Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors.

PubMed

Skelton, Rhys J P; Khoja, Suhail; Almeida, Shone; Rapacchi, Stanislas; Han, Fei; Engel, James; Zhao, Peng; Hu, Peng; Stanley, Edouard G; Elefanty, Andrew G; Kwon, Murray; Elliott, David A; Ardehali, Reza

2016-01-01

Given the limited regenerative capacity of the heart, cellular therapy with stem cell-derived cardiac cells could be a potential treatment for patients with heart disease. However, reliable imaging techniques to longitudinally assess engraftment of the transplanted cells are scant. To address this issue, we used ferumoxytol as a labeling agent of human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) to facilitate tracking by magnetic resonance imaging (MRI) in a large animal model. Differentiating hESCs were exposed to ferumoxytol at different time points and varying concentrations. We determined that treatment with ferumoxytol at 300 μg/ml on day 0 of cardiac differentiation offered adequate cell viability and signal intensity for MRI detection without compromising further differentiation into definitive cardiac lineages. Labeled hESC-CPCs were transplanted by open surgical methods into the left ventricular free wall of uninjured pig hearts and imaged both ex vivo and in vivo. Comprehensive T2*-weighted images were obtained immediately after transplantation and 40 days later before termination. The localization and dispersion of labeled cells could be effectively imaged and tracked at days 0 and 40 by MRI. Thus, under the described conditions, ferumoxytol can be used as a long-term, differentiation-neutral cell-labeling agent to track transplanted hESC-CPCs in vivo using MRI. The development of a safe and reproducible in vivo imaging technique to track the fate of transplanted human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) is a necessary step to clinical translation. An iron oxide nanoparticle (ferumoxytol)-based approach was used for cell labeling and subsequent in vivo magnetic resonance imaging monitoring of hESC-CPCs transplanted into uninjured pig hearts. The present results demonstrate the use of ferumoxytol labeling and imaging techniques in tracking the location and dispersion of cell grafts, highlighting its utility in future cardiac stem cell therapy trials. ©AlphaMed Press.

Poly (dopamine) coated superparamagnetic iron oxide nanocluster for noninvasive labeling, tracking, and targeted delivery of adipose tissue-derived stem cells

PubMed Central

Liao, Naishun; Wu, Ming; Pan, Fan; Lin, Jiumao; Li, Zuanfang; Zhang, Da; Wang, Yingchao; Zheng, Youshi; Peng, Jun; Liu, Xiaolong; Liu, Jingfeng

2016-01-01

Tracking and monitoring of cells in vivo after transplantation can provide crucial information for stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be an effective and non-invasive technique for cell tracking in living bodies. However, commercial superparamagnetic iron oxide nanoparticles (SPIONs) applied to label cells suffer from shortages such as potential toxicity, low labeling efficiency, and low contrast enhancing. Herein, the adipose tissue-derived stem cells (ADSCs) were efficiently labeled with SPIONs coated with poly (dopamine) (SPIONs cluster@PDA), without affecting their viability, proliferation, apoptosis, surface marker expression, as well as their self-renew ability and multi-differentiation potential. The labeled cells transplanted into the mice through tail intravenous injection exhibited a negative enhancement of the MRI signal in the damaged liver-induced by carbon tetrachloride, and subsequently these homed ADSCs with SPIONs cluster@PDA labeling exhibited excellent repair effects to the damaged liver. Moreover, the enhanced target-homing to tissue of interest and repair effects of SPIONs cluster@PDA-labeled ADSCs could be achieved by use of external magnetic field in the excisional skin wound mice model. Therefore, we provide a facile, safe, noninvasive and sensitive method for external magnetic field targeted delivery and MRI based tracking of transplanted cells in vivo. PMID:26728448

Magnetic resonance imaging with superparamagnetic iron oxide fails to track the long-term fate of mesenchymal stem cells transplanted into heart.

PubMed

Ma, Ning; Cheng, Huaibing; Lu, Minjie; Liu, Qiong; Chen, Xiuyu; Yin, Gang; Zhu, Hao; Zhang, Lianfeng; Meng, Xianmin; Tang, Yue; Zhao, Shihua

2015-03-12

MRI for in vivo stem cell tracking remains controversial. Here we tested the hypothesis that MRI can track the long-term fate of the superparamagnetic iron oxide (SPIO) nanoparticles labelled mesenchymal stem cells (MSCs) following intramyocardially injection in AMI rats. MSCs (1 × 10(6)) from male rats doubly labeled with SPIO and DAPI were injected 2 weeks after myocardial infarction. The control group received cell-free media injection. In vivo serial MRI was performed at 24 hours before cell delivery (baseline), 3 days, 1, 2, and 4 weeks after cell delivery, respectively. Serial follow-up MRI demonstrated large persistent intramyocardial signal-voids representing SPIO during the follow-up of 4 weeks, and MSCs did not moderate the left ventricular dysfunction. The TUNEL analysis confirmed that MSCs engrafted underwent apoptosis. The histopathological studies revealed that the site of cell injection was infiltrated by inflammatory cells progressively and the iron-positive cells were macrophages identified by CD68 staining, but very few or no DAPI-positive stem cells at 4 weeks after cells transplantation. The presence of engrafted cells was confirmed by real-time PCR, which showed that the amount of Y-chromosome-specific SRY gene was consistent with the results. MRI may not reliably track the long-term fate of SPIO-labeled MSCs engraftment in heart.

In Vivo Cytometry of Antigen-Specific T Cells Using 19F MRI

PubMed Central

Srinivas, Mangala; Turner, Michael S.; Janjic, Jelena M.; Morel, Penelope A.; Laidlaw, David H.; Ahrens, Eric T.

2009-01-01

Noninvasive methods to image the trafficking of phenotypically defined immune cells are paramount as we attempt to understand adaptive immunity. A 19F MRI-based methodology for tracking and quantifying cells of a defined phenotype is presented. These methods were applied to a murine inflammation model using antigen-specific T cells. The T cells that were intracellularly labeled ex vivo with a perfluoropolyether (PFPE) nanoemulsion and cells were transferred to a host receiving a localized inoculation of antigen. Longitudinal 19F MRI over 21 days revealed a dynamic accumulation and clearance of T cells in the lymph node (LN) draining the antigen. The apparent T-cell numbers were calculated in the LN from the time-lapse 19F MRI data. The effect of in vivo T-cell division on the 19F MRI cell quantification accuracy was investigated using fluorescence assays. Overall, in vivo cytometry using PFPE labeling and 19F MRI is broadly applicable to studies of whole-body cell biodistribution. PMID:19585593

Tracking cells implanted into cynomolgus monkeys (Macaca fascicularis) using MRI

PubMed Central

Ito-Fujishiro, Yasuyo; Koie, Hiroshi; Shibata, Hiroaki; Okabayashi, Sachi; Katakai, Yuko; Ohno, Chieko; Kanayama, Kiichi; Yasutomi, Yasuhiro; Ageyama, Naohide

2016-01-01

Regenerative therapy with stem cell transplantation is used to treat various diseases such as coronary syndrome and Buerger’s disease. For instance, stem-cell transplantation into the infarcted myocardium is an innovative and promising strategy for treating heart failure due to ischemic heart disease. Basic studies using small animals have shown that transplanted cells improve blood flow in the infarcted region. Magnetic resonance imaging (MRI) can noninvasively identify and track transplanted cells labeled with superparamagnetic iron oxide (SPIO). Although clinical regenerative therapies have been clinically applied to patients, the fate of implanted cells remains unknown. In addition, follow-up studies have shown that some adverse events can occur after recovery. Therefore, the present study evaluated the ability of MRI using a 3T scanner to track implanted peripheral blood mononuclear cells labeled with SPIO on days 0 and 7 after intramuscular (i.m.) and intravenous (i.v.) injection into a cynomolgus monkey. Labeled cells were visualized at the liver and triceps surae muscle on MR images using T1- and T2-weighted sequences and histologically localized by Prussian blue staining. The transplanted cells were tracked without abnormal clinical manifestations throughout this study. Hence, MRI of cynomolgus monkey transplanted SPIO-labeled cells is a safe and efficient method of tracking labeled cells that could help to determine the mechanisms involved in regenerative therapy. PMID:27062993

Tracking stem cells in tissue-engineered organs using magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Thanh, NguyêN. Thi Kim

2013-11-01

The use of human stem cells (SCs) in tissue engineering holds promise in revolutionising the treatment of numerous diseases. There is a pressing need to comprehend the distribution, movement and role of SCs once implanted onto scaffolds. Nanotechnology has provided a platform to investigate this through the development of inorganic magnetic nanoparticles (MNPs). MNPs can be used to label and track SCs by magnetic resonance imaging (MRI) since this clinically available imaging modality has high spatial resolution. In this review, we highlight recent applications of iron oxide and gadolinium based MNPs in SC labelling and MRI; and offer novel considerations for their future development.

