membrane, a pattern suggesting endocytic uptake as the mechanism. Cellular ICG uptake correlated inversely with the formation of tight junctions. Intracellular ICG was entrapped in the membrane traffic system, resulting in its slow turnover and prolonged retention by tumor cells. Our results suggest that tumor-specific imaging by ICG involves non-specific delivery of the dye to tissues followed by preferential tumor cellular uptake and retention. The tumor cell-preference of ICG is driven by passive tumor cell-targeting, the inherent ability of ICG to bind to cell membranes, and the high endocytic activity of tumor cells in association with the disruption of their tight junctions. PMID:27006261

  7. Multimodal system for in vivo tumor imaging in mice

    NASA Astrophysics Data System (ADS)

    Autiero, Maddalena; Celentano, Luigi; Cozzolino, Rosanna; Laccetti, Paolo; Marotta, Marcello; Mettivier, Giovanni; Montesi, Maria Cristina; Riccio, Patrizia; Roberti, Giuseppe; Russo, Paolo

    2006-04-01

    We devised a multimodal planar imaging system for in vivo mouse imaging, employing four modalities: optical imaging, green and red fluorescence reflectance imaging, radionuclide imaging and X-ray radiography. We are testing separately, and then in a combined way, each detection mode, via in vivo mouse imaging, with the final purpose of identifying small implanted tumor masses, of providing early tumor detection and following metastatic dissemination. We describe the multimodal system and summarize its main performance, as assessed in our research work in the various stages of the development, in fluorescence and radionuclide tests on healthy or tumor bearing mice. For gamma-ray detection we used a semiconductor pixel detector (Medipix1 or Medipix2) that works in single photon counting. Laser-induced fluorescence reflectance imaging was performed in vivo using a pulsed light source to excite the fluorescence emission of injected hematoporphyrin (HP) compound, a CCD camera, a low pass filter and a commercial image analysis system. The bimodal system was used for the acquisition of combined images of the tumor area (fluorescence: animal top view; radionuclide: bottom view). It was shown that the tumor area can be imaged in a few minutes, with a few millimeter resolution (1 mm pinhole diameter), radioactively ( 99mTc radiotracer), and with the fluorescence system and that, in one case, only one of the two modalities is able to recognize the tumor. A phantom study for thyroid imaging with 125I source embedded in a simulated tissue indicated a spatial resolution of 1.25 mm FWHM with a 1 mm pinhole.

  8. Primary spinal primitive neuroectodermal tumor on MR imaging.

    PubMed

    Thoriya, Prashant J; Watal, Pankaj; Bahri, Nandini U; Rathod, Ketan

    2015-01-01

    Neoplasms in the region of filum terminale are not uncommon. Myxopapillary ependymoma is the commonest tumor at this location. The differentials reported for this entity are nerve sheath tumor, meningioma, paraganglioma, intradural metastases, lymphoma, other varieties of ependymoma, subependymoma, astrocytoma, ganglioglioma, hemangioblastoma, and primitive neuroectodermal tumor (PNET). PNET may very rarely present as an intradural thoracolumbar mass. We present pre- and post-therapy magnetic resonance imaging (MRI) features of a patient with proven primary spinal primitive neuroectodermal tumor (PSPNET) of peripheral subtype. PMID:26752826

  9. Primary spinal primitive neuroectodermal tumor on MR imaging

    PubMed Central

    Thoriya, Prashant J; Watal, Pankaj; Bahri, Nandini U; Rathod, Ketan

    2015-01-01

    Neoplasms in the region of filum terminale are not uncommon. Myxopapillary ependymoma is the commonest tumor at this location. The differentials reported for this entity are nerve sheath tumor, meningioma, paraganglioma, intradural metastases, lymphoma, other varieties of ependymoma, subependymoma, astrocytoma, ganglioglioma, hemangioblastoma, and primitive neuroectodermal tumor (PNET). PNET may very rarely present as an intradural thoracolumbar mass. We present pre- and post-therapy magnetic resonance imaging (MRI) features of a patient with proven primary spinal primitive neuroectodermal tumor (PSPNET) of peripheral subtype. PMID:26752826

  10. Modulation of the Tumor Vasculature and Oxygenation to Improve Therapy

    PubMed Central

    Siemann, Dietmar W.; Horsman, Michael R.

    2015-01-01

    The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient nutritional support to tumor cells. As a consequence the expanding neoplastic cell population initiates its own vascular network which is both structurally and functionally abnormal. This aberrant vasculature impacts all aspects of the tumor microenvironment including the cells, extracellular matrix, and extracellular molecules which together are essential for the initiation, progression and spread of tumor cells. The physical conditions that arise are imposing and manifold, and include elevated interstitial pressure, localized extracellular acidity, and regions of oxygen and nutrient deprivation. No less important are the functional consequences experienced by the tumor cells residing in such environments: adaptation to hypoxia, cell quiescence, modulation of transporters and critical signaling molecules, immune escape, and enhanced metastatic potential. Together these factors lead to therapeutic barriers that create a significant hindrance to the control of cancers by conventional anticancer therapies. However, the aberrant nature of the tumor microenvironments also offers unique therapeutic opportunities. Particularly interventions that seek to improve tumor physiology and alleviate tumor hypoxia will selectively impair the neoplastic cell populations residing in these environments. Ultimately, by combining such therapeutic strategies with conventional anticancer treatments it may be possible to bring cancer growth, invasion, and metastasis to a halt. PMID:26073310

  11. Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery

    NASA Astrophysics Data System (ADS)

    Spinelli, Antonello Enrico; Schiariti, Marco P.; Grana, Chiara M.; Ferrari, Mahila; Cremonesi, Marta; Boschi, Federico

    2016-05-01

    We presented the first example of Cerenkov luminescence imaging (CLI) and radioluminescence imaging (RLI) of human tumor specimens. A patient with a brain meningioma localized in the left parietal region was injected with 166 MBq of Y90-DOTATOC the day before neurosurgery. The specimens of the tumor removed during surgery were imaged using both CLI and RLI using an optical imager prototype developed in our laboratory. The system is based on a cooled electron multiplied charge coupled device coupled with an f/0.95 17-mm C-mount lens. We showed for the first time the possibility of obtaining CLI and RLI images of fresh human brain tumor specimens removed during neurosurgery.

  12. Evaluation of a targeted nanobubble ultrasound contrast agent for potential tumor imaging

    NASA Astrophysics Data System (ADS)

    Li, Chunfang; Shen, Chunxu; Liu, Haijuan; Wu, Kaizhi; Zhou, Qibing; Ding, Mingyue

    2015-03-01

    Targeted nanobubbles have been reported to improve the contrast effect of ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, the contrast enhancement abilities and the tumor targeting potential of a self-made VEGFR2-targeted nanobubble ultrasound contrast agent was evaluated in-vitro and in-vivo. Size distribution and zeta potential were assessed. Then the contrast-enhanced ultrasound imaging of the VEGFR2 targeted nanobubbles were evaluated with a custom-made experimental apparatus and in normal Wistar rats. Finally, the in-vivo tumor-targeting ability was evaluated on nude mice with subcutaneous tumor. The results showed that the target nanobubbles had uniform distribution with the average diameter of 208.1 nm, polydispersity index (PDI) of 0.411, and zeta potential of -13.21 mV. Significant contrast enhancement was observed in both in-vitro and in-vivo ultrasound imaging, demonstrating that the self-made target nanobubbles can enhance the contrast effect of ultrasound imaging efficiently. Targeted tumor imaging showed less promising result, due to the fact that the targeted nanobubbles arriving and permeating through tumor vessels were not many enough to produce significant enhancement. Future work will focus on exploring new imaging algorithm which is sensitive to targeted nanobubbles, so as to correctly detect the contrast agent, particularly at a low bubble concentration.

  13. Improving the distribution of Doxil® in the tumor matrix by depletion of tumor hyaluronan.

    PubMed

    Kohli, Aditya G; Kivimäe, Saul; Tiffany, Matthew R; Szoka, Francis C

    2014-10-10

    Liposomes improve the pharmacokinetics and safety of rapidly cleared drugs, but have not yet improved the clinical efficacy compared to the non-encapsulated drug. This inability to improve efficacy may be partially due to the non-uniform distribution of liposomes in solid tumors. The tumor extra-cellular matrix is a barrier to distribution and includes the high molecular weight glycosaminoglycan, hyaluronan (HA). Strategies to remove HA or block its synthesis may improve drug delivery into solid tumors. Orally administered methylumbelliferone (MU) is an inhibitor of HA synthesis, but it is limited by low potency and limited solubility. In this study, we encapsulate a water-soluble phosphorylated prodrug of MU (MU-P) in a liposome (L-MU-P). We demonstrate that L-MU-P is a more potent inhibitor of HA synthesis than oral MU in the 4T1 murine mammary carcinoma model using both a quantitative ELISA and histochemistry. We show that HA depletion improves the tumor distribution of liposomes computed using Mander's colocalization analysis of liposomes with the tumor vasculature. Hyaluronan depletion also increases the fraction of the tumor area positive for liposomes. This improved distribution extends the overall survival of mice treated with Doxil®. PMID:24852095

  14. Fluoroscopic tumor tracking for image-guided lung cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Lin, Tong; Cerviño, Laura I.; Tang, Xiaoli; Vasconcelos, Nuno; Jiang, Steve B.

    2009-02-01

    Accurate lung tumor tracking in real time is a keystone to image-guided radiotherapy of lung cancers. Existing lung tumor tracking approaches can be roughly grouped into three categories: (1) deriving tumor position from external surrogates; (2) tracking implanted fiducial markers fluoroscopically or electromagnetically; (3) fluoroscopically tracking lung tumor without implanted fiducial markers. The first approach suffers from insufficient accuracy, while the second may not be widely accepted due to the risk of pneumothorax. Previous studies in fluoroscopic markerless tracking are mainly based on template matching methods, which may fail when the tumor boundary is unclear in fluoroscopic images. In this paper we propose a novel markerless tumor tracking algorithm, which employs the correlation between the tumor position and surrogate anatomic features in the image. The positions of the surrogate features are not directly tracked; instead, we use principal component analysis of regions of interest containing them to obtain parametric representations of their motion patterns. Then, the tumor position can be predicted from the parametric representations of surrogates through regression. Four regression methods were tested in this study: linear and two-degree polynomial regression, artificial neural network (ANN) and support vector machine (SVM). The experimental results based on fluoroscopic sequences of ten lung cancer patients demonstrate a mean tracking error of 2.1 pixels and a maximum error at a 95% confidence level of 4.6 pixels (pixel size is about 0.5 mm) for the proposed tracking algorithm.

  15. Tracking tumor boundary in MV-EPID images without implanted markers: A feasibility study

    SciTech Connect

    Zhang, Xiaoyong Homma, Noriyasu; Ichiji, Kei; Takai, Yoshihiro; Yoshizawa, Makoto

    2015-05-15

    tumor boundary in EPID images by using a LSM-based algorithm. Experimental results conducted on phantom and clinical EPID images demonstrated the effectiveness of the tracking algorithm for visible tumor target. Compared with previous tracking methods, the authors’ algorithm has the potential to improve the tracking accuracy in radiation therapy. In addition, real-time tumor boundary information within the irradiation field will be potentially useful for further applications, such as adaptive beam delivery, dose evaluation.

  16. Assessment of tumor response on MR imaging after locoregional therapy.

    PubMed

    Vossen, Josephina A; Buijs, Manon; Kamel, Ihab R

    2006-09-01

    Assessment of tumor response after locoregional therapies is important in determining treatment success and in guiding future therapy. Magnetic resonance imaging plays an important role in evaluating treatment response to new therapies directed toward hepatic lesion treatment. The traditional and accepted criteria to determine tumor response in oncology, namely the Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) criteria, use decrease in tumor size and lesion enhancement as an indicator of successful therapy. A more recent evaluation method is the Apparent Diffusion Coefficient (ADC) measured by diffusion-weighted MR imaging. Diffusion-weighted MR imaging and ADC values map the thermally induced motion of water molecules in tissues and thereby are able to provide insight into tumor microstructure. In this article we discuss the role of MR imaging in assessing treatment response after various locoregional therapies. We describe the role of tumor size and lesion enhancement as well as ADC mapping. We also discuss the magnetic resonance imaging findings after radiofrequency ablation (RFA), transarterial chemoembolization (TACE) and radioembolization. PMID:17561215

  17. Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions

    PubMed Central

    Liang, Wenjie; Ni, Yicheng; Chen, Feng

    2016-01-01

    The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy. PMID:26812886

  18. Magnetoacoustic imaging of human liver tumor with magnetic induction

    NASA Astrophysics Data System (ADS)

    Hu, Gang; Cressman, Erik; He, Bin

    2011-01-01

    Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues.

  19. Improving the accuracy of brain tumor surgery via Raman-based technology

    PubMed Central

    Hollon, Todd; Lewis, Spencer; Freudiger, Christian W.; Xie, X. Sunney; Orringer, Daniel A.

    2016-01-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors. PMID:26926067

  20. Improving the accuracy of brain tumor surgery via Raman-based technology.

    PubMed

    Hollon, Todd; Lewis, Spencer; Freudiger, Christian W; Sunney Xie, X; Orringer, Daniel A

    2016-03-01

    Despite advances in the surgical management of brain tumors, achieving optimal surgical results and identification of tumor remains a challenge. Raman spectroscopy, a laser-based technique that can be used to nondestructively differentiate molecules based on the inelastic scattering of light, is being applied toward improving the accuracy of brain tumor surgery. Here, the authors systematically review the application of Raman spectroscopy for guidance during brain tumor surgery. Raman spectroscopy can differentiate normal brain from necrotic and vital glioma tissue in human specimens based on chemical differences, and has recently been shown to differentiate tumor-infiltrated tissues from noninfiltrated tissues during surgery. Raman spectroscopy also forms the basis for coherent Raman scattering (CRS) microscopy, a technique that amplifies spontaneous Raman signals by 10,000-fold, enabling real-time histological imaging without the need for tissue processing, sectioning, or staining. The authors review the relevant basic and translational studies on CRS microscopy as a means of providing real-time intraoperative guidance. Recent studies have demonstrated how CRS can be used to differentiate tumor-infiltrated tissues from noninfiltrated tissues and that it has excellent agreement with traditional histology. Under simulated operative conditions, CRS has been shown to identify tumor margins that would be undetectable using standard bright-field microscopy. In addition, CRS microscopy has been shown to detect tumor in human surgical specimens with near-perfect agreement to standard H & E microscopy. The authors suggest that as the intraoperative application and instrumentation for Raman spectroscopy and imaging matures, it will become an essential component in the neurosurgical armamentarium for identifying residual tumor and improving the surgical management of brain tumors. PMID:26926067

  1. Tumor-Targeted Multimodal Optical Imaging with Versatile Cadmium-Free Quantum Dots

    PubMed Central

    Liu, Xiangyou; Braun, Gary B.; Zhong, Haizheng; Hall, David J.; Han, Wenlong; Qin, Mingde; Zhao, Chuanzhen; Wang, Meina; She, Zhi-Gang; Cao, Chuanbao; Sailor, Michael J.; Stallcup, William B.; Ruoslahti, Erkki

    2016-01-01

    The rapid development of fluorescence imaging technologies requires concurrent improvements in the performance of fluorescent probes. Quantum dots have been extensively used as an imaging probe in various research areas because of their inherent advantages based on unique optical and electronic properties. However, their clinical translation has been limited by the potential toxicity especially from cadmium. Here, a versatile bioimaging probe is developed by using highly luminescent cadmium-free CuInSe2/ZnS core/shell quantum dots conjugated with CGKRK (Cys–Gly–Lys–Arg–Lys) tumor-targeting peptides. This probe exhibits excellent photostability, reasonably long circulation time, minimal toxicity, and strong tumor-specific homing property. The most important feature of this probe is that it shows distinctive versatility in tumor-targeted multimodal imaging including near-infrared, time-gated, and two-photon imaging in different tumor models. In a glioblastoma mouse model, the targeted probe clearly denotes tumor boundaries and positively labels a population of diffusely infiltrating tumor cells, suggesting its utility in precise tumor detection during surgery. This work lays a foundation for potential clinical translation of the probe.

  2. Targeting tumor perfusion and oxygenation to improve the outcome of anticancer therapy.

    PubMed

    Jordan, Bénédicte F; Sonveaux, Pierre

    2012-01-01

    Radiotherapy and chemotherapy are widespread clinical modalities for cancer treatment. Among other biological influences, hypoxia is a main factor limiting the efficacy of radiotherapy, primarily because oxygen is involved in the stabilization of the DNA damage caused by ionizing radiations. Radiobiological hypoxia is found in regions of rodent and human tumors with a tissue oxygenation level below 10 mmHg at which tumor cells become increasingly resistant to radiation damage. Since hypoxic tumor cells remain clonogenic, their resistance to the treatment strongly influences the therapeutic outcome of radiotherapy. There is therefore an urgent need to identify adjuvant treatment modalities aimed to increase tumor pO(2) at the time of radiotherapy. Since tumor hypoxia fundamentally results from an imbalance between oxygen delivery by poorly efficient blood vessels and oxygen consumption by tumor cells with high metabolic activities, two promising approaches are those targeting vascular reactivity and tumor cell respiration. This review summarizes the current knowledge about the development and use of tumor-selective vasodilators, inhibitors of tumor cell respiration, and drugs and treatments combining both activities in the context of tumor sensitization to X-ray radiotherapy. Tumor-selective vasodilation may also be used to improve the delivery of circulating anticancer agents to tumors. Imaging tumor perfusion and oxygenation is of importance not only for the development and validation of such combination treatments, but also to determine which patients could benefit from the therapy. Numerous techniques have been developed in the preclinical setting. Hence, this review also briefly describes both magnetic resonance and non-magnetic resonance in vivo methods and compares them in terms of sensitivity, quantitative or semi-quantitative properties, temporal, and spatial resolutions, as well as translational aspects. PMID:22661950

  3. Targeting Tumor Perfusion and Oxygenation to Improve the Outcome of Anticancer Therapy1

    PubMed Central

    Jordan, Bénédicte F.; Sonveaux, Pierre

    2012-01-01

    Radiotherapy and chemotherapy are widespread clinical modalities for cancer treatment. Among other biological influences, hypoxia is a main factor limiting the efficacy of radiotherapy, primarily because oxygen is involved in the stabilization of the DNA damage caused by ionizing radiations. Radiobiological hypoxia is found in regions of rodent and human tumors with a tissue oxygenation level below 10 mmHg at which tumor cells become increasingly resistant to radiation damage. Since hypoxic tumor cells remain clonogenic, their resistance to the treatment strongly influences the therapeutic outcome of radiotherapy. There is therefore an urgent need to identify adjuvant treatment modalities aimed to increase tumor pO2 at the time of radiotherapy. Since tumor hypoxia fundamentally results from an imbalance between oxygen delivery by poorly efficient blood vessels and oxygen consumption by tumor cells with high metabolic activities, two promising approaches are those targeting vascular reactivity and tumor cell respiration. This review summarizes the current knowledge about the development and use of tumor-selective vasodilators, inhibitors of tumor cell respiration, and drugs and treatments combining both activities in the context of tumor sensitization to X-ray radiotherapy. Tumor-selective vasodilation may also be used to improve the delivery of circulating anticancer agents to tumors. Imaging tumor perfusion and oxygenation is of importance not only for the development and validation of such combination treatments, but also to determine which patients could benefit from the therapy. Numerous techniques have been developed in the preclinical setting. Hence, this review also briefly describes both magnetic resonance and non-magnetic resonance in vivo methods and compares them in terms of sensitivity, quantitative or semi-quantitative properties, temporal, and spatial resolutions, as well as translational aspects. PMID:22661950

  4. Vivid tumor imaging utilizing liposome-carried bimodal radiotracer.

    PubMed

    Kim, Jonghee; Pandya, Darpan N; Lee, Woonghee; Park, Jang Woo; Kim, Youn Ji; Kwak, Wonjung; Ha, Yeong Su; Chang, Yongmin; An, Gwang Il; Yoo, Jeongsoo

    2014-04-10

    By developing a new bimodal radioactive tracer that emits both luminescence and nuclear signals, a trimodal liposome for optical, nuclear, and magnetic resonance imaging is efficiently prepared. Fast clearance of the radiotracer from reticuloendothelial systems enables vivid tumor imaging with minimum background. PMID:24900846

  5. Tumor hypoxia: a new PET imaging biomarker in clinical oncology.

    PubMed

    Tamaki, Nagara; Hirata, Kenji

    2016-08-01

    Tumor hypoxia is associated with tumor progression and resistance to various treatments. Noninvasive imaging using positron emission tomography (PET) and F-18-labeled fluoromisonidazole (FMISO) was recently introduced in order to define and quantify tumor hypoxia. The FMISO uptake was closely correlated with pimonidazole immunohistochemistry and hypoxia-inducible factor 1 expression in basic studies. Tumor hypoxia in head and neck cancers and other tumors in a clinical setting may also indicate resistance to radiation and/or chemotherapy. Hypoxic imaging may thus play a new and important role for suitable radiation planning, including dose escalation and dose reduction based on the image findings. Such radiation-dose painting based on the findings of hypoxia may require high-performance PET imaging to provide high target-to-background ratio images and an optimal quantitative parameter to define the hypoxic region. A multicenter prospective study using data from a large number of patients is also warranted to test the clinical value of hypoxic imaging. PMID:26577447

  6. PESIN multimerization improves receptor avidities and in vivo tumor targeting properties to GRPR-overexpressing tumors.