A unique 19F MRI agent for the tracking of non phagocytic cells in vivo.

PubMed

Moonshi, Shehzahdi S; Zhang, Cheng; Peng, Hui; Puttick, Simon; Rose, Stephen; Fisk, Nicholas M; Bhakoo, Kishore; Stringer, Brett W; Qiao, Greg G; Gurr, Paul A; Whittaker, Andrew K

2018-05-03

There is currently intense interest in new methods for understanding the fate of therapeutically-relevant cells, such as mesenchymal stem cells (MSCs). The absence of a confounding background signal and consequent unequivocal assignment makes 19F MRI one of the most attractive modalities for the tracking of injected cells in vivo. We describe here the synthesis of novel partly-fluorinated polymeric nanoparticles with small size and high fluorine content as MRI agents. The polymers, constructed from perfluoropolyether methacrylate (PFPEMA) and oligo(ethylene glycol) methacrylate (OEGMA) have favourable cell uptake profiles and excellent MRI performance. To facilitate cell studies the polymer was further conjugated with a fluorescent dye creating a dual-modal imaging agent. The efficacy of labelling of MSCs was assessed using 19F NMR, flow cytometry and confocal microscopy. The labelling efficiency of 2.6 ± 0.1 × 1012 19F atoms per cell, and viability of >90% demonstrates high uptake and good tolerance by the cells. This loading translates to a minimum 19F MRI detection sensitivity of ∼7.4 × 103 cells per voxel. Importantly, preliminary in vivo data demonstrate that labelled cells can be readily detected within a short acquisition scan period (12 minutes). Hence, these copolymers show outstanding potential for 19F MRI cellular tracking and for quantification of non-phagocytic and therapeutically-relevant cells in vivo.

Non-invasive imaging using reporter genes altering cellular water permeability

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

High MRI performance fluorescent mesoporous silica-coated magnetic nanoparticles for tracking neural progenitor cells in an ischemic mouse model.

PubMed

Zhang, Lu; Wang, Yao; Tang, Yaohui; Jiao, Zheng; Xie, Chengying; Zhang, Haijiao; Gu, Ping; Wei, Xunbin; Yang, Guo-Yuan; Gu, Hongchen; Zhang, Chunfu

2013-05-21

Multifunctional probes with high MRI sensitivity and high efficiency for cell labeling are desirable for MR cell imaging. Herein, we have fabricated fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (fmSiO4@SPIONs) for neural progenitor cell (C17.2) MR imaging. FmSiO4@SPIONs were discrete and uniform in size, and had a clear core-shell structure. The magnetic core size was about 10 nm and the fluorescent mesoporous silica coating layer was around 20 nm. Compared with fluorescent dense silica-coated SPIONs (fdSiO4@SPIONs) with a similar size, fmSiO4@SPIONs demonstrated higher MR sensitivity and cell labeling efficiency. When implanted into the right hemisphere of stroke mice, contralateral to the ischemic territory, a small amount of labeled cells were able to be tracked migrating to the lesion sites using a clinical MRI scanner (3 T). More impressively, even when administered intravenously, the labeled cells could also be monitored homing to the ischemic area. MRI observations were corroborated by histological studies of the brain tissues. Our study demonstrated that fmSiO4@SPIONs are highly effective for cell imaging and hold great promise for MRI cell tracking in future.

Endowing carbon nanotubes with superparamagnetic properties: applications for cell labeling, MRI cell tracking and magnetic manipulations.

PubMed

Lamanna, Giuseppe; Garofalo, Antonio; Popa, Gabriela; Wilhelm, Claire; Bégin-Colin, Sylvie; Felder-Flesch, Delphine; Bianco, Alberto; Gazeau, Florence; Ménard-Moyon, Cécilia

2013-05-21

Coating of carbon nanotubes (CNTs) with magnetic nanoparticles (NPs) imparts novel magnetic, optical, and thermal properties with potential applications in the biomedical domain. Multi-walled CNTs have been decorated with iron oxide superparamagnetic NPs. Two different approaches have been investigated based on ligand exchange or "click chemistry". The presence of the NPs on the nanotube surface allows conferring magnetic properties to CNTs. We have evaluated the potential of the NP/CNT hybrids as a contrast agent for magnetic resonance imaging (MRI) and their interactions with cells. The capacity of the hybrids to magnetically monitor and manipulate cells has also been investigated. The NP/CNTs can be manipulated by a remote magnetic field with enhanced contrast in MRI. They are internalized into tumor cells without showing cytotoxicity. The labeled cells can be magnetically manipulated as they display magnetic mobility and are detected at a single cell level through high resolution MRI.

Imaging transplanted stem cells in real time using an MRI dual-contrast method

PubMed Central

Ngen, Ethel J.; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-01-01

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies. PMID:26330231

Imaging transplanted stem cells in real time using an MRI dual-contrast method.

PubMed

Ngen, Ethel J; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-09-02

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.

Synthetic and biogenic magnetite nanoparticles for tracking of stem cells and dendritic cells

NASA Astrophysics Data System (ADS)

Schwarz, Sebastian; Fernandes, Fabiana; Sanroman, Laura; Hodenius, Michael; Lang, Claus; Himmelreich, Uwe; Schmitz-Rode, Thomas; Schueler, Dirk; Hoehn, Mathias; Zenke, Martin; Hieronymus, Thomas

2009-05-01

Accurate delivery of cells to target organs is critical for success of cell-based therapies with stem cells or immune cells such as antigen-presenting dendritic cells (DC). Labeling with contrast agents before implantation provides a powerful means for monitoring cellular migration using magnetic resonance imaging (MRI). In this study, we investigated the uptake of fully synthesized or bacterial magnetic nanoparticles (MNPs) into hematopoietic Flt3 + stem cells and DC from mouse bone marrow. We show that (i) uptake of both synthetic and biogenic nanoparticles into cells endow magnetic activity and (ii) low numbers of MNP-loaded cells are readily detected by MRI.

A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI.

PubMed

Liu, Li; Tseng, Lanya; Ye, Qing; Wu, Yijen L; Bain, Daniel J; Ho, Chien

2016-05-18

Mesenchymal stem cells (MSCs) are among the major stem cells used for cell therapy and regenerative medicine. In-vivo cell-tracking by magnetic resonance imaging (MRI) is crucial for regenerative medicine, allowing verification that the transplanted cells reach the targeted sites. Cellular MRI combined with superparamagnetic iron-oxide (SPIO) contrast agents is an effective cell-tracking method. Here, we are reporting a new "bio-mimicry" method by making use of the "in-vivo environment" of MSCs to prepare native MSCs, so that (i) the phagocytic activity of cultured MSCs can be recovered and expanded MSCs can be ex-vivo labeled with Ferumoxytol, which is currently the only FDA approved SPIO nanoparticles for human use. Using our new method, 7-day cultured MSCs regain the capability to take up Ferumoxytol and exhibit an intracellular iron concentration of 2.50 ± 0.50 pg/MSC, comparable to that obtained by using Ferumoxytol-heparin-protamine nanocomplex; and (ii) cells can be re-sized to more native size, reducing from 32.0 ± 7.2 μm to 19.5 ± 5.2 μm. Our method can be very useful for expanding MSCs and labeling with Ferumoxytol, without the need for transfection agents and/or electroporation, allowing cell-tracking by MRI in both pre-clinical and clinical studies.