    PubMed

    Lindner, Simon; Michler, Christina; Wängler, Björn; Bartenstein, Peter; Fischer, Gabriel; Schirrmacher, Ralf; Wängler, Carmen

    2014-03-19

    The gastrin releasing peptide receptor (GRPR), being overexpressed on several tumor types, represents a promising target for specific noninvasive in vivo tumor imaging using positron emission tomography. Many of the radiolabeled bombesin analogs being applied in tumor imaging, however, suffer from shortcomings such as limited in vivo stability and poor tumor to background ratios. These obstacles can be overcome by peptide multimerization, as this approach results in constructs comprising several copies of the same peptide, thus retaining the ability to specifically bind to the target structure even if one peptide is cleaved. Furthermore, peptide multimers can result in increased binding avidities to the target, which can entail higher absolute tumor uptakes and also tumor to background levels. We therefore synthesized monomers and multimers of the peptide PESIN on dendrimer scaffolds comprising linkers of different lengths. The monomers/multimers were functionalized with the chelator NODAGA, efficiently radiolabeled with (68)Ga and evaluated in vitro regarding their GRPR binding affinity. The results show that shorter distances between the peptide moieties result in substantially higher binding affinities/avidities of the monovalent/multivalent PESIN ligands to the GRPR. Furthermore, the bivalent ligands gave the best results in terms of binding avidity, achieving a 2.5-fold increase in avidity compared to the respective monomer. Moreover, the most potent bivalent ligand showed an about 2-fold higher absolute tumor uptake and twice as high tumor-to-background ratios than the monomeric reference DOTA-PESIN in an initial animal PET study in tumor-bearing mice. Thus, besides high avidities, multivalency also positively influences the in vivo pharmacokinetics of peptide multimers. PMID:24533789

  7. Infrared spectroscopic imaging of kidney tumor tissue

    NASA Astrophysics Data System (ADS)

    Sablinskas, V.; Steiner, G.; Koch, E.; Ceponkus, J.; Pucetaite, M.; Strazdaite, S.; Urboniene, V.; Jankevicius, F.

    2011-02-01

    Infrared spectroscopic imaging of cancerous kidney tissue was performed by means of FTIR microscopy. The spectra of thin tissue cryosections were collected with 64x64 MCT FPA detector and imaging area was increased up to 5.4×5.4 mm by mapping by means of PC controlled x,y stage. Chemical images of the samples were constructed using statistical treatment of the raw spectra. Several unsupervised and supervised statistical methods were used. The imaging results are compared with results of the standard histopathological analysis. It was concluded that application of method of cluster analysis ensures the best contrast of the images. It was found that border between cancerous and normal tissues visible in the infrared spectroscopic image corresponds with the border visible in histopathological image. Closer examination of the infrared spectroscopic image reveals that small domains of cancerous cells are found beyond the border in areas distant from the border up to 3 mm. Such domains are not visible in the histopathological images. The smallest domains found in the infrared images are approx. 60 μm.

  8. Biological basis of tumor imaging with radiolabeled glucose analogs

    SciTech Connect

    Rasey, J.S.; Krohn, K.A.; Nelson, N.; Grunbaum, Z.; Link, J.

    1984-01-01

    Accelerated tumor glycolysis may form the basis for nuclear imaging of tumors with gamma or positron labeled glucose analogs such as F-18 fluorodeoxyglucose (FDG) or C-11 deoxyglucose (DG). FDG may be preferable because it crosses some cell membranes more readily than DG, while the latter is a better substrate for glucose hexokinase, the enzyme which phosphorylates the analog to an intermediate trapped in the cell. C-14-DG and H-3-FDG were compared in biodistribution studies in C3H mice bearing RIF-1 tumors. The two compounds were cleared very similarly from the blood. At 60 min after injection, tumor, brain, and heart concentrated more H-3-FDG than C-14-DG, while liver and lung were equal. These results indicate that the lumped constant will differ for different tissues and/or glucose analogs. Tumor:blood and tumor:liver ratios for H-3-FDG were 14.5 and 7.4 respectively, higher than similar values for C-14-DG: 9.4 and 5.6. Tumor:lung ratios were similar for the two compounds, 2.8 versus 2.3. These factors are critical to imaging primary tumors or metastases in these common target organs. Although F-18-FDG and H-3-FDG are labeled in different positions, the fluorinated and tritiated analogs were taken up and retained similarly in most tissues. Tumors undergoing radiation therapy as well as those previously untreated might be imaged with radiolabeled glucose analogs. Because glycolysis is a radiation resistant cellular process, glucose analog uptake in radiated and control RIF-1 tumors is being compared.

  9. Galactose as Broad Ligand for Multiple Tumor Imaging and Therapy

    PubMed Central

    Ma, Yuxiang; Chen, Haiyan; Su, Shanyuhan; Wang, Tong; Zhang, Congying; Fida, Guissi; Cui, Sisi; Zhao, Juan; Gu, Yueqing

    2015-01-01

    Galactose residues could be specifically recognized by the asialoglycoprotein receptor (ASGPR) which is highly exhibited on liver tissues. However, ASGPR has not been widely investigated on different tumor cell lines except for hepatoma carcinoma cells, which motivates us to investigate the possibility of galactose serving as a board tumor ligand. In this study, a galactose (Gal)-based probe conjugated with fluorescence dye MPA (Gal-MPA) was constructed for the evaluation of tumor affinities/targeted ability on different tumor cell lines. In the vitro cell study, it was indicated that the fluorescence probe Gal-MPA displayed higher cell affinity to tumor cells (HepG2, MCF-7 and A549) than that of the normal liver cells l02. In the vivo dynamic study of Gal-MPA in tumor-bearing mice (HepG2, MCF-7, A549, HCT116, U87, MDA-MB-231 and S180), it was shown that its high tumor targeted ability with the maximal tumor/normal tissue ratio reached up to 6.8. Meanwhile, the fast tumor-targeted ability within 2 hours and long retention on tumor site up to 120 hours were observed. Our results demonstrated that galactose should be a promising broad ligand for multiple tumor imaging and targeted therapy. Subsequently, Gal was covalently conjugated to doxorubicin (DOX) to form prodrug Gal-DOX for tumor targeted therapy. The therapeutic results of Gal-DOX than DOX being better suggested that galactosylated prodrugs might have the prospective potential in tumor targeted therapy. PMID:26078797

  10. Photoacoustic imaging with rotational compounding for improved signal detection

    NASA Astrophysics Data System (ADS)

    Forbrich, A.; Heinmiller, A.; Jose, J.; Needles, A.; Hirson, D.

    2015-03-01

    Photoacoustic microscopy with linear array transducers enables fast two-dimensional, cross-sectional photoacoustic imaging. Unfortunately, most ultrasound transducers are only sensitive to a very narrow angular acceptance range and preferentially detect signals along the main axis of the transducer. This often limits photoacoustic microscopy from detecting blood vessels which can extend in any direction. Rotational compounded photoacoustic imaging is introduced to overcome the angular-dependency of detecting acoustic signals with linear array transducers. An integrate system is designed to control the image acquisition using a linear array transducer, a motorized rotational stage, and a motorized lateral stage. Images acquired at multiple angular positions are combined to form a rotational compounded image. We found that the signal-to-noise ratio improved, while the sidelobe and reverberation artifacts were substantially reduced. Furthermore, the rotational compounded images of excised kidneys and hindlimb tumors of mice showed more structural information compared with any single image collected.

  11. In vivo macroscopic HPD fluorescence reflectance imaging on small animals bearing surface ARO/NPA tumor

    NASA Astrophysics Data System (ADS)

    Autiero, Maddalena; Celentano, Luigi; Laccetti, Paolo; Marotta, Marcello; Mettivier, Giovanni; Montesi, Maria C.; Riccio, Patrizia; Russo, Paolo; Roberti, Giuseppe

    2005-08-01

    Recently multimodal imaging systems have been devised because the combination of different imaging modalities results in the complementarity and integration of the techniques and in a consequent improvement of the diagnostic capabilities of the multimodal system with respect to each separate imaging modality. We developed a simple and reliable HematoPorphyrin (HP) mediated Fluorescence Reflectance Imaging (FRI) system that allows for in vivo real time imaging of surface tumors with a large field of view. The tumor cells are anaplastic human thyroid carcinoma-derived ARO cells, or human papillary thyroid carcinoma-derived NPA cells. Our measurements show that the optical contrast of the tumor region image is increased by a simple digital subtraction of the background fluorescence and that HP fluorescence emissivity of ARO tumors is about 2 times greater than that of NPA tumors, and about 4 times greater than that of healthy tissues. This is also confirmed by spectroscopic measurements on histological sections of tumor and healthy tissues. It was shown also the capability of this system to distinguish the tumor type on the basis of the different intensity of the fluorescence emission, probably related to the malignancy degree. The features of this system are complementary with those ones of a pixel radionuclide detection system, which allows for relatively time expensive, narrow field of view measurements, and applicability to tumors also deeply imbedded in tissues. The fluorescence detection could be used as a large scale and quick analysis tool and could be followed by narrow field, higher resolution radionuclide measurements on previously determined highly fluorescent regions.

  12. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation.

    PubMed

    Unkelbach, Jan; Menze, Bjoern H; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  13. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    NASA Astrophysics Data System (ADS)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most

  14. Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy.

    PubMed

    Chen, Dan; Li, Bowen; Cai, Songhua; Wang, Peng; Peng, Shuwen; Sheng, Yuanzhi; He, Yuanyuan; Gu, Yueqing; Chen, Haiyan

    2016-09-01

    Dual targeting towards both extracellular and intracellular receptors specific to tumor is a significant approach for cancer diagnosis and therapy. In the present study, a novel nano-platform (AuNC-cRGD-Apt) with dual targeting function was initially established by conjugating gold nanocluster (AuNC) with cyclic RGD (cRGD) that is specific to αvβ3integrins over-expressed on the surface of tumor tissues and aptamer AS1411 (Apt) that is of high affinity to nucleolin over-expressed in the cytoplasm and nucleus of tumor cells. Then, AuNC-cRGD-Apt was further functionalized with near infrared (NIR) fluorescence dye (MPA), giving a NIR fluorescent dual-targeting probe AuNC-MPA-cRGD-Apt. AuNC-MPA-cRGD-Apt displays low cytotoxicity and favorable tumor-targeting capability at both in vitro and in vivo level, suggesting its clinical potential for tumor imaging. Additionally, Doxorubicin (DOX), a widely used clinical chemotherapeutic drug that kill cancer cells by intercalating DNA in cellular nucleus, was immobilized onto AuNC-cRGD-Apt forming a pro-drug, AuNC-DOX-cRGD-Apt. The enhanced tumor affinity, deep tumor penetration and improved anti-tumor activity of this pro-drug were demonstrated in different tumor cell lines, tumor spheroid and tumor-bearing mouse models. Results in this study suggest not only the prospect of non-toxic AuNC modified with two targeting ligands for tumor targeted imaging, but also confirm the promising future of dual targeting AuNC as a core for the design of prodrug in the field of cancer therapy. PMID:27236844

  15. Improved scanning laser fundus imaging using polarimetry

    NASA Astrophysics Data System (ADS)

    Bueno, Juan M.; Hunter, Jennifer J.; Cookson, Christopher J.; Kisilak, Marsha L.; Campbell, Melanie C. W.

    2007-05-01

    We present a polarimetric technique to improve fundus images that notably simplifies and extends a previous procedure [Opt. Lett.27, 830 (2002)]. A generator of varying polarization states was incorporated into the illumination path of a confocal scanning laser ophthalmoscope. A series of four images, corresponding to independent incoming polarization states, were recorded. From these images, the spatially resolved elements of the top row of the Mueller matrix were computed. From these elements, images with the highest and lowest quality (according to different image quality metrics) were constructed, some of which provided improved visualization of fundus structures of clinical importance (vessels and optic nerve head). The metric values were better for these constructed images than for the initially recorded images and better than averaged images. Entropy is the metric that is most sensitive to differences in the image quality. Improved visualization of features could aid in the detection, localization, and tracking of ocular disease and may be applicable in other biomedical imaging.

  16. Feasibility of multi-spectral imaging system to provide enhanced demarcation for skin tumor resection

    NASA Astrophysics Data System (ADS)

    de Roode, Rowland; Noordmans, Herke Jan; Verdaasdonk, Rudolf

    2007-02-01

    Invading tumors like basal cell carcinoma have usually no distinct demarcation for the human eye. Therefore, during resection, an additional rim around the tumor is removed. However, extending sprouts can be missed since most lesions are not uniform. To improve the visualization of the tumor demarcation, we developed a multi-spectral imaging system especially adapted for dermatological applications based on tunable liquid crystal spectral tunable filter technology and LED illumination. Enhanced visualization of skin tumor demarcation was achieved using three strategies. The first strategy is based on creating false color images by combining narrow band spectral filtered images by placing them into the red, green and blue image components of a color image at three specific wavelengths. These specific wavelengths were determined using a trial on error tool to achieve the highest contrast between malignant and healthy tissue. The second strategy is to make ratio images of narrow band spectral filtered images at specific wavelengths. A trail on error tool was created which enables the user to try multiple wavelengths to obtain optimal contrast. This method could be applied in realtime. For the third strategy, on pixel spectral segmentation is applied by selecting the pixel spectra in the center of a tumor, surrounding tissue and healthy tissue far away from the tumor. The correlation between these specific spectra and all image pixels is calculated using a fast algorithm. The degree is correlation is graded by color coding and presented in a false color images showing a detailed demarcation of suspicious regions in the tissue. Although this strategy is expected to provide a higher specificity, it takes more time to calculate than the first strategy.

  17. Parametric imaging of tumor perfusion and neovascular morphology using ultrasound

    NASA Astrophysics Data System (ADS)

    Hoyt, Kenneth

    2015-03-01

    A new image processing strategy is detailed for the simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. A technique for locally mapping tumor perfusion parameters using skeletonized neovascular data is also introduced. Simulated images were used to test the neovascular skeletonization technique and variance (error) of relevant parametric estimates. Preliminary DCE-US image datasets were collected in 6 female patients diagnosed with invasive breast cancer and using a Philips iU22 ultrasound system equipped with a L9-3 MHz transducer and Definity contrast agent. Simulation data demonstrates that neovascular morphology parametric estimation is reproducible albeit measurement error can occur at a lower signal-to-noise ratio (SNR). Experimental results indicate the feasibility of our approach to performing both tumor perfusion and neovascular morphology measurements from DCE-US images. Future work will expand on our initial clinical findings and also extent our image processing strategy to 3-dimensional space to allow whole tumor characterization.

  18. Intravital Microscopy for Imaging the Tumor Microenvironment in Live Mice.

    PubMed

    Naumenko, Victor; Jenne, Craig; Mahoney, Douglas J

    2016-01-01

    The development of intravital microscopy has provided unprecedented capacity to study the tumor microenvironment in live mice. The dynamic behavior of cancer, stromal, vascular, and immune cells can be monitored in real time, in situ, in both primary tumors and metastatic lesions, allowing treatment responses to be observed at single cell resolution and therapies tracked in vivo. These features provide a unique opportunity to elucidate the cellular mechanisms underlying the biology and treatment of cancer. We describe here a method for imaging the microenvironment of subcutaneous tumors grown in mice using intravital microscopy. PMID:27581025

  19. CT imaging of ovarian yolk sac tumor with emphasis on differential diagnosis.

    PubMed

    Li, Yang-Kang; Zheng, Yu; Lin, Jian-Bang; Xu, Gui-Xiao; Cai, Ai-Qun; Zhou, Xiu-Guo; Zhang, Guo-Jun

    2015-01-01

    Ovarian yolk sac tumors (YSTs) are rare neoplasms. No radiological study has been done to compare the imaging findings between this type of tumor and other ovarian tumors. Here we analyzed the CT findings of 11 pathologically proven ovarian YSTs and compared their imaging findings with 18 other types of ovarian tumors in the same age range. Patient age, tumor size, tumor shape, ascites and metastasis of two groups did not differ significantly (P > 0.05). A mixed solid-cystic nature, intratumoral hemorrhage, marked enhancement and dilated intratumoral vessel of two groups differed significantly (P < 0.05). The area under the ROC curve of four significant CT features was 0.679, 0.707, 0.705, and 1.000, respectively. Multivariate logistic regression analysis identified two independent signs of YST: intratumoral hemorrhage and marked enhancement. Our results show that certain suggestive CT signs that may be valuable for improving the accuracy of imaging diagnosis of YST and may be helpful in distinguishing YST from other ovarian tumors. PMID:26074455

  20. Longitudinal optical imaging of tumor metabolism and hemodynamics

    NASA Astrophysics Data System (ADS)

    Skala, Melissa C.; Fontanella, Andrew; Lan, Lan; Izatt, Joseph A.; Dewhirst, Mark W.

    2010-01-01

    An important feature of tumor hypoxia is its temporal instability, or ``cycling hypoxia.'' The primary consequence of cycling hypoxia is increased tumor aggressiveness and treatment resistance beyond that of chronic hypoxia. Longitudinal imaging of tumor metabolic demand, hemoglobin oxygen saturation, and blood flow would provide valuable insight into the mechanisms and distribution of cycling hypoxia in tumors. Fluorescence imaging of metabolic demand via the optical redox ratio (fluorescence intensity of FAD/NADH), absorption microscopy of hemoglobin oxygen saturation, and Doppler optical coherence tomography of vessel morphology and blood flow are combined to noninvasively monitor changes in oxygen supply and demand in the mouse dorsal skin fold window chamber tumor model (human squamous cell carcinoma) every 6 h for 36 h. Biomarkers for metabolic demand, blood oxygenation, and blood flow are all found to significantly change with time (p<0.05). These variations in oxygen supply and demand are superimposed on a significant (p<0.05) decline in metabolic demand with distance from the nearest vessel in tumors (this gradient was not observed in normal tissues). Significant (p<0.05), but weak (r<=0.5) correlations are found between the hemoglobin oxygen saturation, blood flow, and redox ratio. These results indicate that cycling hypoxia depends on both oxygen supply and demand, and that noninvasive optical imaging could be a valuable tool to study therapeutic strategies to mitigate cycling hypoxia, thus increasing the effectiveness of radiation and chemotherapy.

  1. MR Molecular Imaging of Tumor Vasculature and Vascular Targets

    PubMed Central

    Pathak, Arvind P.; Penet, Marie-France; Bhujwalla, Zaver M.

    2016-01-01

    Tumor angiogenesis and the ability of cancer cells to induce neovasculature continue to be a fascinating area of research. As the delivery network that provides substrates and nutrients, as well as chemotherapeutic agents to cancer cells, but allows cancer cells to disseminate, the tumor vasculature is richly primed with targets and mechanisms that can be exploited for cancer cure or control. The spatial and temporal heterogeneity of tumor vasculature, and the heterogeneity of response to targeting, make noninvasive imaging essential for understanding the mechanisms of tumor angiogenesis, tracking vascular targeting, and detecting the efficacy of antiangiogenic therapies. With its noninvasive characteristics, exquisite spatial resolution and range of applications, magnetic resonance imaging (MRI) techniques have provided a wealth of functional and molecular information on tumor vasculature in applications spanning from “bench to bedside”. The integration of molecular biology and chemistry to design novel imaging probes ensures the continued evolution of the molecular capabilities of MRI. In this review, we have focused on developments in the characterization of tumor vasculature with functional and molecular MRI. PMID:20807600

  2. Imaging of Brain Tumors With Paramagnetic Vesicles Targeted to Phosphatidylserine

    PubMed Central

    Winter, Patrick M.; Pearce, John; Chu, Zhengtao; McPherson, Christopher M.; Takigiku, Ray; Lee, Jing-Huei; Qi, Xiaoyang

    2014-01-01

    Purpose To investigate paramagnetic saposin C and dioleylphosphatidylserine (SapC-DOPS) vesicles as a targeted contrast agent for imaging phosphatidylserine (PS) expressed by glioblastoma multiforme (GBM) tumors. Materials and Methods Gd-DTPA-BSA/SapC-DOPS vesicles were formulated, and the vesicle diameter and relaxivity were measured. Targeting of Gd-DTPA-BSA/ SapC-DOPS vesicles to tumor cells in vitro and in vivo was compared with nontargeted paramagnetic vesicles (lacking SapC). Mice with GBM brain tumors were imaged at 3, 10, 20, and 24 h postinjection to measure the relaxation rate (R1) in the tumor and the normal brain. Results The mean diameter of vesicles was 175 nm, and the relaxivity at 7 Tesla was 3.32 (s*mM)−1 relative to the gadolinium concentration. Gd-DTPA-BSA/SapC-DOPS vesicles targeted cultured cancer cells, leading to an increased R1 and gadolinium level in the cells. In vivo, Gd-DTPA-BSA/SapC-DOPS vesicles produced a 9% increase in the R1 of GBM brain tumors in mice 10 h postinjection, but only minimal changes (1.2% increase) in the normal brain. Nontargeted paramagnetic vesicles yielded minimal change in the tumor R1 at 10 h postinjection (1.3%). Conclusion These experiments demonstrate that Gd-DTPA-BSA/SapC-DOPS vesicles can selectively target implanted brain tumors in vivo, providing noninvasive mapping of the cancer biomarker PS. PMID:24797437

  3. Intraoperative Imaging of Tumors Using Cerenkov Luminescence Endoscopy: A Feasibility Experimental Study

    PubMed Central

    Liu, Hongguang; Carpenter, Colin M.; Jiang, Han; Pratx, Guillem; Sun, Conroy; Buchin, Michael P.; Gambhir, Sanjiv S.; Xing, Lei; Cheng, Zhen

    2016-01-01

    Cerenkov luminescence imaging (CLI) is an emerging new molecular imaging modality that is relatively inexpensive, easy to use, and has high throughput. CLI can image clinically available PET and SPECT probes using optical instrumentation. Cerenkov luminescence endoscopy (CLE) is one of the most intriguing applications that promise potential clinical translation. We developed a prototype customized fiberscopic Cerenkov imaging system to investigate the potential in guiding minimally invasive surgical resection. Methods All experiments were performed in a dark chamber. Cerenkov luminescence from 18F-FDG samples containing decaying radioactivity was transmitted through an optical fiber bundle and imaged by an intensified charge-coupled device camera. Phantoms filled with 18F-FDG were used to assess the imaging spatial resolution. Finally, mice bearing subcutaneous C6 glioma cells were injected intravenously with 18F-FDG to determine the feasibility of in vivo imaging. The tumor tissues were exposed, and CLI was performed on the mouse before and after surgical removal of the tumor using the fiber-based imaging system and compared with a commercial optical imaging system. Results The sensitivity of this particular setup was approximately 45 kBq (1.21 μCi)/300 μL. The 3 smallest sets of cylindric holes in a commercial SPECT phantom were identifiable via this system, demonstrating that the system has a resolution better than 1.2 mm. Finally, the in vivo tumor imaging study demonstrated the feasibility of using CLI to guide the resection of tumor tissues. Conclusion This proof-of-concept study explored the feasibility of using fiber-based CLE for the detection of tumor tissue in vivo for guided surgery. With further improvements of the imaging sensitivity and spatial resolution of the current system, CLE may have a significant application in the clinical setting in the near future. PMID:22904353

  4. Recent developments in imaging of pancreatic neuroendocrine tumors

    PubMed Central

    Kartalis, Nikolaos; Mucelli, Raffaella Maria Pozzi; Sundin, Anders

    2015-01-01

    Pancreatic neuroendocrine tumors (PNETs) are very rare, accounting for 1-2% of all pancreatic neoplasms. They are classified into functioning and non-functioning and their behavior varies widely from benign to highly malignant. For their investigation, a variety of anatomical and functional imaging methods are available. Anatomical methods include computed tomography (CT), magnetic resonance imaging, and ultrasonography. Functional methods include scintigraphy and positron emission tomography (PET). A combination of anatomical and morphological methods results in the so-called hybrid imaging, such as PET/CT. We herein discuss the currently available imaging modalities for the investigation of PNETs and, more specifically, their applications in tumor detection and staging as well as in choice of therapy, imaging follow up and prediction of response, with emphasis on the recent developments. PMID:25830417

  5. Diagnose human tumors by THz near-field imaging

    NASA Astrophysics Data System (ADS)

    Chen, Hua; Wang, Xiaozhou; Zhao, Tian; Yang, Jinwen

    2014-09-01

    Based on a THz pipe-based near-field imaging system, we demonstrated the capability of THz imaging to diagnose human breast and liver cancers. Through THz near-field mapping of the absorption constants of cancer tissues, the acquired images can not only clearly distinguish cancer from normal tissues fast, automatically, and correctly without pathological H&E staining, but also identify the distribution region of cancer, which matches well with the identification with pathological examination. Due to its capability to perform quantitative analysis, our study indicates the potential of the THz pipe-based near-field imaging for future automation on human tumor pathological examinations and for quick definition of the tumor margins during the surgical procedure such as breast-conserving surgery. With the help of THz imaging, we can expect to economize the use of hospital and human resources.