A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI

PubMed Central

Liu, Li; Tseng, Lanya; Ye, Qing; Wu, Yijen L.; Bain, Daniel J.; Ho, Chien

2016-01-01

Mesenchymal stem cells (MSCs) are among the major stem cells used for cell therapy and regenerative medicine. In-vivo cell-tracking by magnetic resonance imaging (MRI) is crucial for regenerative medicine, allowing verification that the transplanted cells reach the targeted sites. Cellular MRI combined with superparamagnetic iron-oxide (SPIO) contrast agents is an effective cell-tracking method. Here, we are reporting a new “bio-mimicry” method by making use of the “in-vivo environment” of MSCs to prepare native MSCs, so that (i) the phagocytic activity of cultured MSCs can be recovered and expanded MSCs can be ex-vivo labeled with Ferumoxytol, which is currently the only FDA approved SPIO nanoparticles for human use. Using our new method, 7-day cultured MSCs regain the capability to take up Ferumoxytol and exhibit an intracellular iron concentration of 2.50 ± 0.50 pg/MSC, comparable to that obtained by using Ferumoxytol-heparin-protamine nanocomplex; and (ii) cells can be re-sized to more native size, reducing from 32.0 ± 7.2 μm to 19.5 ± 5.2 μm. Our method can be very useful for expanding MSCs and labeling with Ferumoxytol, without the need for transfection agents and/or electroporation, allowing cell-tracking by MRI in both pre-clinical and clinical studies. PMID:27188664

High MRI performance fluorescent mesoporous silica-coated magnetic nanoparticles for tracking neural progenitor cells in an ischemic mouse model

NASA Astrophysics Data System (ADS)

Zhang, Lu; Wang, Yao; Tang, Yaohui; Jiao, Zheng; Xie, Chengying; Zhang, Haijiao; Gu, Ping; Wei, Xunbin; Yang, Guo-Yuan; Gu, Hongchen; Zhang, Chunfu

2013-05-01

Multifunctional probes with high MRI sensitivity and high efficiency for cell labeling are desirable for MR cell imaging. Herein, we have fabricated fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (fmSiO4@SPIONs) for neural progenitor cell (C17.2) MR imaging. FmSiO4@SPIONs were discrete and uniform in size, and had a clear core-shell structure. The magnetic core size was about 10 nm and the fluorescent mesoporous silica coating layer was around 20 nm. Compared with fluorescent dense silica-coated SPIONs (fdSiO4@SPIONs) with a similar size, fmSiO4@SPIONs demonstrated higher MR sensitivity and cell labeling efficiency. When implanted into the right hemisphere of stroke mice, contralateral to the ischemic territory, a small amount of labeled cells were able to be tracked migrating to the lesion sites using a clinical MRI scanner (3 T). More impressively, even when administered intravenously, the labeled cells could also be monitored homing to the ischemic area. MRI observations were corroborated by histological studies of the brain tissues. Our study demonstrated that fmSiO4@SPIONs are highly effective for cell imaging and hold great promise for MRI cell tracking in future.Multifunctional probes with high MRI sensitivity and high efficiency for cell labeling are desirable for MR cell imaging. Herein, we have fabricated fluorescent mesoporous silica-coated superparamagnetic iron oxide nanoparticles (fmSiO4@SPIONs) for neural progenitor cell (C17.2) MR imaging. FmSiO4@SPIONs were discrete and uniform in size, and had a clear core-shell structure. The magnetic core size was about 10 nm and the fluorescent mesoporous silica coating layer was around 20 nm. Compared with fluorescent dense silica-coated SPIONs (fdSiO4@SPIONs) with a similar size, fmSiO4@SPIONs demonstrated higher MR sensitivity and cell labeling efficiency. When implanted into the right hemisphere of stroke mice, contralateral to the ischemic territory, a small amount of labeled cells were able to be tracked migrating to the lesion sites using a clinical MRI scanner (3 T). More impressively, even when administered intravenously, the labeled cells could also be monitored homing to the ischemic area. MRI observations were corroborated by histological studies of the brain tissues. Our study demonstrated that fmSiO4@SPIONs are highly effective for cell imaging and hold great promise for MRI cell tracking in future. Electronic supplementary information (ESI) available: Details of cell internalization of fmSiO4@SPIONs compared with SHU555A, immunofluorescence image of the immature phenotype of labeled C17.2. See DOI: 10.1039/c3nr00119a

Self-Assembled Superparamagnetic Iron Oxide Nanoclusters for Universal Cell Labeling and MRI

NASA Astrophysics Data System (ADS)

Chen, Shuzhen; Zhang, Jun; Jiang, Shengwei; Lin, Gan; Luo, Bing; Yao, Huan; Lin, Yuchun; He, Chengyong; Liu, Gang; Lin, Zhongning

2016-05-01

Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used in a variety of biomedical applications, especially as contrast agents for magnetic resonance imaging (MRI) and cell labeling. In this study, SPIO nanoparticles were stabilized with amphiphilic low molecular weight polyethylenimine (PEI) in an aqueous phase to form monodispersed nanocomposites with a controlled clustering structure. The iron-based nanoclusters with a size of 115.3 ± 40.23 nm showed excellent performance on cellular uptake and cell labeling in different types of cells, moreover, which could be tracked by MRI with high sensitivity. The SPIO nanoclusters presented negligible cytotoxicity in various types of cells as detected using MTS, LDH, and flow cytometry assays. Significantly, we found that ferritin protein played an essential role in protecting stress from SPIO nanoclusters. Taken together, the self-assembly of SPIO nanoclusters with good magnetic properties provides a safe and efficient method for universal cell labeling with noninvasive MRI monitoring capability.

Biological Characteristics of Fluorescent Superparamagnetic Iron Oxide Labeled Human Dental Pulp Stem Cells

PubMed Central

Li, Ming-wei; Bai, Yu; Guo, Hui-hui

2017-01-01

Tracking transplanted stem cells is necessary to clarify cellular properties and improve transplantation success. In this study, we investigate the effects of fluorescent superparamagnetic iron oxide particles (SPIO) (Molday ION Rhodamine-B™, MIRB) on biological properties of human dental pulp stem cells (hDPSCs) and monitor hDPSCs in vitro and in vivo using magnetic resonance imaging (MRI). Morphological analysis showed that intracellular MIRB particles were distributed in the cytoplasm surrounding the nuclei of hDPSCs. 12.5–100 μg/mL MIRB all resulted in 100% labeling efficiency. MTT showed that 12.5–50 μg/mL MIRB could promote cell proliferation and MIRB over 100 μg/mL exhibited toxic effect on hDPSCs. In vitro MRI showed that 1 × 106 cells labeled with various concentrations of MIRB (12.5–100 μg/mL) could be visualized. In vivo MRI showed that transplanted cells could be clearly visualized up to 60 days after transplantation. These results suggest that 12.5–50 μg/mL MIRB is a safe range for labeling hDPSCs. MIRB labeled hDPSCs cell can be visualized by MRI in vitro and in vivo. These data demonstrate that MIRB is a promising candidate for hDPSCs tracking in hDPSCs based dental pulp regeneration therapy. PMID:28298928

Imaging macrophage distribution and density in mammary tumors and lung metastases using fluorine-19 MRI cell tracking.

PubMed

Makela, Ashley V; Foster, Paula J

2018-09-01

The presence of tumor-associated macrophages (TAMs) correlates with breast cancer progression and metastatic spread. Metastasis-associated macrophages (MAMs) are also recruited to distant sites, where they support metastatic growth. In this study, we demonstrate that in vivo fluorine-19 ( 19 F)-based MRI cell tracking can evaluate the density and distribution of macrophages within murine breast cancer tumors and associated metastases. Three murine breast cancer cell lines with different metastatic potentials (4T1, 168FARN, and 67NR) were implanted into the mammary fat pad in mice. In vivo whole body 19 F MRI was performed on tumor-bearing mice 24 hours post-intravenous injection of a perfluorocarbon (PFC) agent, which was taken up by macrophages in situ. TAMs were detected mainly in the periphery of primary tumors, and higher numbers of TAMs were detected in the more aggressive 4T1 tumors. Tumors had significantly greater 19 F spins/mm 3 when they were smaller, suggesting more TAM infiltration in early-stage tumors. 19 F signal was observed within lung metastases in mice with 4T1 tumors, and fluorescence microscopy confirmed the presence of PFC-positive macrophages. This study shows for the first time proof of the ability to use MRI cell tracking to visualize MAMs in the lungs. The ability to detect and monitor the number of TAMs in individual tumors with 19 F MRI would allow for identification of breast tumors with heavy infiltration of TAMs and could be used as a biomarker for decisions about how to best treat these patients as well as for monitoring responses to therapy. Magn Reson Med 80:1138-1147, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

Imaging approaches for the study of cell based cardiac therapies

PubMed Central

Lau, Joe F.; Anderson, Stasia A.; Adler, Eric; Frank, Joseph A.