  6. In situ assessment of tumor vascularity using fluorine NMR imaging.

    PubMed

    Ceckler, T L; Gibson, S L; Hilf, R; Bryant, R G

    1990-03-01

    In situ fluorine NMR imaging has been used to measure vascularity in subcutaneously implanted mammary tumors. Oxyferol, a perfluorinated blood substitute comprised of an emulsion of 25% w/v perfluorotributylamine, was used as a tracer. Following iv administration, this perfluorocarbon emulsion remains primarily in the vasculature during the image acquisition period. The distribution of the PFTA in the 19F NMR image gives a map of tissue regions with intact vascularity. This technique has been used to demonstrate decreased blood flow in necrotic regions of R3230AC mammary tumors in which vasculature had been damaged either as a result of spontaneous necrosis or by photodynamic therapy (PDT). Damage to tumor vascularity following PDT was observed prior to the development of necrosis. PMID:2325542

  7. Automated Quantification of Tumor Viability in a Rabbit Liver Tumor Model after Chemoembolization Using Infrared Imaging.

    PubMed

    D'inca, Hadrien; Namur, Julien; Ghegediban, Saida Homayra; Wassef, Michel; Pascale, Florentina; Laurent, Alexandre; Manfait, Michel

    2015-07-01

    The rabbit VX2 tumor is a fast-growing carcinoma model commonly used to study new therapeutic devices, such as catheter-based therapies for patients with inoperable hepatocellular carcinoma. The evaluation of tumor viability after such locoregional therapies is essential to directing hepatocellular carcinoma management. We used infrared microspectroscopy for the automatic characterization and quantification of the VX2 liver tumor viability after drug-eluting beads transarterial chemoembolization (DEB-TACE). The protocol consisted of K-means clustering followed by principal component analysis (PCA) and linear discriminant analysis (LDA). The K-means clustering was used to classify the spectra from the infrared images of control or treated tumors and to build a database of many tissue spectra. On the basis of this reference library, the PCA-LDA analysis was used to build a predictive model to identify and quantify automatically tumor viability on unknown tissue sections. For the DEB group, the LDA model determined that the surface of tumor necrosis represented 91.6% ± 8.9% (control group: 33.1% ± 19.6%; Mann-Whitney P = 0.0004) and the viable tumor 2.6% ± 4% (control group: 62.2% ± 15.2%; Mann-Whitney P = 0.0004). Tissue quantification measurements correlated well with tumor necrosis (r = 0.827, P < 0.0001) and viable tumor (r = 0.840, P < 0.0001). Infrared imaging and PCA-LDA analysis could be helpful for easily assessing tumor viability. PMID:25979795

  8. Quantification of tumor fluorescence during intraoperative optical cancer imaging.

    PubMed

    Judy, Ryan P; Keating, Jane J; DeJesus, Elizabeth M; Jiang, Jack X; Okusanya, Olugbenga T; Nie, Shuming; Holt, David E; Arlauckas, Sean P; Low, Phillip S; Delikatny, E James; Singhal, Sunil

    2015-01-01

    Intraoperative optical cancer imaging is an emerging technology in which surgeons employ fluorophores to visualize tumors, identify tumor-positive margins and lymph nodes containing metastases. This study compares instrumentation to measure tumor fluorescence. Three imaging systems (Spectropen, Glomax, Flocam) measured and quantified fluorescent signal-to-background ratios (SBR) in vitro, murine xenografts, tissue phantoms and clinically. Evaluation criteria included the detection of small changes in fluorescence, sensitivity of signal detection at increasing depths and practicality of use. In vitro, spectroscopy was superior in detecting incremental differences in fluorescence than luminescence and digital imaging (Ln[SBR] = 6.8 ± 0.6, 2.4 ± 0.3, 2.6 ± 0.1, p = 0.0001). In fluorescent tumor cells, digital imaging measured higher SBRs than luminescence (6.1 ± 0.2 vs. 4.3 ± 0.4, p = 0.001). Spectroscopy was more sensitive than luminometry and digital imaging in identifying murine tumor fluorescence (SBR = 41.7 ± 11.5, 5.1 ± 1.8, 4.1 ± 0.9, p = 0.0001), and more sensitive than digital imaging at detecting fluorescence at increasing depths (SBR = 7.0 ± 3.4 vs. 2.4 ± 0.5, p = 0.03). Lastly, digital imaging was the most practical and least time-consuming. All methods detected incremental differences in fluorescence. Spectroscopy was the most sensitive for small changes in fluorescence. Digital imaging was the most practical considering its wide field of view, background noise filtering capability, and sensitivity to increasing depth. PMID:26563091

  9. Quantification of tumor fluorescence during intraoperative optical cancer imaging

    PubMed Central

    Judy, Ryan P.; Keating, Jane J.; DeJesus, Elizabeth M.; Jiang, Jack X.; Okusanya, Olugbenga T.; Nie, Shuming; Holt, David E.; Arlauckas, Sean P.; Low, Phillip S.; Delikatny, E. James; Singhal, Sunil

    2015-01-01

    Intraoperative optical cancer imaging is an emerging technology in which surgeons employ fluorophores to visualize tumors, identify tumor-positive margins and lymph nodes containing metastases. This study compares instrumentation to measure tumor fluorescence. Three imaging systems (Spectropen, Glomax, Flocam) measured and quantified fluorescent signal-to-background ratios (SBR) in vitro, murine xenografts, tissue phantoms and clinically. Evaluation criteria included the detection of small changes in fluorescence, sensitivity of signal detection at increasing depths and practicality of use. In vitro, spectroscopy was superior in detecting incremental differences in fluorescence than luminescence and digital imaging (Ln[SBR] = 6.8 ± 0.6, 2.4 ± 0.3, 2.6 ± 0.1, p = 0.0001). In fluorescent tumor cells, digital imaging measured higher SBRs than luminescence (6.1 ± 0.2 vs. 4.3 ± 0.4, p = 0.001). Spectroscopy was more sensitive than luminometry and digital imaging in identifying murine tumor fluorescence (SBR = 41.7 ± 11.5, 5.1 ± 1.8, 4.1 ± 0.9, p = 0.0001), and more sensitive than digital imaging at detecting fluorescence at increasing depths (SBR = 7.0 ± 3.4 vs. 2.4 ± 0.5, p = 0.03). Lastly, digital imaging was the most practical and least time-consuming. All methods detected incremental differences in fluorescence. Spectroscopy was the most sensitive for small changes in fluorescence. Digital imaging was the most practical considering its wide field of view, background noise filtering capability, and sensitivity to increasing depth. PMID:26563091

  10. Non-diffeomorphic registration of brain tumor images by simulating tissue loss and tumor growth.

    PubMed

    Zacharaki, Evangelia I; Hogea, Cosmina S; Shen, Dinggang; Biros, George; Davatzikos, Christos

    2009-07-01

    Although a variety of diffeomorphic deformable registration methods exist in the literature, application of these methods in the presence of space-occupying lesions is not straightforward. The motivation of this work is spatial normalization of MR images from patients with brain tumors in a common stereotaxic space, aiming to pool data from different patients into a common space in order to perform group analyses. Additionally, transfer of structural and functional information from neuroanatomical brain atlases into the individual patient's space can be achieved via the inverse mapping, for the purpose of segmenting brains and facilitating surgical or radiotherapy treatment planning. A method that estimates the brain tissue loss and replacement by tumor is applied for achieving equivalent image content between an atlas and a patient's scan, based on a biomechanical model of tumor growth. Automated estimation of the parameters modeling brain tissue loss and displacement is performed via optimization of an objective function reflecting feature-based similarity and elastic stretching energy, which is optimized in parallel via APPSPACK (Asynchronous Parallel Pattern Search). The results of the method, applied to 21 brain tumor patients, indicate that the registration accuracy is relatively high in areas around the tumor, as well as in the healthy portion of the brain. Also, the calculated deformation in the vicinity of the tumor is shown to correlate highly with expert-defined visual scores indicating the tumor mass effect, thereby potentially leading to an objective approach to quantification of mass effect, which is commonly used in diagnosis. PMID:19408350

  11. Indocyanine Green-Loaded Nanoparticles for Image-Guided Tumor Surgery

    PubMed Central

    Hill, Tanner K.; Abdulahad, Asem; Kelkar, Sneha S.; Marini, Frank C.; Long, Timothy E.; Provenzale, James M.; Mohs, Aaron M.

    2015-01-01

    Detecting positive tumor margins and local malignant masses during surgery is critical for long-term patient survival. The use of image-guided surgery for tumor removal, particularly with near-infrared fluorescent imaging, is a potential method to facilitate removing all neoplastic tissue at the surgical site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared dye indocyanine green, termed NanoICG, for improved delivery of the dye to tumors. Self-assembly of the nanoparticles was driven by conjugation of one of three hydrophobic moieties: aminopropyl-1-pyrenebutanamide (PBA), aminopropyl-5β-cholanamide (5βCA), or octadecylamine (ODA). Nanoparticle self-assembly, dye loading, and optical properties were characterized. NanoICG exhibited quenched fluorescence that could be activated by disassembly in a mixed solvent. NanoICG was found to be nontoxic at physiologically relevant concentrations and exposure was not found to inhibit cell growth. Using an MDA-MB-231 tumor xenograft model in mice, strong fluorescence enhancement in tumors was observed with NanoICG using a fluorescence image-guided surgery system and a whole-animal imaging system. Tumor contrast with NanoICG was significantly higher than with ICG alone. PMID:25565445

  12. Iodinated hyaluronic acid oligomer-based nanoassemblies for tumor-targeted drug delivery and cancer imaging.

    PubMed

    Lee, Jae-Young; Chung, Suk-Jae; Cho, Hyun-Jong; Kim, Dae-Duk

    2016-04-01

    Nano-sized self-assemblies based on amphiphilic iodinated hyaluronic acid (HA) were developed for use in cancer diagnosis and therapy. 2,3,5-Triiodobenzoic acid (TIBA) was conjugated to an HA oligomer as a computed tomography (CT) imaging modality and a hydrophobic residue. Nanoassembly based on HA-TIBA was fabricated for tumor-targeted delivery of doxorubicin (DOX). Cellular uptake of DOX from nanoassembly, compared to a DOX solution group, was enhanced via an HA-CD44 receptor interaction, and subsequently, the in vitro antitumor efficacy of DOX-loaded nanoassembly was improved in SCC7 (CD44 receptor positive squamous cell carcinoma) cells. Cy5.5, a near-infrared fluorescence (NIRF) dye, was attached to the HA-TIBA conjugate and the in vivo tumor targetability of HA-TIBA nanoassembly, which is based on the interaction between HA and CD44 receptor, was demonstrated in a NIRF imaging study using an SCC7 tumor-xenografted mouse model. Tumor targeting and cancer diagnosis with HA-TIBA nanoassembly were verified in a CT imaging study using the SCC7 tumor-xenografted mouse model. In addition to efficient cancer diagnosis using NIRF and CT imaging modalities, improved antitumor efficacies were shown. HA and TIBA can be used to produce HA-TIBA nanoassembly that may be a promising theranostic nanosystem for cancers that express the CD44 receptor. PMID:26874284

  13. [Imaging in the diagnosis and the staging of gallbladder tumors].

    PubMed

    Vialle, R; Velasco, S; Milin, S; Bricot, V; Richer, J-P; Levillain, P-M; Tasu, J-P

    2008-11-01

    Most of gallbladder tumors are benign. Adenoma, cholesterol polyps, or adenomyomatosis are most frequently typical on ultrasonographic images. All symptomatic lesions must be considered as indications for surgery. It may be difficult to identify precancerous or malignant lesion. Polyps over 1cm are indication for preventive cholecystectomy. In case of suspicious polyp or suspicious wall thickening, endoscopic ultrasonography can be helpful to evaluate local tumoral spread and eliminate differential diagnosis. Unfortunately, diagnosis of gallbladder cancer is often late, when surgical resection can't be curative. Computed tomography and magnetic resonance imaging examinations are then useful for local and metastatic staging. PMID:18954953

  14. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, Mark M.; Shoup, Timothy

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  15. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, Mark M.; Shoup, Timothy

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  16. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, M.M.; Shoup, T.

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  17. Amino acid analogs for tumor imaging

    DOEpatents

    Goodman, M.M.; Shoup, T.

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  18. Improved delivery of polymer therapeutics to prostate tumors using plasmonic photothermal therapy

    NASA Astrophysics Data System (ADS)

    Gormley, Adam Joseph

    When a patient is presented with locally advanced prostate cancer, it is possible to provide treatment with curative intent. However, once the disease has formed distant metastases, the chances of survival drops precipitously. For this reason, proper management of the disease while it remains localized is of critical importance. Treating these malignant cells with cytotoxic agents is effective at cell killing; however, the nonspecific toxicity profiles of these drugs often limit their use until the disease has progressed and symptom palliation is required. Incorporation of these drugs in nanocarriers such as polymers help target them to tumors with a degree of specificity, though major vascular barriers limit their effective delivery. In this dissertation, it is shown that plasmonic photothermal therapy (PPTT) can be used to help overcome some of these barriers and improve delivery to prostate tumors. First, the concept of using PPTT to improve the delivery of macromolecules to solid tumors was validated. This was done by measuring the tumor uptake of albumin. Next, the concept of targeting gold nanorods (GNRs) directly to the tumor's vasculature to better modulate vascular response to heating was tested. Surface conjugation of cyclic RGD (Arg-Gly-Asp) to GNRs improved their binding and uptake to endothelial cells in vitro, but not in vivo. Nontargeted GNRs and PPTT were then utilized to guide the location of polymer therapeutic delivery to prostate tumors. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, which were designed to be targeted to cells previously exposed to heat shock, were used in this study. Treatment of tumors with PPTT facilitated a burst accumulation of the copolymers over 4 hours, and heat shock targeting to cells allowed them to be retained for an extended period of time. Finally, the tumor localization of the HPMA copolymers following PPTT was evaluated by magnetic resonance imaging (MRI). These results show that PPTT may be a useful tool

  19. Management of Renal Tumors by Image-Guided Radiofrequency Ablation: Experience in 105 Tumors

    SciTech Connect

    Breen, David J. Rutherford, Elizabeth E.; Stedman, Brian; Roy-Choudhury, Shuvro H.; Cast, James E. I.; Hayes, Matthew C.; Smart, Christopher J.

    2007-09-15

    Aims. In this article we present our experience with radiofrequency ablation (RFA) in the treatment of 105 renal tumors. Materials and Methods. RFA was performed on 105 renal tumors in 97 patients, with a mean tumor size of 32 mm (11-68 mm). The mean patient age was 71.7 years (range, 36-89 years). The ablations were carried out under ultrasound (n = 43) or CT (n = 62) guidance. Imaging follow-up was by contrast-enhanced CT within 10 days and then at 6-monthly intervals. Multivariate analysis was performed to determine variables associated with procedural outcome. Results. Eighty-three tumors were completely treated at a single sitting (79%). Twelve of the remaining tumors were successfully re-treated and a clinical decision was made not to re-treat seven patients. A patient with a small residual crescent of tumor is under follow-up and may require further treatment. In another patient, re-treatment was abandoned due to complicating pneumothorax and difficult access. One patient is awaiting further re-treatment. The overall technical success rate was 90.5%. Multivariate analysis revealed tumor size to be the only significant variable affecting procedural outcome. (p = 0.007, Pearson {chi}{sup 2}) Five patients had complications. There have been no local recurrences. Conclusion. Our experience to date suggests that RFA is a safe and effective, minimally invasive treatment for small renal tumors.

  20. Assessment of hepatic VX2 tumors with combined percutaneous transhepatic lymphosonography and contrast-enhanced ultrasonographic imaging

    PubMed Central

    Liu, Cun; Liang, Ping; Wang, Yang; Zhou, Pei; Li, Xin; Han, Zhi-Yu; Liu, Shao-Ping

    2008-01-01

    AIM: To evaluate the feasibility and efficacy of percutaneous transhepatic lymphosonography (PTL) as a novel method for the detection of tumor lymphangiogenesis in hepatic VX2 of rabbits and to evaluate combined PTL and routine contrast-enhanced ultrasonographic imaging for the diagnosis of liver cancer. METHODS: Ten rabbits with VX2 tumor were included in this study. SonoVue (0.1 mL/kg) was injected into each rabbit via an ear vein for contrast-enhanced ultrasonographic imaging, and 0.5 mL SonoVue was injected into the normal liver parenchyma near the VX2 tumor for PTL. Images and/or movie clips were stored for further analysis. RESULTS: Ultrasonographic imaging showed VX2 tumors ranging 5-19 mm in the liver of rabbits. The VX2 tumor was hyperechoic and hypoechoic to liver parenchyma at the early and later phase, respectively. The hepatic lymph vessels were visualized immediately after injection of contrast medium and continuously visualized with SonoVue® during PTL. The boundaries of VX2 tumors were hyperechoic to liver parenchyma and the tumors. There was a significant difference in the values for the boundaries of VX2 tumors after injection compared with the liver normal parenchyma and the tumor parenchyma during PTL. CONCLUSION: PTL is a novel method for the detection of tumor lymphangiogenesis in hepatic VX2 of rabbits. Combined PTL and contrast-enhanced ultrasonographic imaging can improve the diagnosis of liver cancer. PMID:18609718

  1. Doxorubicin loaded silica nanorattles actively seek tumors with improved anti-tumor effects

    NASA Astrophysics Data System (ADS)

    Gao, Fuping; Li, Linlin; Liu, Tianlong; Hao, Nanjing; Liu, Huiyu; Tan, Longfei; Li, Hongbo; Huang, Xinglu; Peng, Bo; Yan, Chuanmiao; Yang, Liuqing; Wu, Xiaoli; Chen, Dong; Tang, Fangqiong

    2012-05-01

    Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX-FA-SNs showed lower cytotoxicity in folate receptor negative normal mouse fibroblast cells (L929 cells) compared with free DOX. In vivo tumor-targeted fluorescence imaging indicated specific tumor targeting and uptake of FA-SNs in nude mice bearing subcutaneous HeLa cell-derived xenograft tumors. In vivo anti-tumor experiments demonstrated that DOX-FA-SNs (10 mg kg-1 of DOX) significantly regressed the tumor growth and reduced toxicity compared with free DOX. These results have great significance in developing and optimizing SNs as effective intracellular delivery and specific tumor targeting vehicles.Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX

  2. Noninvasive tumor oxygen imaging by photoacoustic lifetime imaging integrated with photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Shao, Qi; Biel, Merrill A.; Ashkenazi, Shai

    2014-03-01

    Oxygen plays a major role in cancer biology and tumor progression. In PDT, the reduction in efficacy is directly related to lack of oxygen because its molecular mechanism relies on oxygen as an energy mediator. Measuring tumor oxygenation can provide physicians with better diagnosis and optimization of treatment plans. However, clinical tools for directly assessing tissue oxygenation are limited. The gold standard is oxygen needle electrode, which is invasive and measures oxygen level at a single location. We present our work on developing a combined treatment-imaging modality that integrates PDT and photoacoustic oxygen imaging. We propose a system designed for clinical treatments of cancer of the oral cavity. Tissue oxygen imaging is performed by applying Photoacoustic Lifetime Imaging (PALI). This technology relies on photoacoustic probing of oxygen-dependent excitation lifetime of Methylene Blue. The dye is excited by the same wavelength of illumination source for PDT. Once excited, the population of photosensitizer molecules at triplet state has a lifetime depending on the oxygen level. The transition from excited triplet state to ground state can be probe by another laser, which generate photoacoustic signal that is used to map the lifetime. The lifetime map is then converted to pO2 distribution. We expect that PDT efficacy can be improved by applying PALI imaging feedback in real-time to determine, and individually optimize, O2-enriched gas breathing parameters and PDT light-dose during treatment. Successful implementation of PALI in PDT can also drive its application in guiding other cancer treatments that are affected by hypoxia.