2009-01-01

Despite promising preclinical data, the treatment of cardiovascular diseases using embryonic, bone-marrow-derived, and skeletal myoblast stem cells has not yet come to fruition within mainstream clinical practice. Major obstacles in cardiac stem cell investigations include the ability to monitor cell engraftment and survival following implantation within the myocardium. Several cellular imaging modalities, including reporter gene and MRI-based tracking approaches, have emerged that provide the means to identify, localize and monitor stem cells longitudinally in vivo following implantation. This Review will examine the various cardiac cellular tracking modalities, including the combinatorial use of several probes in multimodality imaging, with a focus on data from the last five years. PMID:20027188

In vivo visualization and ex vivo quantification of murine breast cancer cells in the mouse brain using MRI cell tracking and electron paramagnetic resonance.

PubMed

Danhier, Pierre; Magat, Julie; Levêque, Philippe; De Preter, Géraldine; Porporato, Paolo E; Bouzin, Caroline; Jordan, Bénédicte F; Demeur, Gladys; Haufroid, Vincent; Feron, Olivier; Sonveaux, Pierre; Gallez, Bernard

2015-03-01

Cell tracking could be useful to elucidate fundamental processes of cancer biology such as metastasis. The aim of this study was to visualize, using MRI, and to quantify, using electron paramagnetic resonance (EPR), the entrapment of murine breast cancer cells labeled with superparamagnetic iron oxide particles (SPIOs) in the mouse brain after intracardiac injection. For this purpose, luciferase-expressing murine 4 T1-luc breast cancer cells were labeled with fluorescent Molday ION Rhodamine B SPIOs. Following intracardiac injection, SPIO-labeled 4 T1-luc cells were imaged using multiple gradient-echo sequences. Ex vivo iron oxide quantification in the mouse brain was performed using EPR (9 GHz). The long-term fate of 4 T1-luc cells after injection was characterized using bioluminescence imaging (BLI), brain MRI and immunofluorescence. We observed hypointense spots due to SPIO-labeled cells in the mouse brain 4 h after injection on T2 *-weighted images. Histology studies showed that SPIO-labeled cancer cells were localized within blood vessels shortly after delivery. Ex vivo quantification of SPIOs showed that less than 1% of the injected cells were taken up by the mouse brain after injection. MRI experiments did not reveal the development of macrometastases in the mouse brain several days after injection, but immunofluorescence studies demonstrated that these cells found in the brain established micrometastases. Concerning the metastatic patterns of 4 T1-luc cells, an EPR biodistribution study demonstrated that SPIO-labeled 4 T1-luc cells were also entrapped in the lungs of mice after intracardiac injection. BLI performed 6 days after injection of 4 T1-luc cells showed that this cell line formed macrometastases in the lungs and in the bones. Conclusively, EPR and MRI were found to be complementary for cell tracking applications. MRI cell tracking at 11.7 T allowed sensitive detection of isolated SPIO-labeled cells in the mouse brain, whereas EPR allowed the assessment of the number of SPIO-labeled cells in organs shortly after injection. Copyright © 2015 John Wiley & Sons, Ltd.

Mesenchymal Stem Cell Preparation and Transfection-free Ferumoxytol Labeling for MRI Cell Tracking.

PubMed

Liu, Li; Ho, Chien

2017-11-15

Mesenchymal stem cells (MSCs) are multipotent cells and are the most widely studied cell type for stem cell therapies. In vivo cell tracking of MSCs labeled with an FDA-approved superparamagnetic iron-oxide (SPIO) particle by magnetic resonance imaging (MRI) provides essential information, e.g., MSC engraftment, survival, and fate, thus improving cell therapy accuracy. However, current methodology for labeling MSCs with Ferumoxytol (Feraheme ® ), the only FDA-approved SPIO particle, needs transfection agents. This unit describes a new "bio-mimicry" protocol to prepare more native MSCs by using more "in vivo environment" of MSCs, so that the phagocytic activity of cultured MSCs is restored and expanded MSCs can be labeled with Ferumoxytol, without the need for transfection agents and/or electroporation. Moreover, MSCs re-size to a more native size, reducing from 32.0 to 19.5 μm. The MSCs prepared from this protocol retain more native properties and would be useful for biomedical applications and MSC-tracking studies by MRI. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Magnetic Resonance Imaging–Guided versus Surrogate-Based Motion Tracking in Liver Radiation Therapy: A Prospective Comparative Study

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

Paganelli, Chiara, E-mail: chiara.paganelli@polimi.it; Seregni, Matteo; Fattori, Giovanni

Purpose: This study applied automatic feature detection on cine–magnetic resonance imaging (MRI) liver images in order to provide a prospective comparison between MRI-guided and surrogate-based tracking methods for motion-compensated liver radiation therapy. Methods and Materials: In a population of 30 subjects (5 volunteers plus 25 patients), 2 oblique sagittal slices were acquired across the liver at high temporal resolution. An algorithm based on scale invariant feature transform (SIFT) was used to extract and track multiple features throughout the image sequence. The position of abdominal markers was also measured directly from the image series, and the internal motion of each featuremore » was quantified through multiparametric analysis. Surrogate-based tumor tracking with a state-of-the-art external/internal correlation model was simulated. The geometrical tracking error was measured, and its correlation with external motion parameters was also investigated. Finally, the potential gain in tracking accuracy relying on MRI guidance was quantified as a function of the maximum allowed tracking error. Results: An average of 45 features was extracted for each subject across the whole liver. The multi-parametric motion analysis reported relevant inter- and intrasubject variability, highlighting the value of patient-specific and spatially-distributed measurements. Surrogate-based tracking errors (relative to the motion amplitude) were were in the range 7% to 23% (1.02-3.57mm) and were significantly influenced by external motion parameters. The gain of MRI guidance compared to surrogate-based motion tracking was larger than 30% in 50% of the subjects when considering a 1.5-mm tracking error tolerance. Conclusions: Automatic feature detection applied to cine-MRI allows detailed liver motion description to be obtained. Such information was used to quantify the performance of surrogate-based tracking methods and to provide a prospective comparison with respect to MRI-guided radiation therapy, which could support the definition of patient-specific optimal treatment strategies.« less

Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes.

PubMed

Mahmoudi, Morteza; Tachibana, Atsushi; Goldstone, Andrew B; Woo, Y Joseph; Chakraborty, Papia; Lee, Kayla R; Foote, Chandler S; Piecewicz, Stephanie; Barrozo, Joyce C; Wakeel, Abdul; Rice, Bradley W; Bell Iii, Caleb B; Yang, Phillip C

2016-06-06

Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.

Fluorine-19 MRI Contrast Agents for Cell Tracking and Lung Imaging

PubMed Central

Fox, Matthew S.; Gaudet, Jeffrey M.; Foster, Paula J.

2015-01-01

Fluorine-19 (19F)-based contrast agents for magnetic resonance imaging stand to revolutionize imaging-based research and clinical trials in several fields of medical intervention. First, their use in characterizing in vivo cell behavior may help bring cellular therapy closer to clinical acceptance. Second, their use in lung imaging provides novel noninvasive interrogation of the ventilated airspaces without the need for complicated, hard-to-distribute hardware. This article reviews the current state of 19F-based cell tracking and lung imaging using magnetic resonance imaging and describes the link between the methods across these fields and how they may mutually benefit from solutions to mutual problems encountered when imaging 19F-containing compounds, as well as hardware and software advancements. PMID:27042089

Paramagnetic nanoparticles to track and quantify in vivo immune human therapeutic cells

NASA Astrophysics Data System (ADS)

Aspord, Caroline; Laurin, David; Janier, Marc F.; Mandon, Céline A.; Thivolet, Charles; Villiers, Christian; Mowat, Pierre; Madec, Anne-Marie; Tillement, Olivier; Perriat, Pascal; Louis, Cédric; Bérard, Frédéric; Marche, Patrice N.; Plumas, Joël; Billotey, Claire