  3. In Vivo Fluorescence Reflectance Imaging with Subcutaneous Mouse Tumor Models.

    PubMed

    Cao, Jie; Zhou, Mingzhou

    2016-01-01

    Optical imaging is undoubtedly one of the most versatile and widely used imaging techniques in both research and clinical practice. Among optical imaging technologies, fluorescence imaging is the most popularly used and has become an essential tool in biomedical science. A key component of fluorescence imaging is fluorescence-producing reporters, including fluorescent dyes and conjugates, as well as fluorescent proteins. For in vivo imaging applications, fluorophores with long emission at the near-infrared (NIR) region are generally preferred to overcome the photon attenuation in living tissue. Here, we describe the in vivo fluorescence imaging of an integrin αυβ3 targeted NIR fluorescent probe (cRGD-ICG-Der-02) using subcutaneous mouse tumor models. PMID:27283414

  4. Harmonic Motion Microwave Doppler Imaging method for breast tumor detection.

    PubMed

    Top, Can Barıs; Tafreshi, Azadeh Kamali; Gençer, Nevzat G

    2014-01-01

    Harmonic Motion Microwave Doppler Imaging (HMMDI) method is recently proposed as a non-invasive hybrid breast imaging technique for tumor detection. The acquired data depend on acoustic, elastic and electromagnetic properties of the tissue. The potential of the method is analyzed with simulation studies and phantom experiments. In this paper, the results of these studies are summarized. It is shown that HMMDI method has a potential to detect malignancies inside fibro-glandular tissue. PMID:25571382

  5. Brain tumor segmentation in MR slices using improved GrowCut algorithm

    NASA Astrophysics Data System (ADS)

    Ji, Chunhong; Yu, Jinhua; Wang, Yuanyuan; Chen, Liang; Shi, Zhifeng; Mao, Ying

    2015-12-01

    The detection of brain tumor from MR images is very significant for medical diagnosis and treatment. However, the existing methods are mostly based on manual or semiautomatic segmentation which are awkward when dealing with a large amount of MR slices. In this paper, a new fully automatic method for the segmentation of brain tumors in MR slices is presented. Based on the hypothesis of the symmetric brain structure, the method improves the interactive GrowCut algorithm by further using the bounding box algorithm in the pre-processing step. More importantly, local reflectional symmetry is used to make up the deficiency of the bounding box method. After segmentation, 3D tumor image is reconstructed. We evaluate the accuracy of the proposed method on MR slices with synthetic tumors and actual clinical MR images. Result of the proposed method is compared with the actual position of simulated 3D tumor qualitatively and quantitatively. In addition, our automatic method produces equivalent performance as manual segmentation and the interactive GrowCut with manual interference while providing fully automatic segmentation.

  6. Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

    PubMed

    Uthaman, Saji; Bom, Joon-Suk; Kim, Hyeon Sik; John, Johnson V; Bom, Hee-Seung; Kim, Seon-Jong; Min, Jung-Joon; Kim, Il; Park, In-Kyu

    2016-05-01

    Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 825-834, 2016. PMID:26743660

  7. Novel Approaches to Imaging Tumor Metabolism

    PubMed Central

    Tee, Sui-Seng; Keshari, Kayvan R.

    2015-01-01

    The field of metabolism research has made a dramatic resurgence in recent years, fueled by a newfound appreciation of the interactions between metabolites and phenotype. Metabolic substrates and their products can be biomarkers of a wide range of pathologies, including cancer, but our understanding of their in vivo interactions and pathways has been hindered by the robustness of non-invasive imaging approaches. The last 3 decades have been flushed with the development of new techniques for the study of metabolism in vivo. These methods include nuclear based, predominantly positron emission tomography (PET) and magnetic resonance imaging (MRI), many of which have been translated to the clinic. The purpose of this review is to introduce both long standing imaging strategies as well as novel approaches to the study of perturbed metabolic pathways in the setting of carcinogenesis. This will involve descriptions of nuclear probes labeled with 11C and 18F as well 13C for study using hyperpolarized MRI. Highlighting both advantages and disadvantages of each approach, the aim of this summary is to provide the reader with a framework for interrogation of metabolic aberrations in their system of interest. PMID:26049695

  8. Targeting Artificial Tumor Stromal Targets for Molecular Imaging of Tumor Vascular Hypoxia

    PubMed Central

    Koonce, Nathan A.; Levy, Joseph; Hardee, Matthew E.; Jamshidi-Parsian, Azemat; Vang, Kieng B.; Sharma, Sunil; Raleigh, James A.; Dings, Ruud P. M.; Griffin, Robert J.

    2015-01-01

    Developed and tested for many years, a variety of tumor hypoxia detection methods have been inconsistent in their ability to predict treatment outcomes or monitor treatment efficacy, limiting their present prognostic capability. These variable results might stem from the fact that these approaches are based on inherently wide-ranging global tumor oxygenation levels based on uncertain influences of necrotic regions present in most solid tumors. Here, we have developed a novel non-invasive and specific method for tumor vessel hypoxia detection, as hypoxemia (vascular hypoxia) has been implicated as a key driver of malignant progression, therapy resistance and metastasis. This method is based on high-frequency ultrasound imaging of α-pimonidazole targeted-microbubbles to the exogenously administered hypoxia marker pimonidazole. The degree of tumor vessel hypoxia was assessed in three mouse models of mammary gland carcinoma (4T1, SCK and MMTV-Wnt-1) and amassed up to 20% of the tumor vasculature. In the 4T1 mammary gland carcinoma model, the signal strength of α-pimonidazole targeted-microbubbles was on average 8-fold fold higher in tumors of pimonidazole-injected mice than in non-pimonidazole injected tumor bearing mice or non-targeted microbubbles in pimonidazole-injected tumor bearing mice. Overall, this provides proof of principle for generating and targeting artificial antigens able to be ‘created’ on-demand under tumor specific microenvironmental conditions, providing translational diagnostic, therapeutic and treatment planning potential in cancer and other hypoxia-associated diseases or conditions. PMID:26308944

  9. Molecular imaging of tumor microenvironment: challenges and perspectives.

    PubMed

    Del Vecchio, S; Zannetti, A; Iommelli, F; Lettieri, A; Brunetti, A; Salvatore, M

    2010-06-01

    Tumor microenvironment consists of a number of components including host resident stromal cells, infiltrating immune cells and extracellular matrix. The architecture surrounding tumor cells is not static but is subjected to a continuous remodeling in response to the dynamic interplay between tumor and stromal cells and to the production of extracellular proteases. In addition all these microenvironmental components along with cancer cells are exposed to abnormal physiologic conditions such as hypoxia and acidic extracellular pH that may induce both adaptive and constitutive changes in cancer and stromal cells. In this review, we will primarily focus on the possibility to visualize in vivo tumor microenvironment components and conditions as well as interactions with cancer cells. The major goal is to highlight the difficulties and the opportunities of this approach and how each imaging technology helps to overcome specific challenge. PMID:20639812

  10. Multiresponse imaging system design for improved resolution

    NASA Technical Reports Server (NTRS)

    Alter-Gartenberg, Rachel; Fales, Carl L.; Huck, Friedrich O.; Rahman, Zia-Ur; Reichenbach, Stephen E.

    1991-01-01

    Multiresponse imaging is a process that acquires A images, each with a different optical response, and reassembles them into a single image with an improved resolution that can approach 1/sq rt A times the photodetector-array sampling lattice. Our goals are to optimize the performance of this process in terms of the resolution and fidelity of the restored image and to assess the amount of information required to do so. The theoretical approach is based on the extension of both image restoration and rate-distortion theories from their traditional realm of signal processing to image processing which includes image gathering and display.

  11. Molecular breast imaging: advantages and limitations of a scintimammographic technique in patients with small breast tumors.

    PubMed

    O'Connor, Michael K; Phillips, Stephen W; Hruska, Carrie B; Rhodes, Deborah J; Collins, Douglas A

    2007-01-01

    Preliminary studies from our laboratory showed that molecular breast imaging (MBI) can reliably detect tumors <2 cm in diameter. This study extends our work to a larger patient population and examines the technical factors that influence the ability of MBI to detect small breast tumors. Following injection of 740 MBq Tc-99m sestamibi, MBI was performed on 100 patients scheduled for biopsy of a lesion suspicious for malignancy that measured <2 cm on mammography or sonography. Using a small field of view gamma camera, patients were imaged in the standard mammographic views using light pain-free compression. Subjective discomfort, breast thickness, the amount of breast tissue in the detector field of view, and breast counts per unit area were measured and recorded. Follow-up was obtained in 99 patients; 53 patients had 67 malignant tumors confirmed at surgery. Of these, 57 of 67 were detected by MBI (sensitivity 85%). Sensitivity was 29%, 86%, and 97% for tumors <5, 6-10, and > or =11 mm in diameter, respectively. In seven patients, MBI identified eight additional mammographically occult tumors. Of 47 patients with no evidence of cancer at biopsy or surgery, there were 36 true negative and 11 false positive scans on MBI. MBI has potential for the regular detection of malignant breast tumors less than 2 cm in diameter. Work in progress to optimize the imaging parameters and technique may further improve sensitivity and specificity. PMID:17214787

  12. Folate-modified gold nanoclusters as near-infrared fluorescent probes for tumor imaging and therapy.

    PubMed

    Chen, Haiyan; Li, Shulan; Li, Bowen; Ren, Xueyan; Li, Shengnan; Mahounga, Didel M; Cui, Sisi; Gu, Yueqing; Achilefu, Samuel

    2012-09-28

    Ultra-small gold nanoclusters (Au NCs) are highly promising materials for tumor imaging and therapy because of their low toxicity, intrinsic fluorescence, and the availability of multifunctional groups for covalent linkage of diverse bioactive molecules. Au NCs stabilized by bovine serum albumin (BSA) were prepared via an improved "green" synthetic routine. To ameliorate the selective affinity of Au NCs for high folate receptor (FR) expressing tumors, folic acid (FA) was immobilized on the surface of Au NCs. Subsequently, a near-infrared (NIR) fluorescent dye MPA was conjugated with Au-FA NCs for in vitro and in vivo fluorescence imaging. Similarly, Doxorubicin (DOX), a widely used clinical anticancer drug, was also conjugated to the folate-modified Au NCs to form a prodrug (Au-FA-DOX). Cellular and in vivo acute toxicity studies demonstrated the low toxicity of the Au-FA-MPA to normal cells and tissues. Additionally, in vitro and in vivo study of the dynamic behavior and targeting ability of Au-FA-MPA to different tumors validated the high selective affinity of Au-FA-MPA to FR positive tumors. With regard to the Au-FA-DOX, high anti-tumor activity was displayed by this pro-drug due to the FR mediated uptake. Herein, all of the results supported the potential of using ligand-modified Au NCs for tumor imaging and targeted therapy. PMID:22930451

  13. Framework for hyperspectral image processing and quantification for cancer detection during animal tumor surgery.

    PubMed

    Lu, Guolan; Wang, Dongsheng; Qin, Xulei; Halig, Luma; Muller, Susan; Zhang, Hongzheng; Chen, Amy; Pogue, Brian W; Chen, Zhuo Georgia; Fei, Baowei

    2015-01-01

    Hyperspectral imaging (HSI) is an imaging modality that holds strong potential for rapid cancer detection during image-guided surgery. But the data from HSI often needs to be processed appropriately in order to extract the maximum useful information that differentiates cancer from normal tissue. We proposed a framework for hyperspectral image processing and quantification, which includes a set of steps including image preprocessing, glare removal, feature extraction, and ultimately image classification. The framework has been tested on images from mice with head and neck cancer, using spectra from 450- to 900-nm wavelength. The image analysis computed Fourier coefficients, normalized reflectance, mean, and spectral derivatives for improved accuracy. The experimental results demonstrated the feasibility of the hyperspectral image processing and quantification framework for cancer detection during animal tumor surgery, in a challenging setting where sensitivity can be low due to a modest number of features present, but potential for fast image classification can be high. This HSI approach may have potential application in tumor margin assessment during image-guided surgery, where speed of assessment may be the dominant factor. PMID:26720879

  14. Framework for hyperspectral image processing and quantification for cancer detection during animal tumor surgery

    NASA Astrophysics Data System (ADS)

    Lu, Guolan; Wang, Dongsheng; Qin, Xulei; Halig, Luma; Muller, Susan; Zhang, Hongzheng; Chen, Amy; Pogue, Brian W.; Chen, Zhuo Georgia; Fei, Baowei

    2015-12-01

    Hyperspectral imaging (HSI) is an imaging modality that holds strong potential for rapid cancer detection during image-guided surgery. But the data from HSI often needs to be processed appropriately in order to extract the maximum useful information that differentiates cancer from normal tissue. We proposed a framework for hyperspectral image processing and quantification, which includes a set of steps including image preprocessing, glare removal, feature extraction, and ultimately image classification. The framework has been tested on images from mice with head and neck cancer, using spectra from 450- to 900-nm wavelength. The image analysis computed Fourier coefficients, normalized reflectance, mean, and spectral derivatives for improved accuracy. The experimental results demonstrated the feasibility of the hyperspectral image processing and quantification framework for cancer detection during animal tumor surgery, in a challenging setting where sensitivity can be low due to a modest number of features present, but potential for fast image classification can be high. This HSI approach may have potential application in tumor margin assessment during image-guided surgery, where speed of assessment may be the dominant factor.

  15. Extragastrointestinal stromal tumors: Computed tomography and magnetic resonance imaging findings

    PubMed Central

    ZHU, JINGQI; YANG, ZHANGWEI; TANG, GUANGYU; WANG, ZHONGQIU

    2015-01-01

    Extragastrointestinal stromal tumors (EGISTs) are rare mesenchymal tumors that originate outside the gastrointestinal tract. The aim of the present study was to investigate the computed tomography (CT) and magnetic resonance imaging (MRI) features of EGISTs and analyze the correlations between radiological findings and pathological features. CT and MRI images of 24 patients with EGISTs were reviewed retrospectively. Patient demographics and tumor characteristics, including localization, size, contours, borders, cystic-necrotic components, calcification, hemorrhage, tumor vessels, attenuation and intensity, degree and pattern of enhancement, ascites, tumor invasion, lymphadenopathy and distant metastasis were recorded. Statistical analyses to compare the radiological characteristics of low- and high-grade EGISTs were performed with χ2 or Fisher’s exact tests. The mean patient age at the time of presentation was 53 years. A total of 24 EGISTs were detected, originating in the omentum (n=4), mesentery (n=19) and retroperitoneum (n=1), respectively. The EGISTs displayed a predominantly spindle cell subtype (87.5%; 21/24). The majority of the EGISTs appeared as large (>10 cm; 70.8%; 17/24), round or oval (66.7%; 16/24), cystic-solid (87.5%; 21/24) and ill-defined (66.7%; 16/24) soft-tissue masses. The EGISTs were hypodense (69.6%; 16/23) or isodense (30.4%; 7/23) on CT images, hypointense (50%; 3/6), isointense (33.3%; 2/6) or hyperintense (16.7%; 1/6) on T1-weighted imaging (T1WI), and hyperintense on T2WI (100%; 6/6) and diffusion-WI (DWI; 100%; 6/6). A total of 54.2% (13/24) of the EGISTs displayed tumor vessels. Overall, 95.8% (23/24) of the masses showed marked enhancement and 87.5% (21/24) demonstrated heterogeneous enhancement. Calcification, hemorrhage, ascites and lymphadenopathy were rare characteristics in the EGISTs. Distant metastases were present in 10 patients (41.7%). The size, borders, tumor vessels and distant metastasis correlated with high

  16. The impact of tumor motion upon CT image integrity and target delineation

    SciTech Connect

    Gagne, Isabelle M.; Robinson, Don M.

    2004-12-01

    Accurate planning target volume delineation is vital to the success of conformal radiation techniques such as standard three-dimensional conformal radiotherapy and intensity modulated radiation therapy. With the exception of breath-hold schemes, all current approaches acquire images while the tumor is nonstationary and, as such, are subject to the presence of motion artifacts. In lung cancer sites where tumor mobility can be significant, the detrimental effect of these motion-induced distortions on image quality and subsequently target volume delineation cannot be ignored in the pursuit of improved treatment outcomes. To investigate the fundamental nature and functional dependence of computed tomography (CT) artifacts associated with lung tumor motion, and the implications for tumor delineation, a filtered backprojection algorithm was developed in MATLAB to generate transverse CT simulation images. In addition, a three-dimensional phantom capable of mimicking the essential motions of lung tumors was constructed for experimental verification. Results show that the spatial extent of a mobile object is distorted from its true shape and location and does not accurately reflect the volume occupied during the extent of motion captured. The presence of motion also negatively impacts image intensity (density) integrity rendering accurate volume delineation highly problematic and calling into question the use of such data in CT-based heterogeneity correction algorithms for dosimetric calculation.

  17. Target Coverage in Image-Guided Stereotactic Body Radiotherapy of Liver Tumors

    SciTech Connect

    Wunderink, Wouter . E-mail: w.wunderink@erasmusmc.nl; Romero, Alejandra Mendez; Osorio, Eliana M. Vasquez; Boer, Hans C.J. de; Brandwijk, Rene P.; Levendag, Peter C.; Heijmen, Ben

    2007-05-01

    Purpose: To determine the effect of image-guided procedures (with computed tomography [CT] and electronic portal images before each treatment fraction) on target coverage in stereotactic body radiotherapy for liver patients using a stereotactic body frame (SBF) and abdominal compression. CT guidance was used to correct for day-to-day variations in the tumor's mean position in the SBF. Methods and Materials: By retrospectively evaluating 57 treatment sessions, tumor coverage, as obtained with the clinically applied CT-guided protocol, was compared with that of alternative procedures. The internal target volume-plus (ITV{sup +}) was introduced to explicitly include uncertainties in tumor delineations resulting from CT-imaging artifacts caused by residual respiratory motion. Tumor coverage was defined as the volume overlap of the ITV{sup +}, derived from a tumor delineated in a treatment CT scan, and the planning target volume. Patient stability in the SBF, after acquisition of the treatment CT scan, was evaluated by measuring the displacement of the bony anatomy in the electronic portal images relative to CT. Results: Application of our clinical protocol (with setup corrections following from manual measurements of the distances between the contours of the planning target volume and the daily clinical target volume in three orthogonal planes, multiple two-dimensional) increased the frequency of nearly full ({>=}99%) ITV{sup +} coverage to 77% compared with 63% without setup correction. An automated three-dimensional method further improved the frequency to 96%. Patient displacements in the SBF were generally small ({<=}2 mm, 1 standard deviation), but large craniocaudal displacements (maximal 7.2 mm) were occasionally observed. Conclusion: Daily, CT-assisted patient setup may substantially improve tumor coverage, especially with the automated three-dimensional procedure. In the present treatment design, patient stability in the SBF should be verified with portal

  18. Development of image-processing software for automatic segmentation of brain tumors in MR images

    PubMed Central

    Vijayakumar, C.; Gharpure, Damayanti Chandrashekhar

    2011-01-01

    Most of the commercially available software for brain tumor segmentation have limited functionality and frequently lack the careful validation that is required for clinical studies. We have developed an image-analysis software package called ‘Prometheus,’ which performs neural system–based segmentation operations on MR images using pre-trained information. The software also has the capability to improve its segmentation performance by using the training module of the neural system. The aim of this article is to present the design and modules of this software. The segmentation module of Prometheus can be used primarily for image analysis in MR images. Prometheus was validated against manual segmentation by a radiologist and its mean sensitivity and specificity was found to be 85.71±4.89% and 93.2±2.87%, respectively. Similarly, the mean segmentation accuracy and mean correspondence ratio was found to be 92.35±3.37% and 0.78±0.046, respectively. PMID:21897560

  19. Knowledge-based image processing for proton therapy planning of ocular tumors

    NASA Astrophysics Data System (ADS)

    Noeh, Sebastian; Haarbeck, Klaus; Bornfeld, Norbert; Tolxdorff, Thomas

    1998-06-01

    Our project is concerned with the improvement of radiation treatment procedures for ocular tumors. In this context the application of proton beams offers new possibilities to considerably enhance precision and reliability of current radiation treatment systems. A precise model of the patient's eye and the tumor is essential for determining the necessary treatment plan. Current treatment systems base their irradiation plan calculations mainly on schematic eye models (e.g., Gullstrand's schematic eye). The adjustment of the model to the patient's anatomy is done by distorting the model according to information from ultrasound and/or CT images. In our project a precise model of the orbita is determined from CT, high resolution MRT, ultrasound (A-mode depth images and/or 2D B-mode images) and photographs of the fundus. The results from various segmentation and image analysis steps performed on all the data are combined to achieve an eye model of improved precision. By using a proton cannon for the therapy execution, the high precision of the model can be exploited, thus achieving a basic improvement of the therapy. Control over the destruction of the tumor can be increased by maximizing the dose distributions within the target volume keeping the damage in the surrounding tissue to a minimum. This article is concerned with the image processing to generate an eye model on which treatment planning is based.

  20. Angle correction for small animal tumor imaging with spatial frequency domain imaging (SFDI)

    PubMed Central

    Zhao, Yanyu; Tabassum, Syeda; Piracha, Shaheer; Nandhu, Mohan Sobhana; Viapiano, Mariano; Roblyer, Darren

    2016-01-01

    Spatial frequency domain imaging (SFDI) is a widefield imaging technique that allows for the quantitative extraction of tissue optical properties. SFDI is currently being explored for small animal tumor imaging, but severe imaging artifacts occur for highly curved surfaces (e.g. the tumor edge). We propose a modified Lambertian angle correction, adapted from the Minnaert correction method for satellite imagery, to account for tissue surface angles up to 75°. The method was tested in a hemisphere phantom study as well as a small animal tumor model. The proposed method reduced µa and µs` extraction errors by an average of 64% and 16% respectively compared to performing no angle correction, and provided more physiologically agreeable optical property and chromophore values on tumors. PMID:27375952

  1. Long-Lasting and Efficient Tumor Imaging Using a High Relaxivity Polysaccharide Nanogel Magnetic Resonance Imaging Contrast Agent.

    PubMed

    Chan, Minnie; Lux, Jacques; Nishimura, Tomoki; Akiyoshi, Kazunari; Almutairi, Adah

    2015-09-14

    Clinically approved small-molecule magnetic resonance imaging (MRI) contrast agents are all rapidly cleared from the body and offer weak signal enhancement. To avoid repeated administration of contrast agent and improve signal-to-noise ratios, agents with stronger signal enhancement and better retention in tumors are needed. Therefore, we focused on hydrogels because of their excellent water accessibility and biodegradability. Gadolinium (Gd)-chelating cross-linkers were incorporated into self-assembled pullulan nanogels to both impart magnetic properties and to stabilize this material that has been extensively studied for medical applications. We show that these Gd-chelating pullulan nanogels (Gd-CHPOA) have the highest reported relaxivity for any hydrogel-based particles and accumulate in the 4T1 tumors in mice at high levels 4 h after injection. This combination offers high signal enhancement and lasts up to 7 days to delineate the tumor clearly for longer imaging time scales. Importantly, this long-term accumulation does not cause any damage or toxicity in major organs up to three months after injection. Our work highlights the clinical potential of Gd-CHPOA as a tumor-imaging MRI contrast agent, permitting tumor identification and assessment with a high signal-to-background ratio. PMID:26278775

  2. Bispecific Antibody Pretargeting for Improving Cancer Imaging and Therapy

    SciTech Connect

    Sharkey, Robert M.

    2005-02-04

    The main objective of this project was to evaluate pretargeting systems that use a bispecific antibody (bsMAb) to improve the detection and treatment of cancer. A bsMAb has specificity to a tumor antigen, which is used to bind the tumor, while the other specificity is to a peptide that can be radiolabeled. Pretargeting is the process by which the unlabeled bsMAb is given first, and after a sufficient time (1-2 days) is given for it to localize in the tumor and clear from the blood, a small molecular weight radiolabeled peptide is given. According to a dynamic imaging study using a 99mTc-labeled peptide, the radiolabeled peptide localizes in the tumor in less than 1 hour, with > 80% of it clearing from the blood and body within this same time. Tumor/nontumor targeting ratios that are nearly 50 times better than that with a directly radiolabeled Fab fragment have been observed (Sharkey et al., ''Signal amplification in molecular imaging by a multivalent bispecific nanobody'' submitted). The bsMAbs used in this project have been composed of 3 antibodies that will target antigens found in colorectal and pancreatic cancers (CEA, CSAp, and MUC1). For the ''peptide binding moiety'' of the bsMAb, we initially examined an antibody directed to DOTA, but subsequently focused on another antibody directed against a novel compound, HSG (histamine-succinyl-glycine).

  3. Long circulating reduced graphene oxide-iron oxide nanoparticles for efficient tumor targeting and multimodality imaging.

    PubMed

    Xu, Cheng; Shi, Sixiang; Feng, Liangzhu; Chen, Feng; Graves, Stephen A; Ehlerding, Emily B; Goel, Shreya; Sun, Haiyan; England, Christopher G; Nickles, Robert J; Liu, Zhuang; Wang, Taihong; Cai, Weibo

    2016-07-01

    Polyethylene glycol (PEG) surface modification is one of the most widely used approaches to improve the solubility of inorganic nanoparticles, prevent their aggregation and prolong their in vivo blood circulation half-life. Herein, we developed double-PEGylated biocompatible reduced graphene oxide nanosheets anchored with iron oxide nanoparticles (RGO-IONP-(1st)PEG-(2nd)PEG). The nanoconjugates exhibited a prolonged blood circulation half-life (∼27.7 h) and remarkable tumor accumulation (>11 %ID g(-1)) via an enhanced permeability and retention (EPR) effect. Due to the strong near-infrared absorbance and superparamagnetism of RGO-IONP-(1st)PEG-(2nd)PEG, multimodality imaging combining positron emission tomography (PET) imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging was successfully achieved. The promising results suggest the great potential of these nanoconjugates for multi-dimensional and more accurate tumor diagnosis and therapy in the future. PMID:27109431

  4. Long circulating reduced graphene oxide-iron oxide nanoparticles for efficient tumor targeting and multimodality imaging

    NASA Astrophysics Data System (ADS)

    Xu, Cheng; Shi, Sixiang; Feng, Liangzhu; Chen, Feng; Graves, Stephen A.; Ehlerding, Emily B.; Goel, Shreya; Sun, Haiyan; England, Christopher G.; Nickles, Robert J.; Liu, Zhuang; Wang, Taihong; Cai, Weibo

    2016-06-01

    Polyethylene glycol (PEG) surface modification is one of the most widely used approaches to improve the solubility of inorganic nanoparticles, prevent their aggregation and prolong their in vivo blood circulation half-life. Herein, we developed double-PEGylated biocompatible reduced graphene oxide nanosheets anchored with iron oxide nanoparticles (RGO-IONP-1stPEG-2ndPEG). The nanoconjugates exhibited a prolonged blood circulation half-life (~27.7 h) and remarkable tumor accumulation (>11 %ID g-1) via an enhanced permeability and retention (EPR) effect. Due to the strong near-infrared absorbance and superparamagnetism of RGO-IONP-1stPEG-2ndPEG, multimodality imaging combining positron emission tomography (PET) imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging was successfully achieved. The promising results suggest the great potential of these nanoconjugates for multi-dimensional and more accurate tumor diagnosis and therapy in the future.

  5. Towards automatic determination of total tumor burden from PET images

    NASA Astrophysics Data System (ADS)

    Renisch, Steffen; Opfer, Roland; Wiemker, Rafael

    2010-03-01

    Quantification of potentially cancerous lesions from imaging modalities, most prominently from CT or PET images, plays a crucial role both in diagnosing and staging of cancer as well as in the assessment of the response of a cancer to a therapy, e.g. for lymphoma or lung cancer. For PET imaging, several quantifications which might bear great discriminating potential (e.g. total tumor burden or total tumor glycolysis) involve the segmentation of the entirety of all of the cancerous lesions. However, this particular task of segmenting the entirety of all cancerous lesions might be very tedious if it has to be done manually, in particular if the disease is scattered or metastasized and thus consists of numerous foci; this is one of the reasons why only few clinical studies on those quantifications are available. In this work, we investigate a way to aid the easy determination of the entirety of cancerous lesions in a PET image of a human. The approach is designed to detect all hot spots within a PET image and rank their probability of being a cancerous lesion. The basis of this component is a modified watershed algorithm; the ranking is performed on a combination of several, primarily morphological measures derived from the individual basins. This component is embedded in a software suite to assess response to a therapy based on PET images. As a preprocessing step, potential lesions are segmented and indicated to the user, who can select the foci which constitute the tumor and discard the false positives. This procedure substantially simplifies the segmentation of the entire tumor burden of a patient. This approach of semi-automatic hot spot detection is evaluated on 17 clinical datasets.

  6. Optical imaging predicts tumor response to anti-EGFR therapy

    PubMed Central

    Helman, Emily E; Newman, J Robert; Dean, Nichole R; Zhang, Wenyue; Zinn, Kurt R

    2010-01-01

    To evaluate cetuximab treatment in head and neck squamous cell carcinoma xenografts and cell lines, we investigated a preclinical model of head and neck squamous cell carcinoma. Head and neck squamous cell carcinoma cell lines SCC-1, FaDu, CAL27, UM-SCC-5 and UM-SCC-22A were used to generate subcutaneous flank xenografts in SCID mice. Mice were divided into control and cetuximab treatment groups, mice in the latter group received 250 µg cetuximab once weekly for four weeks. After completion of therapy, SCC-1 (p < 0.001), UM-SCC-5 (p < 0.001), UM-SCC-22A (p = 0.016) and FaDu (p = 0.007) tumors were significantly smaller than control, while CAL27 tumors were not different from controls (p = 0.90). Mice were systemically injected with 50 µg of the Cy5.5-cetuximab bioconjugate and imaged by stereomicroscopy to determine if tumor fluorescence predicted tumor response. Intact tumor fluorescence did not predict response. Tissue was harvested from untreated xenografts to evaluate ex vivo imaging. Cell lines were then evaluated in vitro for fluorescence imaging after Cy5.5-cetuximab bioconjugate labeling. The location of fluorescence observed in labeled cells was significantly different for cell lines that responded to treatment, relative to unresponsive cells. Tumors from cell lines that showed low internalized signal in vitro responded best to treatment with cetuximab. This preclinical model may aid in determining which cancer patients are best suited for cetuximab therapy. PMID:20505368

  7. Tumor growth and its effect on Magnetic Resonance Imaging signal

    NASA Astrophysics Data System (ADS)

    Cersosimo, Homero; Colon, Jorge; Ramos, Elio; Zypman, Fredy

    2000-03-01

    The goal of this project is twofold. On one hand, we have developed computer code based on simple probabilistic rules to model the growth (or shrinking) of cancerigenous tissue. We assume that initially there exists a differentiated cell, which has a time- dependent probability of reproducing. If it did reproduce, then we assume that it has a finite probability of dying before reproducing again. This simple model falls into the Eden-type kind, and presents appropriate bulk growth characteristics, as it follows Gompert observational law. We propose new methods of geometrical characterization of the tumor. Besides its total mass, we also consider higher multipolar order of mass distribution and surface fractal dimension. In addition, we study how the geometrical properties of the tumor affect the Magnetic Resonance Imaging (MRI) signal. To this end, we consider a human brain in the presence of radiofrequency fields. We calculate the MRI image of this object. Then, we introduce a tumor in the white-gray matter region and reobtain the MRI image. We associate the signal changes with the geometrical properties of the tumor.

  8. A deformable model for tracking tumors across consecutive imaging studies

    PubMed Central

    Nosher, John L.; Schneider, M. D. Benjamin; Foran, David J.

    2009-01-01

    Objective A deformable registration technique was developed and evaluated to track and quantify tumor response to radiofrequency ablation for patients with liver malignancies. Materials and methods The method uses the combined power of global and local alignment of pre- and post-treatment computed tomography image data sets. The strategy of the algorithm is to infer volumetric deformation based upon surface displacements using a linearly elastic finite element model (FEM). Using this framework, the major challenge for tracking tumor location is not the tissue mechanical properties for FEM modeling but rather the evaluation of boundary conditions. Three different methods were systematically investigated to automatically determine the boundary conditions defined by the correspondences on liver surfaces. Results Using both 2D synthetic phantoms and imaged 3D beef liver data we performed gold standard registration while measuring the accuracy of non-rigid deformation. The fact that the algorithms could support mean displacement error of tumor deformation up to 2 mm indicates that this technique may serve as a useful tool for surgical interventions. The method was further demonstrated and evaluated using consecutive imaging studies for three liver cancer patients. Conclusion The FEM-based surface registration technique provides accurate tracking and monitoring of tumor and surrounding tissue during the course of treatment and follow-up. PMID:19774096

  9. Clearance Pathways and Tumor Targeting of Imaging Nanoparticles

    PubMed Central

    Yu, Mengxiao; Zheng, Jie

    2016-01-01

    A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies. PMID:26149184

  10. Utility of tumor-avid photosensitizers in developing bifunctional agents for tumor imaging and/or phototherapy

    NASA Astrophysics Data System (ADS)

    Pandey, Suresh K.; Chen, Yihui; Zawada, Robert H.; Oseroff, Allan; Pandey, Ravindra K.

    2006-02-01

    HPPH (a chlorophyll-a analog) was linked with a cyanine dye and the resulting conjugate was found to be an efficient tumor imaging (fluorescence imaging) and photosensitizing agent (PDT). Our preliminary results suggest that tumor-avid porphyrin-based compounds can be used as vehicles for delivering the desired fluorophores to tumor for fluorescence imaging. In an early diagnosis of microscopic lesions in pre-clinical studies (C3H mice implanted with RIF tumors) the HPPH-cyanine dye conjugate showed tumor-imaging capability (λ ex: 780 nm, λ em: 860 nm) at the non- therapeutic doses that are 100 fold lower than those used therapeutically. Compared to the cyanine dye, the corresponding HPPH-conjugate showed enhanced long-term tumor imaging ability.

  11. Cyclic RGD peptide-labeled upconversion nanophosphors for tumor cell-targeted imaging.

    PubMed

    Zako, Tamotsu; Nagata, Hiroyasu; Terada, Naofumi; Utsumi, Arata; Sakono, Masafumi; Yohda, Masafumi; Ueda, Hiroshi; Soga, Kohei; Maeda, Mizuo

    2009-03-27

    One of the great challenges of oncology is to improve methods for early tumor detection. Thus tumor cell-targeted optical imaging has been intensively studied. Bioimaging with upconversion (UC) phosphors (UCPs) is of considerable interest due to a variety of possible applications taking advantage of infrared-to-visible luminescence. Here we report for the first time tumor cell-targeted UC imaging using UCPs modified with cyclic RGD peptide (RGD-Y2O3). Cyclic RGD peptide binds specifically to integrin alphavbeta3 which is highly expressed in a tumor cell surface of certain cancer types but not in normal tissues. Since UC emission from RGD-Y2O3 was observed for U87MG cancer cell (high integrin alphavbeta3 expression), but not for MCF-7 cancer cell (low integrin alphavbeta3 expression), this UC imaging is considered to be integrin alphavbeta3 specific. The non-invasive imaging of integrin alphavbeta3 expression using UCP-based probes will have great potential in cancer imaging in general in living subjects. PMID:19351594

  12. Magnetic Resonance Imaging and Other Imaging Modalities in Diagnostic and Tumor Response Evaluation.

    PubMed

    Lambregts, Doenja M J; Maas, Monique; Stokkel, Marcel P M; Beets-Tan, Regina G H

    2016-07-01

    Functional imaging is emerging as a valuable contributor to the clinical management of patients with rectal cancer. Techniques such as diffusion-weighted magnetic resonance imaging, perfusion imaging, and positron emission tomography can offer meaningful insights into tissue architecture, vascularity, and metabolism. Moreover, new techniques targeting other aspects of tumor biology are now being developed and studied. This study reviews the potential role of functional imaging for the diagnosis, treatment monitoring, and assessment of prognosis in patients with rectal cancer. PMID:27238470

  13. TH-E-17A-10: Markerless Lung Tumor Tracking Based On Beams Eye View EPID Images

    SciTech Connect

    Chiu, T; Kearney, V; Liu, H; Jiang, L; Foster, R; Mao, W; Rozario, T; Bereg, S; Klash, S

    2014-06-15

    Purpose: Dynamic tumor tracking or motion compensation techniques have proposed to modify beam delivery following lung tumor motion on the flight. Conventional treatment plan QA could be performed in advance since every delivery may be different. Markerless lung tumor tracking using beams eye view EPID images provides a best treatment evaluation mechanism. The purpose of this study is to improve the accuracy of the online markerless lung tumor motion tracking method. Methods: The lung tumor could be located on every frame of MV images during radiation therapy treatment by comparing with corresponding digitally reconstructed radiograph (DRR). A kV-MV CT corresponding curve is applied on planning kV CT to generate MV CT images for patients in order to enhance the similarity between DRRs and MV treatment images. This kV-MV CT corresponding curve was obtained by scanning a same CT electron density phantom by a kV CT scanner and MV scanner (Tomotherapy) or MV CBCT. Two sets of MV DRRs were then generated for tumor and anatomy without tumor as the references to tracking the tumor on beams eye view EPID images. Results: Phantom studies were performed on a Varian TrueBeam linac. MV treatment images were acquired continuously during each treatment beam delivery at 12 gantry angles by iTools. Markerless tumor tracking was applied with DRRs generated from simulated MVCT. Tumors were tracked on every frame of images and compared with expected positions based on programed phantom motion. It was found that the average tracking error were 2.3 mm. Conclusion: This algorithm is capable of detecting lung tumors at complicated environment without implanting markers. It should be noted that the CT data has a slice thickness of 3 mm. This shows the statistical accuracy is better than the spatial accuracy. This project has been supported by a Varian Research Grant.

  14. Monte Carlo design of optimal wire mesh collimator for breast tumor imaging process

    NASA Astrophysics Data System (ADS)

    Saad, W. H. M.; Roslan, R. E.; Mahdi, M. A.; Choong, W.-S.; Saion, E.; Saripan, M. I.

    2011-08-01

    This paper presents the modeling of breast tumor imaging process using wire mesh collimator gamma camera. Previous studies showed that the wire mesh collimator has a potential to improve the sensitivity of the tumor detection. In this paper, we extend our research significantly, to find an optimal configuration of the wire mesh collimator specifically for semi-compressed breast tumor detection, by looking into four major factors: weight, sensitivity, spatial resolution and tumor contrast. The numbers of layers in the wire mesh collimator is varied to optimize the collimator design. The statistical variations of the results are studied by simulating multiple realizations for each experiment using different starting random numbers. All the simulation environments are modeled using Monte Carlo N-Particle Code (MCNP). The quality of the detection is measured directly by comparing the sensitivity, spatial resolution and tumor contrast of the images produced by the wire mesh collimator and benchmarked that with a standard multihole collimator. The proposed optimal configuration of the wire mesh collimator is optimized by selecting the number of layers in wire mesh collimator, where the tumor contrast shows a relatively comparable value to the multihole collimator, when it is tested with uniformly semi-compressed breast phantom. The wire mesh collimator showed higher number of sensitivity because of its loose arrangement while the spatial resolution of wire mesh collimator does not shows much different compared to the multihole collimator. With a relatively good tumor contrast and spatial resolution, and increased in sensitivity, a new proposed wire mesh collimator gives a significant improvement in the wire mesh collimator design for breast cancer imaging process. The proposed collimator configuration is reduced to 44.09% from the total multihole collimator weight.

  15. Image fusion for visualization of hepatic vasculature and tumors

    NASA Astrophysics Data System (ADS)

    Chou, Jin-Shin; Chen, Shiuh-Yung J.; Sudakoff, Gary S.; Hoffmann, Kenneth R.; Chen, Chin-Tu; Dachman, Abraham H.

    1995-05-01

    We have developed segmentation and simultaneous display techniques to facilitate the visualization of the three-dimensional spatial relationships between organ structures and organ vasculature. We concentrate on the visualization of the liver based on spiral computed tomography images. Surface-based 3-D rendering and maximal intensity projection algorithms are used for data visualization. To extract the liver in the serial of images accurately and efficiently, we have developed a user-friendly interactive program with a deformable-model segmentation. Surface rendering techniques are used to visualize the extracted structures, adjacent contours are aligned and fitted with a Bezier surface to yield a smooth surface. Visualization of the vascular structures, portal and hepatic veins, is achieved by applying a MIP technique to the extracted liver volume. To integrate the extracted structures they are surface-rendered and their MIP images are aligned and a color table is designed for simultaneous display of the combined liver/tumor and vasculature images. By combining the 3-D surface rendering and MIP techniques, portal veins, hepatic veins, and hepatic tumor can be inspected simultaneously and their spatial relationships can be more easily perceived. The proposed technique will be useful for visualization of both hepatic neoplasm and vasculature in surgical planning for tumor resection or living-donor liver transplantation.

  16. Magnetic Resonance Imaging Protocol Optimization for Delineation of Gross Tumor Volume in Hypopharyngeal and Laryngeal Tumors

    SciTech Connect

    Verduijn, Gerda M.; Bartels, Lambertus W. Ph.D.; Pameijer, Frank A.

    2009-06-01

    Purpose: To optimize the use of MRI for delineation of gross tumor volume for radiotherapy treatment planning purposes in hypopharyngeal and laryngeal tumors. Methods and Materials: Magnetic resonance images (T1 weighted and T2 weighted) of a healthy volunteer were acquired using a 1.5 T and 3.0 T MR scanner. Various receiver coils were investigated that were compatible with the immobilization mask needed for reliable coregistration with computed tomography data. For the optimal receiver coil, the influence of resolution, slice thickness, and strength of magnetic field on the signal-to-noise ratio (SNR) was studied. Feasibility of the definitive protocol was tested on patients with hypopharyngeal (n = 19) and laryngeal (n = 42) carcinoma. Results: Large differences in SNR were obtained for the various coils. The SNR values obtained using surface coils that were compatible with the immobilization mask were three times higher than those obtained using a standard head-and-neck coil and five times higher than those obtained using a body coil. High-resolution images (0.4 x 0.4 x 4 mm{sup 3}) showed superior anatomic detail and resulted in a 4-min scan time. Image quality at 3.0 T was not significantly better compared with 1.5 T. In 3 patients the MR study could not be performed; for 5 patients images were severely deteriorated by motion artefacts. High-quality MR images were obtained in 53 patients. Conclusions: High-resolution MR images of the hypopharynx and larynx can be obtained in the majority of patients using surface receiver coils in combination with the radiotherapy mask. These MR images can be successfully used for tumor delineation in radiotherapy.