2013-11-01

This study aims to investigate gadolinium-based nanoparticles (Gd-HNP) for in vitro labeling of human plasmacytoid dendritic cells (HuPDC) to allow for in vivo tracking and HuPDC quantifying using magnetic resonance imaging (MRI) following parenteral injection. Human plasmacytoid DC were labeled (LabHuPDC) with fluorescent Gd-HNP (Gd-FITC-HNP) and injected via intraperitoneal and intravenous routes in 4-5 NOD-SCID β2m-/-mice (treated mice = TM). Control mice (CM) were similarly injected with unlabeled HuPDC. In vivo 7 T MRI was performed 24 h later and all spleens were removed in order to measure Gd and fluorescence contents and identify HuPDC. Gd-FITC-HNP efficiently labeled HuPDC (0.05 to 0.1 pg per cell), without altering viability and activation properties. The magnetic resonance (MR) signal was exclusively due to HuPDC. The normalized MR splenic intensity for TM was significantly higher than for CM (p < 0.024), and highly correlated with the spleen Gd content (r = 0.97), and the number of HuPDC found in the spleen (r = 0.94). Gd-FITC-HNP allowed for in vivo tracking and HuPDC quantifying by means of MRI following parenteral injection, with very high sensitivity (<3000 cells per mm3). The safety of these new nanoparticle types must be confirmed via extensive toxicology tests including in vivo stability and biodistribution studies.This study aims to investigate gadolinium-based nanoparticles (Gd-HNP) for in vitro labeling of human plasmacytoid dendritic cells (HuPDC) to allow for in vivo tracking and HuPDC quantifying using magnetic resonance imaging (MRI) following parenteral injection. Human plasmacytoid DC were labeled (LabHuPDC) with fluorescent Gd-HNP (Gd-FITC-HNP) and injected via intraperitoneal and intravenous routes in 4-5 NOD-SCID β2m-/-mice (treated mice = TM). Control mice (CM) were similarly injected with unlabeled HuPDC. In vivo 7 T MRI was performed 24 h later and all spleens were removed in order to measure Gd and fluorescence contents and identify HuPDC. Gd-FITC-HNP efficiently labeled HuPDC (0.05 to 0.1 pg per cell), without altering viability and activation properties. The magnetic resonance (MR) signal was exclusively due to HuPDC. The normalized MR splenic intensity for TM was significantly higher than for CM (p < 0.024), and highly correlated with the spleen Gd content (r = 0.97), and the number of HuPDC found in the spleen (r = 0.94). Gd-FITC-HNP allowed for in vivo tracking and HuPDC quantifying by means of MRI following parenteral injection, with very high sensitivity (<3000 cells per mm3). The safety of these new nanoparticle types must be confirmed via extensive toxicology tests including in vivo stability and biodistribution studies. Corresponding address: Service de Médecine Nucléaire, Hôpital, Nord - CHU Saint-Etienne, Avenue Albert Raimond, 42270 Saint-Priest-en-Jarez, France. E-mail: claire.billotey@chu-st-etienne.fr

Use of Nanoparticle Contrast Agents for Cell Tracking with Computed Tomography

PubMed Central

2017-01-01

Efforts to develop novel cell-based therapies originated with the first bone marrow transplant on a leukemia patient in 1956. Preclinical and clinical examples of cell-based treatment strategies have shown promising results across many disciplines in medicine, with recent advances in immune cell therapies for cancer producing remarkable response rates, even in patients with multiple treatment failures. However, cell-based therapies suffer from inconsistent outcomes, motivating the search for tools that allow monitoring of cell delivery and behavior in vivo. Noninvasive cell imaging techniques, also known as cell tracking, have been developed to address this issue. These tools can allow real-time, quantitative, and long-term monitoring of transplanted cells in the recipient, providing insight on cell migration, distribution, viability, differentiation, and fate, all of which play crucial roles in treatment efficacy. Understanding these parameters allows the optimization of cell choice, delivery route, and dosage for therapy and advances cell-based therapy for specific clinical uses. To date, most cell tracking work has centered on imaging modalities such as MRI, radionuclide imaging, and optical imaging. However, X-ray computed tomography (CT) is an emerging method for cell tracking that has several strengths such as high spatial and temporal resolution, and excellent quantitative capabilities. The advantages of CT for cell tracking are enhanced by its wide availability and cost effectiveness, allowing CT to become one of the most popular clinical imaging modalities and a key asset in disease diagnosis. In this review, we will discuss recent advances in cell tracking methods using X-ray CT in various applications, in addition to predictions on how the field will progress. PMID:28485976

Tracking stem cell migration and survival in brain injury: current approaches and future prospects.

PubMed

Darkazalli, Ali; Levenson, Cathy W

2012-10-01

In recent years, stem cell-mediated therapies have gained considerable ground as potential treatments for a wide variety of brain pathologies including traumatic brain injury, stroke and neurodegenerative diseases. Despite extensive preclinical studies, many of these therapies have not been fully translated into viable clinical approaches. This is partly due to our inability to reliably track and monitor transplanted stem cells longitudinally over long periods of time in vivo. In this review, we discuss the predominant histological cell tracing methodologies, such as immunohistochemistry, and fluorescent cellular dyes and proteins, and compare them to emerging cellular imaging technologies. We show that advances in magnetic resonance imaging (MRI) have resulted in opportunities to use this technology to further our understanding of stem cell characteristics and behaviors in vivo. While MRI may not completely replace conventional cell tracking methods in pre-clinical, mechanistic work, it is clear that it has the potential to function as a powerful diagnostic tool for tracking stem cell migration and survival as well as for evaluating the efficacy of stem cell-mediated therapies.

Nanomaterials for miRNA delivery and non-invasive imaging in cardiovascular regeneration

NASA Astrophysics Data System (ADS)

Gomes, Renata Sofia Mota

The development of noninvasive platforms to assess cell fate after transplantation is of utmost importance in the context of Regenerative Medicine. Magnetic Resonance Imaging (MRI) is a powerful non-invasive imaging platform, heavily relying on the use of contrast agents, mostly nanoparticles (NPs). Gadolinium (Gd) and Superparamagnetic Iron Oxide (SPIO) NPs are contrast agents in clinical use, however these agents may cause liver toxicity, give rise to image artifacts in MRI, and typically have not been used as a drug delivery system. In this work, we developed a novel NP formulation containing fluorine to overcome the previous limitations. The NPs are based on poly(lactic-co-glycolic acid) (PLGA) which is a biocompatible and versatile polymer approved for human use . PLGA NPs containing fluorine were developed to label and track cells overtime and as vectors for microRNA (miR) delivery, which improves cell survival in hypoxic conditions. Herein we show that the fluorine-based NPs are a reliable approach to track non-invasively cells with clinical relevance (endothelial cells and cord-blood derived mononuclear cells) and simultaneously control the intracellular delivery of pro-survival and pro-angiogenic miRs. Also systems for in vitro and in vivo imaging via MRI of fluorine are developed and here explained. Furthermore in vivo studies are performed which show the therapeutic uses of such system. Additionally we also address the optimization of protocols for stem cell culture which may enhance proliferation and promote pluripotency in cardiac stem cells (CSCs) so as we can fully explore the potential of these cells in vivo using out novel theranostic NPs platform. We are the first authors developing and relating these novel developments.

Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering.

PubMed

Saldanha, Karl J; Doan, Ryan P; Ainslie, Kristy M; Desai, Tejal A; Majumdar, Sharmila

2011-01-01

To examine mesenchymal stem cell (MSC) labeling with micrometer-sized iron oxide particles (MPIOs) for magnetic resonance imaging (MRI)-based tracking and its application to monitoring articular cartilage regeneration. Rabbit MSCs were labeled using commercial MPIOs. In vitro MRI was performed with gradient echo (GRE) and spin echo (SE) sequences at 3T and quantitatively characterized using line profile and region of interest analysis. Ex vivo MRI of hydrogel-encapsulated labeled MSCs implanted within a bovine knee was performed with spoiled GRE (SPGR) and T(1ρ) sequences. Fluorescence microscopy, labeling efficiency, and chondrogenesis of MPIO-labeled cells were also examined. MPIO labeling results in efficient contrast uptake and signal loss that can be visualized and quantitatively characterized via MRI. SPGR imaging of implanted cells results in ex vivo detection within native tissue, and T(1ρ) imaging is unaffected by the presence of labeled cells immediately following implantation. MPIO labeling does not affect quantitative glycosaminoglycan production during chondrogenesis, but iron aggregation hinders extracellular matrix visualization. This aggregation may result from excess unincorporated particles following labeling and is an issue that necessitates further investigation. This study demonstrates the promise of MPIO labeling for monitoring cartilage regeneration and highlights its potential in the development of cell-based tissue engineering strategies. Published by Elsevier Inc.