  17. Development of photostabilized asymmetrical cyanine dyes for in vivo photoacoustic imaging of tumors

    NASA Astrophysics Data System (ADS)

    Onoe, Satoru; Temma, Takashi; Kanazaki, Kengo; Ono, Masahiro; Saji, Hideo

    2015-09-01

    Photoacoustic imaging (PAI) contributes to tumor diagnosis through the use of PAI probes that effectively accumulate in tumors. Previously, we developed a symmetrical cyanine dye, IC7-1-Bu, which showed high potential as a PAI probe because of its high tumor targeting ability and sufficient in vivo PA signal. However, IC7-1-Bu lacks photostability for multiple laser irradiations, so we developed stabilized PAI probes using IC7-1-Bu as a lead compound. We focused on the effect of singlet oxygen (O) generated by excited PAI probes on probe degeneration. We introduced a triplet-state quencher (TSQ) moiety into IC7-1-Bu to quench O generation and designed three IC-n-T derivatives with different linker lengths (n indicates linker length). The IC-n-T derivatives emitted in vitro PA signals that were comparable to IC7-1-Bu and significantly reduced O generation while showing improved photostability against multiple irradiations. Of the three derivatives evaluated, IC-5-T accumulated in tumors effectively to allow clear PAI of tumors in vivo. Furthermore, the photostability of IC-5-T was 1.5-fold higher than that of IC7-1-Bu in in vivo sequential PAI. These results suggest that IC-5-T is a potential PAI probe for in vivo sequential tumor imaging.

  18. Development of photostabilized asymmetrical cyanine dyes for in vivo photoacoustic imaging of tumors.

    PubMed

    Onoe, Satoru; Temma, Takashi; Kanazaki, Kengo; Ono, Masahiro; Saji, Hideo

    2015-09-01

    Photoacoustic imaging (PAI) contributes to tumor diagnosis through the use of PAI probes that effectively accumulate in tumors. Previously, we developed a symmetrical cyanine dye, IC7-1-Bu, which showed high potential as a PAI probe because of its high tumor targeting ability and sufficient in vivo PA signal. However, IC7-1-Bu lacks photostability for multiple laser irradiations, so we developed stabilized PAI probes using IC7-1-Bu as a lead compound. We focused on the effect of singlet oxygen (1O2) generated by excited PAI probes on probe degeneration. We introduced a triplet-state quencher (TSQ) moiety into IC7-1-Bu to quench 1O2 generation and designed three IC-n-T derivatives with different linker lengths (n indicates linker length). The IC-n-T derivatives emitted in vitro PA signals that were comparable to IC7-1-Bu and significantly reduced 1O2 generation while showing improved photostability against multiple irradiations. Of the three derivatives evaluated, IC-5-T accumulated in tumors effectively to allow clear PAI of tumors in vivo. Furthermore, the photostability of IC-5-T was 1.5-fold higher than that of IC7-1-Bu in in vivo sequential PAI. These results suggest that IC-5-T is a potential PAI probe for in vivo sequential tumor imaging. PMID:26358819

  19. Imaging angiogenesis, inflammation, and metastasis in the tumor microenvironment with magnetic resonance imaging.

    PubMed

    Serres, Sébastien; O'Brien, Emma R; Sibson, Nicola R

    2014-01-01

    With the development of new imaging techniques, the potential for probing the molecular, cellular, and structural components of the tumor microenvironment in situ has increased dramatically. A multitude of imaging modalities have been successfully employed to probe different aspects of the tumor microenvironment, including expression of molecules, cell motion, cellularity, vessel permeability, vascular perfusion, metabolic and physiological changes, apoptosis, and inflammation. This chapter focuses on the most recent advances in magnetic resonance imaging methods, which offer a number of advantages over other methodologies, including high spatial resolution and the use of nonionizing radiation, as well as the use of such methods in the context of primary and secondary brain tumors. It also highlights how they can be used to assess the molecular and cellular changes in the tumor microenvironment in response to therapy. PMID:24272363

  20. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion.

    PubMed

    Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio

    2015-11-01

    Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation. PMID:26276694

  1. New Glucocyclic RGD Dimers for Positron Emission Tomography Imaging of Tumor Integrin Receptors.

    PubMed

    Lee, Ji Woong; Park, Ji-Ae; Lee, Yong Jin; Shin, Un Chol; Kim, Suhng Wook; Kim, Byung Il; Lim, Sang Moo; An, Gwang Il; Kim, Jung Young; Lee, Kyo Chul

    2016-08-01

    Most studies of radiolabeled arginine-glycine-aspartic acid (RGD) peptides have shown in vitro affinity for integrin ανβ3, allowing for the targeting of receptor-positive tumors in vivo. However, major differences have been found in the pharmacokinetic profiles of different radiolabeled RGD peptide analogs. The purposes of this study were to prepare (64)Cu-DOTA-gluco-E[c(RGDfK)]2 (R8), (64)Cu-NOTA-gluco-E[c(RGDfK)]2 (R9), and (64)Cu-NODAGA-gluco-E[c(RGDfK)]2 (R10) and compare their pharmacokinetics and tumor imaging properties using small-animal positron emission tomography (PET). All three compounds were produced with high specific activity within 10 minutes. The IC50 values were similar for all the substances, and their affinities were greater than that of c(RGDyK). R8, R9, and R10 were stable for 24 hours in human and mouse serums and showed high uptake in U87MG tumors with high tumor-to-blood ratios. Compared to the control, a cyclic RGD peptide dimer without glucosamine, R10, showed low uptake in the liver. Because of their good imaging qualities and improved pharmacokinetics, (64)Cu-labeled dimer RGD conjugates (R8, R9, and R10) may have potential applications as PET radiotracers. R9 (NOTA) with highly in vivo stability consequentially showed an improved PET tumor uptake than R8 (DOTA) or R10 (NODAGA). PMID:27403677

  2. A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors

    PubMed Central

    Gabrielson, Matthew; Lisok, Ala; Wharram, Bryan; Sysa-Shah, Polina; Azad, Babak Behnam; Pomper, Martin G.; Nimmagadda, Sridhar

    2016-01-01

    Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIR-PD-L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings. PMID:26848870

  3. Improved real-time imaging spectrometer

    NASA Technical Reports Server (NTRS)

    Lambert, James L. (Inventor); Chao, Tien-Hsin (Inventor); Yu, Jeffrey W. (Inventor); Cheng, Li-Jen (Inventor)

    1993-01-01

    An improved AOTF-based imaging spectrometer that offers several advantages over prior art AOTF imaging spectrometers is presented. The ability to electronically set the bandpass wavelength provides observational flexibility. Various improvements in optical architecture provide simplified magnification variability, improved image resolution and light throughput efficiency and reduced sensitivity to ambient light. Two embodiments of the invention are: (1) operation in the visible/near-infrared domain of wavelength range 0.48 to 0.76 microns; and (2) infrared configuration which operates in the wavelength range of 1.2 to 2.5 microns.

  4. Improving PET imaging for breast cancer using virtual pinhole PET half-ring insert

    NASA Astrophysics Data System (ADS)

    Mathews, Aswin John; Komarov, Sergey; Wu, Heyu; O'Sullivan, Joseph A.; Tai, Yuan-Chuan

    2013-09-01

    A PET insert with detector having smaller crystals and placed near a region of interest in a conventional PET scanner can improve image resolution locally due to the virtual-pinhole PET (VP-PET) effect. This improvement is from the higher spatial sampling of the imaging area near the detector. We have built a prototype half-ring PET insert for head-and-neck cancer imaging applications. In this paper, we extend the use of the insert to breast imaging and show that such a system provides high resolution images of breast and axillary lymph nodes while maintaining the full imaging field of view capability of a clinical PET scanner. We characterize the resolution and contrast recovery for tumors across the imaging field of view. First, we model the system using Monte Carlo methods to determine its theoretical limit of improvement. Simulations were conducted with hot spherical tumors embedded in background activity at tumor-to-background contrast ranging from 3:1 to 12:1. Tumors are arranged in a Derenzo-like pattern with their diameters ranging from 2 to 12 mm. Experimental studies were performed using a chest phantom with cylindrical breast attachment. Tumors of different sizes arranged in a Derenzo-like pattern with tumor-to-background ratio of 6:1 are inserted into the breast phantom. Imaging capability of mediastinum and axillary lymph nodes is explored. Both Monte Carlo simulations and experiment show clear improvement in image resolution and contrast recovery with VP-PET half-ring insert. The degree of improvement in resolution and contrast recovery depends on location of the tumor. The full field of view imaging capability is shown to be maintained. Minor artifacts are introduced in certain regions.

  5. Improved Interactive Medical-Imaging System

    NASA Technical Reports Server (NTRS)

    Ross, Muriel D.; Twombly, Ian A.; Senger, Steven

    2003-01-01

    An improved computational-simulation system for interactive medical imaging has been invented. The system displays high-resolution, three-dimensional-appearing images of anatomical objects based on data acquired by such techniques as computed tomography (CT) and magnetic-resonance imaging (MRI). The system enables users to manipulate the data to obtain a variety of views for example, to display cross sections in specified planes or to rotate images about specified axes. Relative to prior such systems, this system offers enhanced capabilities for synthesizing images of surgical cuts and for collaboration by users at multiple, remote computing sites.

  6. Imaging of primary bone tumors in veterinary medicine: which differences?

    PubMed

    Vanel, Maïa; Blond, Laurent; Vanel, Daniel

    2013-12-01

    Veterinary medicine is most often a mysterious world for the human doctors. However, animals are important for human medicine thanks to the numerous biological similarities. Primary bone tumors are not uncommon in veterinary medicine and especially in small domestic animals as dogs and cats. As in human medicine, osteosarcoma is the most common one and especially in the long bones extremities. In the malignant bone tumor family, chondrosarcoma, fibrosarcoma and hemangiosarcoma are following. Benign bone tumors as osteoma, osteochondroma and bone cysts do exist but are rare and of little clinical significance. Diagnostic modalities used depend widely on the owner willing to treat his animal. Radiographs and bone biopsy are the standard to make a diagnosis but CT, nuclear medicine and MRI are more an more used. As amputation is treatment number one in appendicular bone tumor in veterinary medicine, this explains on the one hand why more recent imaging modalities are not always necessary and on the other hand, that prognostic on large animals is so poor that it is not much studied. Chemotherapy is sometimes associated with the surgery procedure, depending on the aggressivity of the tumor. Although, the strakes differs a lot between veterinary and human medicine, biological behavior are almost the same and should led to a beneficial team work between all. PMID:22197093

  7. Advanced Imaging for Biopsy Guidance in Primary Brain Tumors

    PubMed Central

    Tsiouris, Apostolos J; Ramakrishna, Rohan

    2016-01-01

    Accurate glioma sampling is required for diagnosis and establishing eligibility for relevant clinical trials. MR-based perfusion and spectroscopy sequences supplement conventional MR in noninvasively predicting the areas of highest tumor grade for biopsy. We report the case of a patient with gliomatosis cerebri and multifocal patchy enhancement in whom the combination of advanced and conventional imaging attributes successfully guided a diagnostic biopsy. PMID:27014538

  8. Finite element model-based tumor registration of microPET and high-resolution MR images for photodynamic therapy in mice

    NASA Astrophysics Data System (ADS)

    Fei, Baowei; Wang, Hesheng; Muzic, Raymond F., Jr.; Flask, Chris A.; Feyes, Denise; Wilson, David L.; Duerk, Jeffrey L.; Oleinick, Nancy L.

    2006-03-01

    We are investigating imaging techniques to study the tumor response to photodynamic therapy (PDT). PET can provide physiological and functional information. High-resolution MRI can provide anatomical and morphological changes. Image registration can combine MRI and PET images for improved tumor monitoring. In this study, we acquired high-resolution MRI and microPET [ 18F]fluorodeoxyglucose (FDG) images from C3H mice with RIF-1 tumors that were treated with Pc 4-based PDT. For tumor registration, we developed a finite element model (FEM)-based deformable registration scheme. To assess the registration quality, we performed slice by slice review of both image volumes, computed the volume overlap ratios, and visualized both volumes in color overlay. The mean volume overlap ratios for tumors were 94.7% after registration. Registration of high-resolution MRI and microPET images combines anatomical and functional information of the tumors and provides a useful tool for evaluating photodynamic therapy.

  9. Characteristic power Doppler sonographic images of tumorous and non-tumorous buccal space lesions

    PubMed Central

    Ogura, I; Kaneda, T; Sasaki, Y; Sekiya, K; Tokunaga, S

    2013-01-01

    Objectives: The aim of this study was to evaluate the characteristic power Doppler sonographic images of buccal space tumorous and non-tumorous lesions. Methods: 48 patients with buccal space lesions were evaluated with greyscale sonography followed by power Doppler sonography with a 12 MHz linear transducer. On greyscale sonography, buccal space lesions were assessed for the boundary (clear or unclear), echogenicity (hypoechoic or isoechoic) and internal architecture (homogeneous or heterogeneous). Power Doppler sonography was performed to evaluate the vascular signals within the buccal space lesions. Results: 48 lesions were found in the 48 patients; of these 48 lesions, 28 were tumourous and 20 were non-tumourous. In the 28 tumours, 15 cases showed clear boundaries, 15 cases were hypoechoic relative to adjacent tissues and 22 cases presented with a heterogeneous appearance on greyscale sonography. The internal vascularity of 19 tumours was shown using power Doppler sonography. In the 20 non-tumorous lesions, 11 cases showed clear boundaries, 17 cases were hypoechoic relative to adjacent tissues and 13 cases presented with a homogeneous appearance on greyscale sonography. 18 non-tumorous lesions showed no internal vascularity using power Doppler sonography. Logistic multivariate regression analysis between the tumour group and the non-tumorous lesions group demonstrated that the internal architecture (odds ratio = 8.270, p = 0.029) and vascular signals (odds ratio = 17.533, p = 0.003) were significant variables. Conclusions: Power Doppler sonography is a useful technique for the differential diagnosis of tumorous and non-tumorous buccal space lesions. PMID:23520393

  10. Pancreas tumor model in rabbit imaged by perfusion CT scans

    NASA Astrophysics Data System (ADS)

    Gunn, Jason; Tichauer, Kenneth; Moodie, Karen; Kane, Susan; Hoopes, Jack; Stewart, Errol E.; Hadway, Jennifer; Lee, Ting-Yim; Pereira, Stephen P.; Pogue, Brian W.

    2013-03-01

    The goal of this work was to develop and validate a pancreas tumor animal model to investigate the relationship between photodynamic therapy (PDT) effectiveness and photosensitizer drug delivery. More specifically, this work lays the foundation for investigating the utility of dynamic contrast enhanced blood perfusion imaging to be used to inform subsequent PDT. A VX2 carcinoma rabbit cell line was grown in the tail of the pancreas of three New Zealand White rabbits and approximately 3-4 weeks after implantation the rabbits were imaged on a CT scanner using a contrast enhanced perfusion protocol, providing parametric maps of blood flow, blood volume, mean transit time, and vascular permeability surface area product.

  11. Advanced endoscopic imaging to improve adenoma detection

    PubMed Central

    Neumann, Helmut; Nägel, Andreas; Buda, Andrea

    2015-01-01

    Advanced endoscopic imaging is revolutionizing our way on how to diagnose and treat colorectal lesions. Within recent years a variety of modern endoscopic imaging techniques was introduced to improve adenoma detection rates. Those include high-definition imaging, dye-less chromoendoscopy techniques and novel, highly flexible endoscopes, some of them equipped with balloons or multiple lenses in order to improve adenoma detection rates. In this review we will focus on the newest developments in the field of colonoscopic imaging to improve adenoma detection rates. Described techniques include high-definition imaging, optical chromoendoscopy techniques, virtual chromoendoscopy techniques, the Third Eye Retroscope and other retroviewing devices, the G-EYE endoscope and the Full Spectrum Endoscopy-system. PMID:25789092

  12. A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy

    PubMed Central

    Liu, Yang; Ashton, Jeffrey R.; Moding, Everett J.; Yuan, Hsiangkuo; Register, Janna K.; Fales, Andrew M.; Choi, Jaeyeon; Whitley, Melodi J.; Zhao, Xiaoguang; Qi, Yi; Ma, Yan; Vaidyanathan, Ganesan; Zalutsky, Michael R.; Kirsch, David G.; Badea, Cristian T.; Vo-Dinh, Tuan

    2015-01-01

    Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy. PMID:26155311

  13. Molecular Magnetic Resonance Imaging of Tumor Response to Therapy

    PubMed Central

    Shuhendler, Adam J.; Ye, Deju; Brewer, Kimberly D.; Bazalova-Carter, Magdalena; Lee, Kyung-Hyun; Kempen, Paul; Dane Wittrup, K.; Graves, Edward E.; Rutt, Brian; Rao, Jianghong

    2015-01-01

    Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring. PMID:26440059

  14. Infrared microspectroscopic imaging of benign breast tumor tissue sections

    NASA Astrophysics Data System (ADS)

    Fabian, H.; Lasch, P.; Boese, M.; Haensch, W.

    2003-12-01

    We have applied infrared microspectroscopic imaging for the examination of benign breast tumor tissue sections. The IR spectra of the sections were obtained by classical point microscopy with a movable stage and via a microscope equipped with a focal plane array detector. The infrared microscopic data were analysed using functional group mapping techniques and cluster analysis. The output values of the two procedures were reassembled into infrared images of the tissues, and were compared with standard staining images of the corresponding tissue region. The comparative examination of identical tissue sections by the two IR approaches enabled us to assess potential problems associated with tissue microheterogeneity. It was found that in case of fibroadenoma, a benign lesion located in breast ducts, point microscopy with a spot size of ˜30 μm is a useful practical approach which minimizes the possibility of 'contamination' of the spectra because of spectral averaging of all tissue components present in the corresponding microareas. A comparison of the spectra of the benign breast tumor with those of a malignant ductal carcinoma in situ revealed that IR microspectroscopy has the potential to differentiate between these two breast tumor types.

  15. Diffusion tensor imaging using a high-temperature superconducting resonator in a 3 T magnetic resonance imaging for a spontaneous rat brain tumor

    NASA Astrophysics Data System (ADS)

    Lin, In-Tsang; Yang, Hong-Chang; Chen, Jyh-Horng

    2013-02-01

    This study investigates the peri-tumor signal abnormalities of a spontaneous brain tumor in a rat by using a 4 cm high-temperature superconducting (HTS) surface resonator. Fractional anisotropy (FA) values derived from diffusion tensor imaging reflect the interstitial characteristic of the peri-lesional tissues of brain tumors. Low FA indicates interstitial tumor infiltration and tissue injury, while high FA indicates better tissue integrity. Better delineation of tissue contents obtained by the HTS surface resonator at 77 K may facilitate therapeutic strategy and improve clinical outcomes.

  16. Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

    PubMed Central

    Glasgow, Micah D. K.; Chougule, Mahavir B.