Cellular Imaging With MRI.

PubMed

Makela, Ashley V; Murrell, Donna H; Parkins, Katie M; Kara, Jenna; Gaudet, Jeffrey M; Foster, Paula J

2016-10-01

Cellular magnetic resonance imaging (MRI) is an evolving field of imaging with strong translational and research potential. The ability to detect, track, and quantify cells in vivo and over time allows for studying cellular events related to disease processes and may be used as a biomarker for decisions about treatments and for monitoring responses to treatments. In this review, we discuss methods for labeling cells, various applications for cellular MRI, the existing limitations, strategies to address these shortcomings, and clinical cellular MRI.

Noninvasive in vivo tracking of mesenchymal stem cells and evaluation of cell therapeutic effects in a murine model using a clinical 3.0 T MRI.

PubMed

Drey, Florian; Choi, Yeong-Hoon; Neef, Klaus; Ewert, Birgit; Tenbrock, Arne; Treskes, Philipp; Bovenschulte, Henning; Liakopoulos, Oliver J; Brenkmann, Meike; Stamm, Christof; Wittwer, Thorsten; Wahlers, Thorsten

2013-01-01

Cardiac cell therapy with mesenchymal stem cells (MSCs) represents a promising treatment approach for end-stage heart failure. However, little is known about the underlying mechanisms and the fate of the transplanted cells. The objective of the presented work is to determine the feasibility of magnetic resonance imaging (MRI) and in vivo monitoring after transplantation into infarcted mouse hearts using a clinical 3.0 T MRI device. The labeling procedure of bone marrow-derived MSCs with micron-sized paramagnetic iron oxide particles (MPIOs) did not affect the viability of the cells and their cell type-defining properties when compared to unlabeled cells. Using a clinical 3.0 T MRI scanner equipped with a dedicated small animal solenoid coil, 10(5) labeled MSCs could be detected and localized in the mouse hearts for up to 4 weeks after intramyocardial transplantation. Weekly ECG-gated scans using T1-weighted sequences were performed, and left ventricular function was assessed. Histological analysis of hearts confirmed the survival of labeled MSCs in the target area up to 4 weeks after transplantation. In conclusion, in vivo tracking of labeled MSCs using a clinical 3.0 T MRI scanner is feasible. In combination with assessment of heart function, this technology allows the monitoring of the therapeutic efficacy of regenerative therapies in a small animal model.

Magnetic poly(lactide-co-glycolide) (PLGA) and cellulose particles for MRI-based cell tracking

PubMed Central

Nkansah, Michael K.; Thakral, Durga; Shapiro, Erik M.

2010-01-01

Biodegradable, superparamagnetic micro- and nanoparticles of poly(lactide-co-glycolide) (PLGA) and cellulose were designed, fabricated and characterized for magnetic cell labeling. Monodisperse nanocrystals of magnetite were incorporated into micro- and nanoparticles of PLGA and cellulose with high efficiency using an oil-in-water single emulsion technique. Superparamagnetic cores had high magnetization (72.1 emu/g). The resulting polymeric particles had smooth surface morphology and high magnetite content (43.3 wt% for PLGA and 69.6 wt% for cellulose). While PLGA and cellulose nanoparticles displayed highest r2* values per millimole of iron (399 s-1mM-1 for cellulose and 505 s-1mM-1 for PLGA), micron-sized PLGA particles had a much higher r2* per particle than either. After incubation for a month in citrate buffer (pH 5.5), magnetic PLGA particles lost close to 50% of their initial r2* molar relaxivity, while magnetic cellulose particles remained intact, preserving over 85% of their initial r2* molar relaxivity. Lastly, mesenchymal stem cells and human breast adenocarcinoma cells were magnetically labeled using these particles with no detectable cytotoxicity. These particles are ideally suited for non-invasive cell tracking in vivo via MRI and due to their vastly different degradation properties, offer unique potential for dedicated use for either short (PLGA-based particles) or long term (cellulose-based particles) experiments. PMID:21404328

A preclinical murine model for the early detection of radiation-induced brain injury using magnetic resonance imaging and behavioral tests for learning and memory: with applications for the evaluation of possible stem cell imaging agents and therapies.

PubMed

Ngen, Ethel J; Wang, Lee; Gandhi, Nishant; Kato, Yoshinori; Armour, Michael; Zhu, Wenlian; Wong, John; Gabrielson, Kathleen L; Artemov, Dmitri

2016-06-01

Stem cell therapies are being developed for radiotherapy-induced brain injuries (RIBI). Magnetic resonance imaging (MRI) offers advantages for imaging transplanted stem cells. However, most MRI cell-tracking techniques employ superparamagnetic iron oxide particles (SPIOs), which are difficult to distinguish from hemorrhage. In current preclinical RIBI models, hemorrhage occurs concurrently with other injury markers. This makes the evaluation of the recruitment of transplanted SPIO-labeled stem cells to injury sites difficult. Here, we developed a RIBI model, with early injury markers reflective of hippocampal dysfunction, which can be detected noninvasively with MRI and behavioral tests. Lesions were generated by sub-hemispheric irradiation of mouse hippocampi with single X-ray beams of 80 Gy. Lesion formation was monitored with anatomical and contrast-enhanced MRI and changes in memory and learning were assessed with fear-conditioning tests. Early injury markers were detected 2 weeks after irradiation. These included an increase in the permeability of the blood-brain barrier, demonstrated by a 92 ± 20 % contrast enhancement of the irradiated versus the non-irradiated brain hemispheres, within 15 min of the administration of an MRI contrast agent. A change in short-term memory was also detected, as demonstrated by a 40.88 ± 5.03 % decrease in the freezing time measured during the short-term memory context test at this time point, compared to that before irradiation. SPIO-labeled stem cells transplanted contralateral to the lesion migrated toward the lesion at this time point. No hemorrhage was detected up to 10 weeks after irradiation. This model can be used to evaluate SPIO-based stem cell-tracking agents, short-term.

Magneto-optical labeling of fetal neural stem cells for in vivo MRI tracking.

PubMed

Flexman, J A; Minoshima, S; Kim, Y; Cross, D J

2006-01-01

Neural stem cell therapy for neurological pathologies, such as Alzheimer's and Parkinson's disease, may delay the onset of symptoms, replace damaged neurons and/or support the survival of endogenous cells. Magnetic resonance imaging (MRI) can be used to track magnetically labeled cells in vivo to observe migration. Prior to transplantation, labeled cells must be characterized to show that they retain their intrinsic properties, such as cell proliferation into neurospheres in a supplemented environment. In vivo images must also be correlated to sensitive, histological markers. In this study, we show that fetus-derived neural stem cells can be co-labeled with superparamagnetic iron oxide and PKH26, a fluorescent dye. Labeled cells retain the ability to proliferate into neurospheres in culture, but labeling prevents neurospheres from merging in a non-adherent culture environment. After labeled NSCs were transplantation into the rat brain, their location and subsequent migration along the corpus callosum was detected using MRI. This study demonstrates an imaging paradigm with which to develop an in vivo assay for quantitatively evaluating fetal neural stem cell migration.

MRI-based dynamic tracking of an untethered ferromagnetic microcapsule navigating in liquid

NASA Astrophysics Data System (ADS)

Dahmen, Christian; Belharet, Karim; Folio, David; Ferreira, Antoine; Fatikow, Sergej

2016-04-01

The propulsion of ferromagnetic objects by means of MRI gradients is a promising approach to enable new forms of therapy. In this work, necessary techniques are presented to make this approach work. This includes path planning algorithms working on MRI data, ferromagnetic artifact imaging and a tracking algorithm which delivers position feedback for the ferromagnetic objects, and a propulsion sequence to enable interleaved magnetic propulsion and imaging. Using a dedicated software environment, integrating path-planning methods and real-time tracking, a clinical MRI system is adapted to provide this new functionality for controlled interventional targeted therapeutic applications. Through MRI-based sensing analysis, this article aims to propose a framework to plan a robust pathway to enhance the navigation ability to reach deep locations in the human body. The proposed approaches are validated with different experiments.

Voltage-based device tracking in a 1.5 Tesla MRI during imaging: initial validation in swine models.

PubMed

Schmidt, Ehud J; Tse, Zion T H; Reichlin, Tobias R; Michaud, Gregory F; Watkins, Ronald D; Butts-Pauly, Kim; Kwong, Raymond Y; Stevenson, William; Schweitzer, Jeffrey; Byrd, Israel; Dumoulin, Charles L

2014-03-01

Voltage-based device-tracking (VDT) systems are commonly used for tracking invasive devices in electrophysiological cardiac-arrhythmia therapy. During electrophysiological procedures, electro-anatomic mapping workstations provide guidance by integrating VDT location and intracardiac electrocardiogram information with X-ray, computerized tomography, ultrasound, and MR images. MR assists navigation, mapping, and radiofrequency ablation. Multimodality interventions require multiple patient transfers between an MRI and the X-ray/ultrasound electrophysiological suite, increasing the likelihood of patient-motion and image misregistration. An MRI-compatible VDT system may increase efficiency, as there is currently no single method to track devices both inside and outside the MRI scanner. An MRI-compatible VDT system was constructed by modifying a commercial system. Hardware was added to reduce MRI gradient-ramp and radiofrequency unblanking pulse interference. VDT patches and cables were modified to reduce heating. Five swine cardiac VDT electro-anatomic mapping interventions were performed, navigating inside and thereafter outside the MRI. Three-catheter VDT interventions were performed at >12 frames per second both inside and outside the MRI scanner with <3 mm error. Catheters were followed on VDT- and MRI-derived maps. Simultaneous VDT and imaging was possible in repetition time >32 ms sequences with <0.5 mm errors, and <5% MRI signal-to-noise ratio (SNR) loss. At shorter repetition times, only intracardiac electrocardiogram was reliable. Radiofrequency heating was <1.5°C. An MRI-compatible VDT system is feasible. Copyright © 2013 Wiley Periodicals, Inc.

Voltage-based Device Tracking in a 1.5 Tesla MRI during Imaging: Initial validation in swine models

PubMed Central

Schmidt, Ehud J; Tse, Zion TH; Reichlin, Tobias R; Michaud, Gregory F; Watkins, Ronald D; Butts-Pauly, Kim; Kwong, Raymond Y; Stevenson, William; Schweitzer, Jeffrey; Byrd, Israel; Dumoulin, Charles L

2013-01-01

Purpose Voltage-based device-tracking (VDT) systems are commonly used for tracking invasive devices in electrophysiological (EP) cardiac-arrhythmia therapy. During EP procedures, electro-anatomic-mapping (EAM) workstations provide guidance by integrating VDT location and intra-cardiac-ECG information with X-ray, CT, Ultrasound, and MR images. MR assists navigation, mapping and radio-frequency-ablation. Multi-modality interventions require multiple patient transfers between an MRI and the X-ray/ultrasound EP suite, increasing the likelihood of patient-motion and image mis-registration. An MRI-compatible VDT system may increase efficiency, since there is currently no single method to track devices both inside and outside the MRI scanner. Methods An MRI-compatible VDT system was constructed by modifying a commercial system. Hardware was added to reduce MRI gradient-ramp and radio-frequency-unblanking-pulse interference. VDT patches and cables were modified to reduce heating. Five swine cardiac VDT EAM-mapping interventions were performed, navigating inside and thereafter outside the MRI. Results Three-catheter VDT interventions were performed at >12 frames-per-second both inside and outside the MRI scanner with <3mm error. Catheters were followed on VDT- and MRI-derived maps. Simultaneous VDT and imaging was possible in repetition-time (TR) >32 msec sequences with <0.5mm errors, and <5% MRI SNR loss. At shorter TRs, only intra-cardiac-ECG was reliable. RF Heating was <1.5C°. Conclusion An MRI-compatible VDT system is feasible. PMID:23580479

Iron Oxide as an MRI Contrast Agent for Cell Tracking

PubMed Central

Korchinski, Daniel J.; Taha, May; Yang, Runze; Nathoo, Nabeela; Dunn, Jeff F.

2015-01-01

Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation. PMID:26483609

Advances in using MRI probes and sensors for in vivo cell tracking as applied to regenerative medicine

PubMed Central

Srivastava, Amit K.; Kadayakkara, Deepak K.; Bar-Shir, Amnon; Gilad, Assaf A.; McMahon, Michael T.; Bulte, Jeff W. M.

2015-01-01

The field of molecular and cellular imaging allows molecules and cells to be visualized in vivo non-invasively. It has uses not only as a research tool but in clinical settings as well, for example in monitoring cell-based regenerative therapies, in which cells are transplanted to replace degenerating or damaged tissues, or to restore a physiological function. The success of such cell-based therapies depends on several critical issues, including the route and accuracy of cell transplantation, the fate of cells after transplantation, and the interaction of engrafted cells with the host microenvironment. To assess these issues, it is necessary to monitor transplanted cells non-invasively in real-time. Magnetic resonance imaging (MRI) is a tool uniquely suited to this task, given its ability to image deep inside tissue with high temporal resolution and sensitivity. Extraordinary efforts have recently been made to improve cellular MRI as applied to regenerative medicine, by developing more advanced contrast agents for use as probes and sensors. These advances enable the non-invasive monitoring of cell fate and, more recently, that of the different cellular functions of living cells, such as their enzymatic activity and gene expression, as well as their time point of cell death. We present here a review of recent advancements in the development of these probes and sensors, and of their functioning, applications and limitations. PMID:26035841

Labeling and Magnetic Resonance Imaging of Exosomes Isolated from Adipose Stem Cells.

PubMed

Busato, Alice; Bonafede, Roberta; Bontempi, Pietro; Scambi, Ilaria; Schiaffino, Lorenzo; Benati, Donatella; Malatesta, Manuela; Sbarbati, Andrea; Marzola, Pasquina; Mariotti, Raffaella

2017-06-19

Adipose stem cells (ASC) represent a promising therapeutic approach for neurodegenerative diseases. Most biological effects of ASC are probably mediated by extracellular vesicles, such as exosomes, which influence the surrounding cells. Current development of exosome therapies requires efficient and noninvasive methods to localize, monitor, and track the exosomes. Among imaging methods used for this purpose, magnetic resonance imaging (MRI) has advantages: high spatial resolution, rapid in vivo acquisition, and radiation-free operation. To be detectable with MRI, exosomes must be labeled with MR contrast agents, such as ultra-small superparamagnetic iron oxide nanoparticles (USPIO). Here, we set up an innovative approach for exosome labeling that preserves their morphology and physiological characteristics. We show that by labeling ASC with USPIO before extraction of nanovesicles, the isolated exosomes retain nanoparticles and can be visualized by MRI. The current work aims at validating this novel USPIO-based exosome labeling method by monitoring the efficiency of the labeling with MRI both in ASC and in exosomes. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Cell tracking with caged xenon: using cryptophanes as MRI reporters upon cellular internalization.

PubMed

Klippel, Stefan; Döpfert, Jörg; Jayapaul, Jabadurai; Kunth, Martin; Rossella, Federica; Schnurr, Matthias; Witte, Christopher; Freund, Christian; Schröder, Leif

2014-01-07

Caged xenon has great potential in overcoming sensitivity limitations for solution-state NMR detection of dilute molecules. However, no application of such a system as a magnetic resonance imaging (MRI) contrast agent has yet been performed with live cells. We demonstrate MRI localization of cells labeled with caged xenon in a packed-bed bioreactor working under perfusion with hyperpolarized-xenon-saturated medium. Xenon hosts enable NMR/MRI experiments with switchable contrast and selectivity for cell-associated versus unbound cages. We present MR images with 10(3) -fold sensitivity enhancement for cell-internalized, dual-mode (fluorescence/MRI) xenon hosts at low micromolar concentrations. Our results illustrate the capability of functionalized xenon to act as a highly sensitive cell tracer for MRI detection even without signal averaging. The method will bridge the challenging gap for translation to in vivo studies for the optimization of targeted biosensors and their multiplexing applications. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents.