    2016-01-01

    Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID:26554150

  17. Magnetic Resonance Imaging Features of a Juxtaglomerular Cell Tumor

    PubMed Central

    Kang, Suhai; Guo, Aitao; Wang, Haiyi; Ma, Lu; Xie, Zongyu; Li, Jinglong; Tonge, Xinyuan; Ye, Huiyi

    2015-01-01

    Objective: To retrospectively determine whether magnetic resonance imaging (MRI) findings can help differentiate a juxtaglomerular cell tumor (JCT) from clear cell renal cell carcinoma (ccRCC). Materials and Methods: Eight patients with JCTs and 24 patients with pathologically proven ccRCC were included for image analysis. All patients underwent unenhanced MRI and dynamic contrast-enhanced MRI. Fat-suppressed T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), in- and opposed-phase imaging, and fat-suppressed preliver acquisitions with volume acceleration sequences were performed before enhancement. After the administration of contrast, dynamic imaging was performed in the corticomedullary, nephrographic, and excretory phases. Student's t-test, t′-test, Chi-square test, and nonparametric Kruskal–Wallis H-test were used to determine the significance of the difference between the two groups. The sensitivity and specificity of the MRI findings were calculated. Results: In patients with a JCT, a cystic part of the lesion of <10%, isointensity or mild hyperintensity on T2WI, heterogeneous hyperintensity on DWI, less signal drop (<10%) in in- and opposed-phase imaging, and a degree of enhancement <200% in the corticomedullary phase showed statistically significant differences compared with those of ccRCC (P < 0.05). After combining a lower apparent diffusion coefficient (ADC) value (heterogeneous hyperintensity) on DWI and a degree of enhancement <200% in the corticomedullary phase using a parallel test, the sensitivity and specificity were 90.9% and 91.7%, respectively. Conclusions: Isointensity or mild hyperintensity on T2WI, a lower ADC value (heterogeneous hyperintensity) on DWI, and a degree of enhancement <200% in the corticomedullary phase are the major MRI findings for JCTs, combined with relative clinical manifestations and excluding other renal masses. A main solid tumor, less signal drop (<10%) in in- and opposed-phase imaging, and a less

  18. F-18 fluoromisonidazole for imaging tumor hypoxia: imaging the microenvironment for personalized cancer therapy.

    PubMed

    Rajendran, Joseph G; Krohn, Kenneth A

    2015-03-01

    Hypoxia in solid tumors is one of the seminal mechanisms for developing aggressive trait and treatment resistance in solid tumors. This evolutionarily conserved biological mechanism along with derepression of cellular functions in cancer, although resulting in many challenges, provide us with opportunities to use these adversities to our advantage. Our ability to use molecular imaging to characterize therapeutic targets such as hypoxia and apply this information for therapeutic interventions is growing rapidly. Evaluation of hypoxia and its biological ramifications to effectively plan appropriate therapy that can overcome the cure-limiting effects of hypoxia provides an objective means for treatment selection and planning. Fluoromisonidazole (FMISO) continues to be the lead radiopharmaceutical in PET imaging for the evaluation, prognostication, and quantification of tumor hypoxia, one of the key elements of the tumor microenvironment. FMISO is less confounded by blood flow, and although the images have less contrast than FDG-PET, its uptake after 2 hours is an accurate reflection of inadequate regional oxygen partial pressure at the time of radiopharmaceutical administration. By virtue of extensive clinical utilization, FMISO remains the lead candidate for imaging and quantifying hypoxia. The past decade has seen significant technological advances in investigating hypoxia imaging in radiation treatment planning and in providing us with the ability to individualize radiation delivery and target volume coverage. The presence of widespread hypoxia in the tumor can be effectively targeted with a systemic hypoxic cell cytotoxin or other agents that are more effective with diminished oxygen partial pressure, either alone or in combination. Molecular imaging in general and hypoxia imaging in particular will likely become an important in vivo imaging biomarker of the future, complementing the traditional direct tissue sampling methods by providing a snap shot of a primary

  19. F18 Fluoromisonidazole for Imaging Tumor Hypoxia: Imaging the Microenvironment for Personalized Cancer Therapy

    PubMed Central

    Rajendran, JG; Krohn, KA

    2014-01-01

    Hypoxia in solid tumors is one of the seminal mechanisms for developing aggressive trait and treatment resistsance in solid tumors. This evolutionarily conserved biological mechanism along with de-repression of cellular functions in cancer, although resulting in many challenges, provide us with opportunities to use these adversities to our advantage. Our ability to use molecular imaging to characterize therapeutic targets such as hypoxia and apply this information for therapeutic interventions is growing rapidly. Evaluation of hypoxia and its biological ramifications to effectively plan appropriate therapy that can overcome the cure-limiting effects of hypoxia provides an objective means for treatment selection and planning. FMISO PET imaging of tumor hypoxia continues to be the lead radiopharmaceutical for the evaluation, prognostication and quantification of hypoxia, one of the key elements of the tumor microenvironment. FMISO is less confounded by blood flow and, although the images have less contrast than FDG PET, its uptake after 2 hours is an accurate reflection of inadequate regional Po2 at the time of radiopharmaceutical administration. By virtue of extensive clinical utilization, FMISO remains the lead candidate for imaging and quantifying hypoxia. The past decade has seen significant technological advances in investigating hypoxia imaging in radiation treatment planning and in providing us with the ability to individualize radiation delivery and target volume coverage. The presence of widespread hypoxia in the tumor can be effectively targeted with a systemic hypoxic cell cytotoxin or other agents that are more effective with diminished PO2, either alone or in combination. Molecular imaging in general and hypoxia imaging in particular will likely become an important in vivo imaging biomarker of the future, complementing the traditional direct tissue sampling methods by providing a snap shot of a primary tumor and metastatic disease and in following

  20. Can coffee improve image guidance?

    NASA Astrophysics Data System (ADS)

    Wirz, Raul; Lathrop, Ray A.; Godage, Isuru S.; Burgner-Kahrs, Jessica; Russell, Paul T.; Webster, Robert J.

    2015-03-01

    Anecdotally, surgeons sometimes observe large errors when using image guidance in endonasal surgery. We hypothesize that one contributing factor is the possibility that operating room personnel might accidentally bump the optically tracked rigid body attached to the patient after registration has been performed. In this paper we explore the registration error at the skull base that can be induced by simulated bumping of the rigid body, and find that large errors can occur when simulated bumps are applied to the rigid body. To address this, we propose a new fixation method for the rigid body based on granular jamming (i.e. using particles like ground coffee). Our results show that our granular jamming fixation prototype reduces registration error by 28%-68% (depending on bump direction) in comparison to a standard Brainlab reference headband.

  1. Normalized fluorescence lifetime imaging for tumor identification and margin delineation

    NASA Astrophysics Data System (ADS)

    Sherman, Adria J.; Papour, Asael; Bhargava, Siddharth; Taylor, Zach; Grundfest, Warren S.; Stafsudd, Oscar M.

    2013-03-01

    Fluorescence lifetime imaging microscopy (FLIM) is a technique that has been proven to produce quantitative and qualitative differentiation and identification of substances with good specificity and sensitivity based on lifetime extracted information. This technique has shown the ability to also differentiate between a wide range of tissue types to identify malignant from benign tissue in vivo and ex vivo. However, the complexity, long duration and effort required to generate this information has limited the adoption of these techniques in a clinical setting. Our group has developed a time-resolved imaging system (patent pending) that does not require the extraction of lifetimes or use of complex curve fitting algorithms to display the needed information. The technique, entitled Lifetime Fluorescence Imaging (LFI, or NoFYI), converts fluorescence lifetime decay information directly into visual contrast. Initial studies using Fluorescein and Rhodamine-B demonstrated the feasibility of this approach. Subsequent studies demonstrated the ability to separate collagen and elastin powders. The technique uses nanosecond pulsed UV LEDs at 375 nm for average illumination intensities of ~4.5 μW on the tissue surface with detection by a gated CCD camera. To date, we have imaged 11 surgical head and neck squamous cell carcinoma and brain cancer biopsy specimens including 5 normal and 6 malignant samples. Images at multiple wavelengths clearly demonstrate differentiation between benign and malignant tissue, which was later confirmed by histology. Contrast was obtained between fluorophores with 35 μm spatial resolution and an SNR of ~30 dB allowing us to clearly define tumor margins in these highly invasive cancers. This method is capable of providing both anatomical and chemical information for the pathologist and the surgeon. These results suggest that this technology has a possible role in identifying tumors in tissue specimens and detecting tumor margins

  2. Quantification of Heterogeneity as a Biomarker in Tumor Imaging: A Systematic Review

    PubMed Central

    Alic, Lejla; Niessen, Wiro J.; Veenland, Jifke F.

    2014-01-01

    Background Many techniques are proposed for the quantification of tumor heterogeneity as an imaging biomarker for differentiation between tumor types, tumor grading, response monitoring and outcome prediction. However, in clinical practice these methods are barely used. This study evaluates the reported performance of the described methods and identifies barriers to their implementation in clinical practice. Methodology The Ovid, Embase, and Cochrane Central databases were searched up to 20 September 2013. Heterogeneity analysis methods were classified into four categories, i.e., non-spatial methods (NSM), spatial grey level methods (SGLM), fractal analysis (FA) methods, and filters and transforms (F&T). The performance of the different methods was compared. Principal Findings Of the 7351 potentially relevant publications, 209 were included. Of these studies, 58% reported the use of NSM, 49% SGLM, 10% FA, and 28% F&T. Differentiation between tumor types, tumor grading and/or outcome prediction was the goal in 87% of the studies. Overall, the reported area under the curve (AUC) ranged from 0.5 to 1 (median 0.87). No relation was found between the performance and the quantification methods used, or between the performance and the imaging modality. A negative correlation was found between the tumor-feature ratio and the AUC, which is presumably caused by overfitting in small datasets. Cross-validation was reported in 63% of the classification studies. Retrospective analyses were conducted in 57% of the studies without a clear description. Conclusions In a research setting, heterogeneity quantification methods can differentiate between tumor types, grade tumors, and predict outcome and monitor treatment effects. To translate these methods to clinical practice, more prospective studies are required that use external datasets for validation: these datasets should be made available to the community to facilitate the development of new and improved methods. PMID:25330171

  3. Preclinical evaluation of a novel cyanine dye for tumor imaging with in vivo photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Temma, Takashi; Onoe, Satoru; Kanazaki, Kengo; Ono, Masahiro; Saji, Hideo

    2014-09-01

    Photoacoustic imaging (PA imaging or PAI) has shown great promise in the detection and monitoring of cancer. Although nanocarrier-based contrast agents have been studied for use in PAI, small molecule contrast agents are required due to their ease of preparation, cost-effectiveness, and low toxicity. Here, we evaluated the usefulness of a novel cyanine dye IC7-1-Bu as a PAI contrast agent without conjugated targeting moieties for in vivo tumor imaging in a mice model. Basic PA characteristics of IC7-1-Bu were compared with indocyanine green (ICG), a Food and Drug Administration approved dye, in an aqueous solution. We evaluated the tumor accumulation profile of IC7-1-Bu and ICG by in vivo fluorescence imaging. In vivo PAI was then performed with a photoacoustic tomography system 24 and 48 h after intravenous injection of IC7-1-Bu into tumor bearing mice. IC7-1-Bu showed about a 2.3-fold higher PA signal in aqueous solution compared with that of ICG. Unlike ICG, IC7-1-Bu showed high tumor fluorescence after intravenous injection. In vivo PAI provided a tumor to background PA signal ratio of approximately 2.5 after intravenous injection of IC7-1-Bu. These results indicate that IC7-1-Bu is a promising PAI contrast agent for cancer imaging without conjugation of targeting moieties.

  4. Mutual-information-corrected tumor displacement using intraoperative ultrasound for brain shift compensation in image-guided neurosurgery

    NASA Astrophysics Data System (ADS)

    Ji, Songbai; Hartov, Alex; Roberts, David; Paulsen, Keith

    2008-03-01

    Intraoperative ultrasound (iUS) has emerged as a practical neuronavigational tool for brain shift compensation in image-guided tumor resection surgeries. The use of iUS is optimized when coregistered with preoperative magnetic resonance images (pMR) of the patient's head. However, the fiducial-based registration alone does not necessarily optimize the alignment of internal anatomical structures deep in the brain (e.g., tumor) between iUS and pMR. In this paper, we investigated and evaluated an image-based re-registration scheme to maximize the normalized mutual information (nMI) between iUS and pMR to improve tumor boundary alignment using the fiducial registration as a starting point for optimization. We show that this scheme significantly (p<<0.001) reduces tumor boundary misalignment pre-durotomy. The same technique was employed to measure tumor displacement post-durotomy, and the locally measured tumor displacement was assimilated into a biomechanical model to estimate whole-brain deformation. Our results demonstrate that the nMI re-registration pre-durotomy is critical for obtaining accurate measurement of tumor displacement, which significantly improved model response at the craniotomy when compared with stereopsis data acquired independently from the tumor registration. This automatic and computationally efficient (<2min) re-registration technique is feasible for routine clinical use in the operating room (OR).

  5. Ill-posed problem and regularization in reconstruction of radiobiological parameters from serial tumor imaging data

    NASA Astrophysics Data System (ADS)

    Chvetsov, Alevei V.; Sandison, George A.; Schwartz, Jeffrey L.; Rengan, Ramesh

    2015-11-01

    The main objective of this article is to improve the stability of reconstruction algorithms for estimation of radiobiological parameters using serial tumor imaging data acquired during radiation therapy. Serial images of tumor response to radiation therapy represent a complex summation of several exponential processes as treatment induced cell inactivation, tumor growth rates, and the rate of cell loss. Accurate assessment of treatment response would require separation of these processes because they define radiobiological determinants of treatment response and, correspondingly, tumor control probability. However, the estimation of radiobiological parameters using imaging data can be considered an inverse ill-posed problem because a sum of several exponentials would produce the Fredholm integral equation of the first kind which is ill posed. Therefore, the stability of reconstruction of radiobiological parameters presents a problem even for the simplest models of tumor response. To study stability of the parameter reconstruction problem, we used a set of serial CT imaging data for head and neck cancer and a simplest case of a two-level cell population model of tumor response. Inverse reconstruction was performed using a simulated annealing algorithm to minimize a least squared objective function. Results show that the reconstructed values of cell surviving fractions and cell doubling time exhibit significant nonphysical fluctuations if no stabilization algorithms are applied. However, after applying a stabilization algorithm based on variational regularization, the reconstruction produces statistical distributions for survival fractions and doubling time that are comparable to published in vitro data. This algorithm is an advance over our previous work where only cell surviving fractions were reconstructed. We conclude that variational regularization allows for an increase in the number of free parameters in our model which enables development of more

  6. Photoacoustic imaging of breast tumor vascularization: a comparison with MRI and histopathology

    NASA Astrophysics Data System (ADS)

    Heijblom, Michelle; Piras, Daniele; van den Engh, Frank M.; Klaase, Joost M.; Brinkhuis, Mariël.; Steenbergen, Wiendelt; Manohar, Srirang

    2013-06-01

    Breast cancer is the most common form of cancer and the leading cause of cancer death among females. Early diagnosis improves the survival chances for the disease and that is why there is an ongoing search for improved methods for visualizing breast cancer. One of the hallmarks of breast cancer is the increase in tumor vascularization that is associated with angiogenesis: a crucial factor for survival of malignancies. Photoacoustic imaging can visualize the malignancyassociated increased hemoglobin concentration with optical contrast and ultrasound resolution, without the use of ionizing radiation or contrast agents and is therefore theoretically an ideal method for breast imaging. Previous clinical studies using the Twente Photoacoustic Mammoscope (PAM), which works in forward mode using a single wavelength (1064 nm), showed that malignancies can indeed be identified in the photoacoustic imaging volume as high contrast areas. However, the specific appearance of the malignancies led to questions about the contrast mechanism in relation to tumor vascularization. In this study, the photoacoustic lesion appearance obtained with an updated version of PAM is compared with the lesion appearance on Magnetic Resonance Imaging (MRI), both in general (19 patients) and on an individual basis (7 patients). Further, in 3 patients an extended histopathology protocol is being performed in which malignancies are stained for vascularity using an endothelial antibody: CD31. The correspondence between PAM and MRI and between PAM and histopathology makes it likely that the high photoacoustic contrast at 1064 nm is indeed largely the consequence of the increased tumor vascularization.

  7. Deep, noninvasive imaging and surgical guidance of submillimeter tumors using targeted M13-stabilized single-walled carbon nanotubes.

    PubMed

    Ghosh, Debadyuti; Bagley, Alexander F; Na, Young Jeong; Birrer, Michael J; Bhatia, Sangeeta N; Belcher, Angela M

    2014-09-23

    Highly sensitive detection of small, deep tumors for early diagnosis and surgical interventions remains a challenge for conventional imaging modalities. Second-window near-infrared light (NIR2, 950-1,400 nm) is promising for in vivo fluorescence imaging due to deep tissue penetration and low tissue autofluorescence. With their intrinsic fluorescence in the NIR2 regime and lack of photobleaching, single-walled carbon nanotubes (SWNTs) are potentially attractive contrast agents to detect tumors. Here, targeted M13 virus-stabilized SWNTs are used to visualize deep, disseminated tumors in vivo. This targeted nanoprobe, which uses M13 to stably display both tumor-targeting peptides and an SWNT imaging probe, demonstrates excellent tumor-to-background uptake and exhibits higher signal-to-noise performance compared with visible and near-infrared (NIR1) dyes for delineating tumor nodules. Detection and excision of tumors by a gynecological surgeon improved with SWNT image guidance and led to the identification of submillimeter tumors. Collectively, these findings demonstrate the promise of targeted SWNT nanoprobes for noninvasive disease monitoring and guided surgery. PMID:25214538

  8. Imaging aspects of the tumor stroma with therapeutic implications

    PubMed Central

    Narunsky, Lian; Oren, Roni; Bochner, Filip; Neeman, Michal

    2013-01-01

    Cancer cells rely on extensive support from the stroma in order to survive, proliferate and invade. The tumor stroma is thus an important potential target for anti-cancer therapy. Typical changes in the stroma include a shift from the quiescence promoting- antiangiogenic extracellular matrix to a provisional matrix that promotes invasion and angiogenesis. These changes in the extracellular matrix are induced by changes in the secretion of extracellular matrix proteins and glucose amino glycans, extravasation of plasma proteins from hyperpermeable vessels and release of matrix modifying enzymes resulting in cleavage and crosslinking of matrix macromolecules. These in turn alter the rigidity of the matrix and the exposure and release of cytokines. Changes in matrix rigidity and vessel permeability affect drug delivery and mediate resistance to cytotoxic therapy. These stroma changes are brought about not only by the cancer cells, but also through the action of many cell types that are recruited by tumors including immune cells, fibroblasts and endothelial cells. Within the tumor, these normal host cells are activated resulting in loss of inhibitory and induction of cancer promoting activities. Key to the development of stroma targeted therapies, selective biomarkers were developed for specific imaging of key aspects of the tumor stroma. PMID:24134903

  9. Imaging aspects of the tumor stroma with therapeutic implications.

    PubMed

    Narunsky, Lian; Oren, Roni; Bochner, Filip; Neeman, Michal

    2014-02-01

    Cancer cells rely on extensive support from the stroma in order to survive, proliferate and invade. The tumor stroma is thus an important potential target for anti-cancer therapy. Typical changes in the stroma include a shift from the quiescence promoting-antiangiogenic extracellular matrix to a provisional matrix that promotes invasion and angiogenesis. These changes in the extracellular matrix are induced by changes in the secretion of extracellular matrix proteins and glucose amino glycans, extravasation of plasma proteins from hyperpermeable vessels and release of matrix modifying enzymes resulting in cleavage and cross-linking of matrix macromolecules. These in turn alter the rigidity of the matrix and the exposure and release of cytokines. Changes in matrix rigidity and vessel permeability affect drug delivery and mediate resistance to cytotoxic therapy. These stroma changes are brought about not only by the cancer cells, but also through the action of many cell types that are recruited by tumors including immune cells, fibroblasts and endothelial cells. Within the tumor, these normal host cells are activated resulting in loss of inhibitory and induction of cancer promoting activities. Key to the development of stroma-targeted therapies, selective biomarkers were developed for specific imaging of key aspects of the tumor stroma. PMID:24134903

  10. Hypoxia targeted carbon nanotubes as a sensitive contrast agent for photoacoustic imaging of tumors

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Aguirre, Andres; Biswal, Nrusingh C.; Pavlik, Christopher; Smith, Michael B.; Alqasemi, Umar; Li, Hai; Zhu, Quing

    2011-03-01

    Development of new and efficient contrast agents is of fundamental importance to improve detection sensitivity of smaller lesions. Within the family of nanomaterials, carbon nanotubes (CNT) not only have emerged as a new alternative and efficient transporter and translocater of therapeutic molecules but also as a photoacoustic molecular imaging agent owing to its strong optical absorption in the near-infrared region. Drugs, Antibodies and nucleic acids could functionalize the CNT and prepare an appropriate system for delivering the cargos to cells and organs. In this work, we present a novel photoacoustic contrast agent which is based on a unique hypoxic marker in the near infrared region, 2-nitroimidazole -bis carboxylic acid derivative of Indocyanine Green conjugated to single walled carbon nanotube (SWCNT-2nitroimidazole-ICG). The 2-nitroimidazole-ICG has an absorption peak at 755 nm and an extinction coefficient of 20,5222 M-1cm-1. The conjugation of this marker with SWCNT shows more than 25 times enhancement of optical absorption of carbon nanotubes in the near infrared region. This new conjugate has been optically evaluated and shows promising results for high contrast photoacoustic imaging of deeply located tumors. The conjugate specifically targets tumor hypoxia, an important indicator of tumor metabolism and tumor therapeutic response. The detection sensitivity of the new contrast agent has been evaluated in-vitro cell lines and with in-vivo tumors in mice.

  11. The role of diffusion and perfusion weighted imaging in the differential diagnosis of cerebral tumors: a review and future perspectives

    PubMed Central

    2014-01-01

    The role of conventional Magnetic Resonance Imaging (MRI) in the detection of cerebral tumors has been well established. However its excellent soft tissue visualization and variety of imaging sequences are in many cases non-specific for the assessment of brain tumor grading. Hence, advanced MRI techniques, like Diffusion-Weighted Imaging (DWI), Diffusion Tensor Imaging (DTI) and Dynamic-Susceptibility Contrast Imaging (DSCI), which are based on different contrast principles, have been used in the clinical routine to improve diagnostic accuracy. The variety of quantitative information derived from these techniques provides significant structural and functional information in a cellular level, highlighting aspects of the underlying brain pathophysiology. The present work, reviews physical principles and recent results obtained using DWI/DTI and DSCI, in tumor characterization and grading of the most common cerebral neoplasms, and discusses how the available MR quantitative data can be utilized through advanced methods of analysis, in order to optimize clinical decision making. PMID:25609475

  12. Enhancement of galaxy images for improved classification

    NASA Astrophysics Data System (ADS)

    Jenkinson, John; Grigoryan, Artyom M.; Agaian, Sos S.

    2015-03-01

    In this paper, the classification accuracy of galaxy images is demonstrated to be improved by enhancing the galaxy images. Galaxy images often contain faint regions that are of similar intensity to stars and the image background, resulting in data loss during background subtraction and galaxy segmentation. Enhancement darkens these faint regions, enabling them to be distinguished from other objects in the image and the image background, relative to their original intensities. The heap transform is employed for the purpose of enhancement. Segmentation then produces a galaxy image which closely resembles the structure of the original galaxy image, and one that is suitable for further processing and classification. 6 Morphological feature descriptors are applied to the segmented images after a preprocessing stage and used to extract the galaxy image structure for use in training the classifier. The support vector machine learning algorithm performs training and validation of the original and enhanced data, and a comparison between the classification accuracy of each data set is included. Principal component analysis is used to compress the data sets for the purpose of classification visualization and a comparison between the reduced and original feature spaces. Future directions for this research include galaxy image enhancement by various methods, and classification performed with the use of a sparse dictionary. Both future directions are introduced.

  13. FEM-based simulation of tumor growth in medical image

    NASA Astrophysics Data System (ADS)

    Luo, Shuqian; Nie, Ying

    2004-05-01

    Brain model has found wide applications in areas including surgical-path planning, image-guided surgery systems, and virtual medical environments. In comparison with the modeling of normal brain anatomy, the modeling of anatomical abnormalities appears to be rather weak. Particularly, there are considerable differences between abnormal brain images and normal brain images, due to the growth of brain tumor. In order to find the correspondence between abnormal brain images and normal ones, it is necessary to make an estimation or simulation of the brain deformation. In this paper, a deformable model of brain tissue with both geometric and physical nonlinear properties based on finite element method is presented. It is assumed that the brain tissue are nonlinearly elastic solids obeying the equations of an incompressible nonlinearly elastics neo-Hookean model. we incorporate the physical inhomogeneous of brain tissue into our FEM model. The non-linearity of the model needs to solve the deformation of the model using an iteration method. The Updated Lagrange for iteration is used. To assure the convergence of iteration, we adopt the fixed arc length method. This model has advantages over those linear models in its more real tissue properties and its capability of simulating more serious brain deformation. The inclusion of second order displacement items into the balance and geometry functions allows for the estimation of more serious brain deformation. We referenced the model presented by Stelios K so as to ascertain the initial position of tumor as well as our tumor model definition. Furthermore, we expend it from 2-D to 3-D and simplify the calculation process.

  14. Digital holographic optical coherence imaging of tumor tissue

    NASA Astrophysics Data System (ADS)

    Jeong, Kwan; Turek, John J.; Nolte, David D.

    2006-02-01

    Holographic Optical Coherence Imaging (OCI) uses spatial heterodyne detection in direct analogy with the temporal heterodyne detection of time-domain OCT. The spatial demodulator can be a sensitive dynamic holographic film or can be a CCD array placed directly at the hologram plane. We show that a digital hologram captured at the Fourier plane requires only a simple 2D inverse FFT of the digital hologram to compute the real image and its conjugate. Our recording on the optical Fourier plane has an advantage for diffuse targets because the intensity distribution of diffuse targets is relatively uniform at the Fourier plane and hence uses the full dynamic range of CCD camera. We applied this technique to human liver tumor spheroids and produced depth-resolved images to depth of 1.4 mm.

  15. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    SciTech Connect

    Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  16. In vivo imaging of tumor angiogenesis using fluorescence confocal videomicroscopy.

    PubMed

    Fitoussi, Victor; Faye, Nathalie; Chamming's, Foucauld; Clement, Olivier; Cuenod, Charles-Andre; Fournier, Laure S

    2013-01-01

    Fibered confocal fluorescence in vivo imaging with a fiber optic bundle uses the same principle as fluorescent confocal microscopy. It can excite fluorescent in situ elements through the optical fibers, and then record some of the emitted photons, via the same optical fibers. The light source is a laser that sends the exciting light through an element within the fiber bundle and as it scans over the sample, recreates an image pixel by pixel. As this scan is very fast, by combining it with dedicated image processing software, images in real time with a frequency of 12 frames/sec can be obtained. We developed a technique to quantitatively characterize capillary morphology and function, using a confocal fluorescence videomicroscopy device. The first step in our experiment was to record 5 sec movies in the four quadrants of the tumor to visualize the capillary network. All movies were processed using software (ImageCell, Mauna Kea Technology, Paris France) that performs an automated segmentation of vessels around a chosen diameter (10 μm in our case). Thus, we could quantify the 'functional capillary density', which is the ratio between the total vessel area and the total area of the image. This parameter was a surrogate marker for microvascular density, usually measured using pathology tools. The second step was to record movies of the tumor over 20 min to quantify leakage of the macromolecular contrast agent through the capillary wall into the interstitium. By measuring the ratio of signal intensity in the interstitium over that in the vessels, an 'index leakage' was obtained, acting as a surrogate marker for capillary permeability. PMID:24056503

  17. In vivo Imaging of Tumor Angiogenesis using Fluorescence Confocal Videomicroscopy

    PubMed Central

    Fitoussi, Victor; Faye, Nathalie; Chamming's, Foucauld; Clement, Olivier; Cuenod, Charles-Andre; Fournier, Laure S.

    2013-01-01

    Fibered confocal fluorescence in vivo imaging with a fiber optic bundle uses the same principle as fluorescent confocal microscopy. It can excite fluorescent in situ elements through the optical fibers, and then record some of the emitted photons, via the same optical fibers. The light source is a laser that sends the exciting light through an element within the fiber bundle and as it scans over the sample, recreates an image pixel by pixel. As this scan is very fast, by combining it with dedicated image processing software, images in real time with a frequency of 12 frames/sec can be obtained. We developed a technique to quantitatively characterize capillary morphology and function, using a confocal fluorescence videomicroscopy device. The first step in our experiment was to record 5 sec movies in the four quadrants of the tumor to visualize the capillary network. All movies were processed using software (ImageCell, Mauna Kea Technology, Paris France) that performs an automated segmentation of vessels around a chosen diameter (10 μm in our case). Thus, we could quantify the 'functional capillary density', which is the ratio between the total vessel area and the total area of the image. This parameter was a surrogate marker for microvascular density, usually measured using pathology tools. The second step was to record movies of the tumor over 20 min to quantify leakage of the macromolecular contrast agent through the capillary wall into the interstitium. By measuring the ratio of signal intensity in the interstitium over that in the vessels, an 'index leakage' was obtained, acting as a surrogate marker for capillary permeability. PMID:24056503

  18. Evaluation of high intensity focused ultrasound ablation of prostate tumor with hyperpolarized 13C imaging biomarkers

    NASA Astrophysics Data System (ADS)

    Lee, Jessie E.; Diederich, Chris J.; Salgaonkar, Vasant A.; Bok, Robert; Taylor, Andrew G.; Kurhanewicz, John

    2015-03-01

    Real-time hyperpolarized (HP) 13C MR can be utilized during high-intensity focal ultrasound (HIFU) therapy to improve treatment delivery strategies, provide treatment verification, and thus reduce the need for more radical therapies for lowand intermediate-risk prostate cancers. The goal is to develop imaging biomarkers specific to thermal therapies of prostate cancer using HIFU, and to predict the success of thermal coagulation and identify tissues potentially sensitized to adjuvant treatment by sub-ablative hyperthermic heat doses. Mice with solid prostate tumors received HIFU treatment (5.6 MHz, 160W/cm2, 60 s), and the MR imaging follow-ups were performed on a wide-bore 14T microimaging system. 13C-labeled pyruvate and urea were used to monitor tumor metabolism and perfusion accordingly. After treatment, the ablated tumor tissue had a loss in metabolism and perfusion. In the regions receiving sub-ablative heat dose, a timedependent change in metabolism and perfusion was observed. The untreated regions behaved as a normal untreated TRAMP prostate tumor would. This promising preliminary study shows the potential of using 13C MR imaging as biomarkers of HIFU/thermal therapies.

  19. Caged [(18)F]FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography.

    PubMed

    Flavell, Robert R; Truillet, Charles; Regan, Melanie K; Ganguly, Tanushree; Blecha, Joseph E; Kurhanewicz, John; VanBrocklin, Henry F; Keshari, Kayvan R; Chang, Christopher J; Evans, Michael J; Wilson, David M

    2016-01-20

    Solid tumors are hypoxic with altered metabolism, resulting in secretion of acids into the extracellular matrix and lower relative pH, a feature associated with local invasion and metastasis. Therapeutic and diagnostic agents responsive to this microenvironment may improve tumor-specific delivery. Therefore, we pursued a general strategy whereby caged small-molecule drugs or imaging agents liberate their parent compounds in regions of low interstitial pH. In this manuscript, we present a new acid-labile prodrug method based on the glycosylamine linkage, and its application to a class of positron emission tomography (PET) imaging tracers, termed [(18)F]FDG amines. [(18)F]FDG amines operate via a proposed two-step mechanism, in which an acid-labile precursor decomposes to form the common radiotracer 2-deoxy-2-[(18)F]fluoro-d-glucose, which is subsequently accumulated by glucose avid cells. The rate of decomposition of [(18)F]FDG amines is tunable in a systematic fashion, tracking the pKa of the parent amine. In vivo, a 4-phenylbenzylamine [(18)F]FDG amine congener showed greater relative accumulation in tumors over benign tissue, which could be attenuated upon tumor alkalinization using previously validated models, including sodium bicarbonate treatment, or overexpression of carbonic anhydrase. This new class of PET tracer represents a viable approach for imaging acidic interstitial pH with potential for clinical translation. PMID:26649808

  20. Curcumin-incorporated albumin nanoparticles and its tumor image

    NASA Astrophysics Data System (ADS)

    Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

    2015-01-01

    Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

  1. [Importance of rapid MR imaging for tumor diagnosis in the area of the kidneys and adrenals].

    PubMed

    Friedmann, G; Krestin, G P; Engelking, R; Vorreuther, R

    1988-02-01

    Gradient-echo pulse sequences with fast acquisition times permit examinations in short breath-holding intervals. In this way an improvement of MR imaging of upper abdominal organs can be expected. In 41 patients with space-occupying lesions of kidneys and adrenals, influence of external parameter variations on resulting contrasts was analyzed and results were compared to other imaging methods. Gradient-echo sequences demonstrated a high sensitivity in detection of tumorous lesions of kidneys and adrenals, the specificity being similar to that of CT. Further differentiation was only possible by performing dynamic perfusion studies using paramagnetic contrast agents. PMID:2831575

  2. Studying tumor metastasis by in vivo imaging and flow cytometer

    NASA Astrophysics Data System (ADS)

    Wei, Xunbin; Guo, Jin; Liu, Guangda; Li, Yan; Chen, Yun; Zhang, Li; Tan, Yuan; Chen, Tong; Gu, Zhenqin; Wang, Chen

    2009-02-01

    Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every year. This ranges from 15,000 cases in the United States to more than a 250,000 in China. About 80% of people with primary liver cancer are male. Although two-thirds of people have advanced liver disease when they seek medical help, one third of the patients have cancer that has not progressed beyond the liver. Primary liver cancer (hepatocellular carcinoma, or HCC) is associated with liver cirrhosis 60-80% of the time. HCC may metastasize to the lung, bones, kidney, and many other organs. Surgical resection, liver transplantation, chemotherapy and radiation therapy are the foundation of current HCC therapies. However the outcomes are poor-the survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of HCC cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern liver tumor cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess liver tumor cell spreading and the circulation kinetics of liver tumor cells. A real-time quantitative monitoring of circulating liver tumor cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  3. Improvement of image quality by polarization mixing

    NASA Astrophysics Data System (ADS)

    Kasahara, Ryosuke; Itoh, Izumi; Hirai, Hideaki

    2014-03-01

    Information about the polarization of light is valuable because it contains information about the light source illuminating an object, the illumination angle, and the object material. However, polarization information strongly depends on the direction of the light source, and it is difficult to use a polarization image with various recognition algorithms outdoors because the angle of the sun varies. We propose an image enhancement method for utilizing polarization information in many such situations where the light source is not fixed. We take two approaches to overcome this problem. First, we compute an image that is the combination of a polarization image and the corresponding brightness image. Because of the angle of the light source, the polarization contains no information about some scenes. Therefore, it is difficult to use only polarization information in any scene for applications such as object detection. However, if we use a combination of a polarization image and a brightness image, the brightness image can complement the lack of scene information. The second approach is finding features that depend less on the direction of the light source. We propose a method for extracting scene features based on a calculation of the reflection model including polarization effects. A polarization camera that has micro-polarizers on each pixel of the image sensor was built and used for capturing images. We discuss examples that demonstrate the improved visibility of objects by applying our proposed method to, e.g., the visibility of lane markers on wet roads.

  4. Blocking EGFR in the liver improves the tumor-to-liver uptake ratio of radiolabeled EGF.

    PubMed

    Kareem, Heewa; Sandström, Karl; Elia, Ronny; Gedda, Lars; Anniko, Matti; Lundqvist, Hans; Nestor, Marika

    2010-04-01

    Overexpression of epidermal growth factor receptor (EGFR) in several types of malignant tumors correlates with disease progression. EGFR could, therefore, be an excellent candidate for targeted radionuclide diagnostics. However, the high natural expression of EGFR in the liver may be problematic. The aim of this study was to improve the tumor-to-liver ratio of radiolabeled epidermal growth factor (EGF) by blocking its uptake by the liver with a nonradiolabeled EGFR-targeting molecule in tumor-bearing mice. Intraperitoneally injected nonradiolabeled EGF was first evaluated as a blocking agent, preadministered at various time intervals before intravenous injection of (125)I-labeled EGF. The anti-EGFR Affibody molecule (Z(EGFR:955))(2) was then assessed as a blocking agent of (111)In-labeled EGF in a dual isotope study (50, 100, and 200 microg, preadministered 30 or 60 min before (111)In-EGF). The 30-min preadministration of nonradiolabeled EGF significantly decreased (125)I-EGF uptake in the liver, whereas uptake in the tumor remained unchanged. Furthermore, preadministration of only 50 microg (Z(EGFR:955))(2) as a blocking agent 30 min before the (111)In-EGF decreased the uptake of (111)In-EGF by the liver and increased its uptake by the tumor, thereby increasing the tumor-to-liver ratio sixfold. We conclude that the Affibody molecule (Z(EGFR:955))(2) shows promise as a blocking agent that could enhance the outcome of radionuclide-based EGFR-expressing tumor diagnostics and imaging. PMID:20358420

  5. Necrosis targeted radiotherapy with iodine-131-labeled hypericin to improve anticancer efficacy of vascular disrupting treatment in rabbit VX2 tumor models

    PubMed Central

    Shao, Haibo; Zhang, Jian; Sun, Ziping; Chen, Feng; Dai, Xu; Li, Yaming; Ni, Yicheng; Xu, Ke

    2015-01-01

    A viable rim of tumor cells surrounding central necrosis always exists and leads to tumor recurrence after vascular disrupting treatment (VDT). A novel necrosis targeted radiotherapy (NTRT) using iodine-131-labeled hypericin (131I-Hyp) was specifically designed to treat viable tumor rim and improve tumor control after VDT in rabbit models of multifocal VX2 tumors. NTRT was administered 24 hours after VDT. Tumor growth was significantly slowed down by NTRT with a smaller tumor volume and a prolonged tumor doubling time (14.4 vs. 5.7 days), as followed by in vivo magnetic resonance imaging over 12 days. The viable tumor rims were well inhibited in NTRT group compared with single VDT control group, as showed on tumor cross sections at day 12 (1 vs. 3.7 in area). High targetability of 131I-Hyp to tumor necrosis was demonstrated by in vivo SPECT as high uptake in tumor regions lasting over 9 days with 4.26 to 98 times higher radioactivity for necrosis versus the viable tumor and other organs by gamma counting, and with ratios of 7.7–11.7 and 10.5–13.7 for necrosis over peri-tumor tissue by autoradiography and fluorescence microscopy, respectively. In conclusion, NTRT improved the anticancer efficacy of VDT in rabbits with VX2 tumors. PMID:26036625

  6. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  7. Nebulized gadolinium-based nanoparticles: a theranostic approach for lung tumor imaging and radiosensitization.

    PubMed

    Dufort, Sandrine; Bianchi, Andrea; Henry, Maxime; Lux, François; Le Duc, Géraldine; Josserand, Véronique; Louis, Cédric; Perriat, Pascal; Crémillieux, Yannick; Tillement, Olivier; Coll, Jean-Luc

    2015-01-14

    Lung cancer is the most common and most fatal cancer worldwide. Thus, improving early diagnosis and therapy is necessary. Previously, gadolinium-based ultra-small rigid platforms (USRPs) were developed to serve as multimodal imaging probes and as radiosensitizing agents. In addition, it was demonstrated that USRPs can be detected in the lungs using ultrashort echo-time magnetic resonance imaging (UTE-MRI) and fluorescence imaging after intrapulmonary administration in healthy animals. The goal of the present study is to evaluate their theranostic properties in mice with bioluminescent orthotopic lung cancer, after intrapulmonary nebulization or conventional intravenous administration. It is found that lung tumors can be detected non-invasively using fluorescence tomography or UTE-MRI after nebulization of USRPs, and this is confirmed by histological analysis of the lung sections. The deposition of USRPs around the tumor nodules is sufficient to generate a radiosensitizing effect when the mice are subjected to a single dose of 10 Gy conventional radiation one day after inhalation (mean survival time of 112 days versus 77 days for irradiated mice without USRPs treatment). No apparent systemic toxicity or induction of inflammation is observed. These results demonstrate the theranostic properties of USRPs for the multimodal detection of lung tumors and improved radiotherapy after nebulization. PMID:25201285

  8. Imaging of tumor clones with differential liver colonization

    PubMed Central

    Oshima, Go; Wightman, Sean C.; Uppal, Abhineet; Stack, Melinda E.; Pitroda, Sean P.; Oskvarek, Jonathan J.; Huang, Xiaona; Posner, Mitchell C.; Hellman, Samuel; Weichselbaum, Ralph R.; Khodarev, Nikolai N.

    2015-01-01

    We present a model of hepatic colorectal metastases which represents monoclonal cell lines double-labeled by luciferase and tdTomato. These cells form liver metastasis in varying numbers and patterns similar to those observed in patients. Using in vivo and ex vivo luminescent and fluorescent imaging we determine the growth kinetics and clonogenic frequency of tumor cells colonizing liver. Molecular profiling detected stable expressional differences between clones consistent with their phenotypes. The data indicate that clinically relevant phenotypes of liver metastases can be modeled in vivo. PMID:26094901

  9. Non-Rigid Registration of Liver CT Images for CT-Guided Ablation of Liver Tumors.

    PubMed

    Luu, Ha Manh; Klink, Camiel; Niessen, Wiro; Moelker, Adriaan; Walsum, Theo van

    2016-01-01

    CT-guided percutaneous ablation for liver cancer treatment is a relevant technique for patients not eligible for surgery and with tumors that are inconspicuous on US imaging. The lack of real-time imaging and the use of a limited amount of CT contrast agent make targeting the tumor with the needle challenging. In this study, we evaluate a registration framework that allows the integration of diagnostic pre-operative contrast enhanced CT images and intra-operative non-contrast enhanced CT images to improve image guidance in the intervention. The liver and tumor are segmented in the pre-operative contrast enhanced CT images. Next, the contrast enhanced image is registered to the intra-operative CT images in a two-stage approach. First, the contrast-enhanced diagnostic image is non-rigidly registered to a non-contrast enhanced image that is conventionally acquired at the start of the intervention. In case the initial registration is not sufficiently accurate, a refinement step is applied using non-rigid registration method with a local rigidity term. In the second stage, the intra-operative CT-images that are used to check the needle position, which often consist of only a few slices, are registered rigidly to the intra-operative image that was acquired at the start of the intervention. Subsequently, the diagnostic image is registered to the current intra-operative image, using both transformations, this allows the visualization of the tumor region extracted from pre-operative data in the intra-operative CT images containing needle. The method is evaluated on imaging data of 19 patients at the Erasmus MC. Quantitative evaluation is performed using the Dice metric, mean surface distance of the liver border and corresponding landmarks in the diagnostic and the intra-operative images. The registration of the diagnostic CT image to the initial intra-operative CT image did not require a refinement step in 13 cases. For those cases, the resulting registration had a Dice

  10. Erythropoietin improves the accumulation and therapeutic effects of carboplatin by enhancing tumor vascularization and perfusion.

    PubMed

    Doleschel, Dennis; Rix, Anne; Arns, Susanne; Palmowski, Karin; Gremse, Felix; Merkle, Ruth; Salopiata, Florian; Klingmüller, Ursula; Jarsch, Michael; Kiessling, Fabian; Lederle, Wiltrud

    2015-01-01

    Recombinant human erythropoietin (rhuEpo) is currently under debate for the treatment of chemotherapy-induced anemia due to clinical trials showing adverse effects in Epo-treated patients and the discovery of the erythropoietin-receptor (EpoR) in tumor and endothelial cells. Here, using Epo-Cy5.5 as theranostic near-infrared fluorescent probe we analyzed the effects of rhuEpo as co-medication to carboplatin in non-small-cell-lung-cancer (NSCLC)-xenografts with different tumor cell EpoR-expression (H838 ~8-fold higher than A549). Nude mice bearing subcutaneous A549 and H838 NSCLC-xenografts received either only carboplatin or carboplatin and co-medication of rhuEpo in two different doses. Tumor sizes and relative blood volumes (rBV) were longitudinally measured by 3D-contrast-enhanced ultrasound (3D-US). Tumoral EpoR-levels were determined by combined fluorescence molecular tomography (FMT)/ micro computed tomography (µCT) hybrid imaging. We found that rhuEpo predominantly acted on the tumor endothelium. In both xenografts, rhuEpo co-medication significantly increased vessel densities, diameters and the amount of perfused vessels. Accordingly, rhuEpo induced EpoR-phoshorylation and stimulated proliferation of endothelial cells. However, compared with solely carboplatin-treated tumors, tumor growth was significantly slower in the groups co-medicated with rhuEpo. This is explained by the Epo-mediated vascular remodeling leading to improved drug delivery as obvious by a more than 2-fold higher carboplatin accumulation and significantly enhanced tumor apoptosis. In addition, co-medication of rhuEpo reduced tumor hypoxia and diminished intratumoral EpoR-levels which continuously increased during carboplatin (Cp) -treatment. These findings suggest that co-medication of rhuEpo in well balanced doses can be used to improve the accumulation of anticancer drugs. Doses and indications may be personalized and refined using theranostic EpoR-probes. PMID:26000061