PubMed

Patel, Daksha; Kell, Arnold; Simard, Benoit; Xiang, Bo; Lin, Hung Yu; Tian, Ganghong

2011-02-01

A new class of nanoparticle-based dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) contrast agents has been developed. The probe consists of a superparamagnetic iron oxide (SPIO) or manganese oxide core coated with 3,4-dihydroxy-D,L-phenylalanine (DL-DOPA). The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to DOPA termini. The DOTA modified nanoparticles allow chelation of copper for PET imaging. These surface functionalized nanoparticle-based probes have been characterized by various analytical techniques. The cell-labeling efficacy, cytotoxicity and relaxivity of these nanoparticles have been evaluated and compared with the same properties of one of the most commonly utilized MRI contrast agents, Feridex(®). Evidently, this new nanoparticle has a great potential for use in cell tracking with MRI and PET in the absence of transfecting agent. It is noteworthy that there is a sharp increase in r(2) relaxivity of these nanoparticles on coordination with Cu(2+) ions. Thus these iron oxide nanoparticles can also be explored as the smart magnetic resonance (MR) sensor for the detection of micromolar changes in copper concentration for neurodegenerative diseases such as Alzheimer's disease, Menkes and Wilson's diseases, amyotrophic lateral sclerosis and prion diseases. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Navigators for motion detection during real-time MRI-guided radiotherapy

NASA Astrophysics Data System (ADS)

Stam, Mette K.; Crijns, Sjoerd P. M.; Zonnenberg, Bernard A.; Barendrecht, Maurits M.; van Vulpen, Marco; Lagendijk, Jan J. W.; Raaymakers, Bas W.

2012-11-01

An MRI-linac system provides direct MRI feedback and with that the possibility of adapting radiation treatments to the actual tumour position. This paper addresses the use of fast 1D MRI, pencil-beam navigators, for this feedback. The accuracy of using navigators was determined on a moving phantom. The possibility of organ tracking and breath-hold monitoring based on navigator guidance was shown for the kidney. Navigators are accurate within 0.5 mm and the analysis has a minimal time lag smaller than 30 ms as shown for the phantom measurements. The correlation of 2D kidney images and navigators shows the possibility of complete organ tracking. Furthermore the breath-hold monitoring of the kidney is accurate within 1.5 mm, allowing gated radiotherapy based on navigator feedback. Navigators are a fast and precise method for monitoring and real-time tracking of anatomical landmarks. As such, they provide direct MRI feedback on anatomical changes for more precise radiation delivery.

Coregistration of Magnetic Resonance and Single Photon Emission Computed Tomography Images for Noninvasive Localization of Stem Cells Grafted in the Infarcted Rat Myocardium

PubMed Central

Shen, Dinggang; Liu, Dengfeng; Cao, Zixiong; Acton, Paul D.; Zhou, Rong

2008-01-01

This paper demonstrates the application of mutual information based coregistration of radionuclide and magnetic resonance imaging (MRI) in an effort to use multimodality imaging for noninvasive localization of stem cells grafted in the infarcted myocardium in rats. Radionuclide imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) inherently has high sensitivity and is suitable for tracking of labeled stem cells, while high-resolution MRI is able to provide detailed anatomical and functional information of myocardium. Thus, coregistration of PET or SPECT images with MRI will map the location and distribution of stem cells on detailed myocardium structures. To validate this coregistration method, SPECT data were simulated by using a Monte Carlo-based projector that modeled the pinhole-imaging physics assuming nonzero diameter and photon penetration at the edge. Translational and rotational errors of the coregistration were examined with respect to various SPECT activities, and they are on average about 0.50 mm and 0.82°, respectively. Only the rotational error is dependent on activity of SPECT data. Stem cells were labeled with 111 Indium oxyquinoline and grafted in the ischemic myocardium of a rat model. Dual-tracer small-animal SPECT images were acquired, which allowed simultaneous detection of 111In-labeled stem cells and of [99mTc]sestamibi to assess myocardial perfusion deficit. The same animals were subjected to cardiac MRI. A mutual-information-based coregistration method was then applied to the SPECT and MRIs. By coregistration, the 111 In signal from labeled cells was mapped into the akinetic region identified on cine MRIs; the regional perfusion deficit on the SPECT images also coincided with the akinetic region on the MR image. PMID:17053860

Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.

PubMed

Riegler, Johannes; Ebert, Antje; Qin, Xulei; Shen, Qi; Wang, Mouer; Ameen, Mohamed; Kodo, Kazuki; Ong, Sang-Ging; Lee, Won Hee; Lee, Grace; Neofytou, Evgenios; Gold, Joseph D; Connolly, Andrew J; Wu, Joseph C

2016-02-09

The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-09-15

Stem cells hold great promise for treating various diseases. However, one of the main drawbacks of stem cell therapy is the lack of non-invasive image-tracking technologies. Although magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging have been employed to analyse cellular and subcellular events via the assistance of contrast agents, the sensitivity and temporal resolution of MRI and the spatial resolution of NIRF are still shortcomings. In this study, superparamagnetic iron oxide nanocrystals and IR-780 dyes were co-encapsulated in stearic acid-modified polyethylenimine to form a dual-modality contrast agent with nano-size and positive charge. These resulting agents efficiently labelled stem cells and did not influence the cellular viability and differentiation. Moreover, the labelled cells showed the advantages of dual-modality imaging in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of dual 19 F and iron cellular MRI agents to track the infiltration of immune cells to the site of a rejected stem cell transplant.

PubMed

Gaudet, Jeffrey M; Hamilton, Amanda M; Chen, Yuanxin; Fox, Matthew S; Foster, Paula J

2017-08-01

Cellular MRI) was used to detect implanted human mesenchymal stem cells (hMSCs) and the resulting macrophage infiltration that occurs in response to xenotransplantation. Human mesenchymal stem cells were prelabeled with a fluorine-19 ( 19 F) agent prior to implantation, allowing for their visualization and quantification over time. Following implantation of 1 × 10 6 19 F-labeled hMSCs into the mouse hind limb, longitudinal imaging was performed to monitor the stem cell graft. Macrophages were labeled in situ by the intravenous administration of an ultrasmall superparamagentic iron oxide (USPIO), allowing for tracking of the inflammatory response. Quantification of 19 F MRI on day 0 agreed with the implanted number of cells, and 19 F signal decreased over time. By day 14, only 22% ± 11% of the original 19 F signal remained. In a second group, USPIO were administered intravenously after implantation of 19 F-labeled hMSCs. When imaged on day 2, a significant decrease in 19 F signal was observed compared to the first group alongside a large signal void region in the corresponding proton images. Immunohistochemistry confirmed the presence of iron-labeled macrophages in the stem cell tract. A dual-labeling technique was used to noninvasively track two distinct cell populations simultaneously. This information could be used to provide additional insight into the cause of graft failure. Magn Reson Med 78:713-720, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Fluorine (19F) MRS and MRI in biomedicine

PubMed Central

Ruiz-Cabello, Jesús; Barnett, Brad P.; Bottomley, Paul A.; Bulte, Jeff W.M.

2011-01-01

Shortly after the introduction of 1H MRI, fluorinated molecules were tested as MR-detectable tracers or contrast agents. Many fluorinated compounds, which are nontoxic and chemically inert, are now being used in a broad range of biomedical applications, including anesthetics, chemotherapeutic agents, and molecules with high oxygen solubility for respiration and blood substitution. These compounds can be monitored by fluorine (19F) MRI and/or MRS, providing a noninvasive means to interrogate associated functions in biological systems. As a result of the lack of endogenous fluorine in living organisms, 19F MRI of ‘hotspots’ of targeted fluorinated contrast agents has recently opened up new research avenues in molecular and cellular imaging. This includes the specific targeting and imaging of cellular surface epitopes, as well as MRI cell tracking of endogenous macrophages, injected immune cells and stem cell transplants. PMID:20842758

Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

PubMed

Emmert, Maximilian Y; Weber, Benedikt; Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P

2013-01-01

Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5)-5×10(5) human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy.

Intramyocardial Transplantation and Tracking of Human Mesenchymal Stem Cells in a Novel Intra-Uterine Pre-Immune Fetal Sheep Myocardial Infarction Model: A Proof of Concept Study

PubMed Central

Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M.; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E.; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P.

2013-01-01

Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70–75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7–9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×105–5×105 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow-Cytometry detected the cells within spleen, lungs, kidneys, thymus, bone-marrow and intra-peritoneal lavage, but not within the heart. For the first time we demonstrate the feasibility of intra-uterine, intra-myocardial stem-cell transplantation into the pre-immune fetal-sheep after MI. Utilizing cell-tracking strategies comprising advanced imaging-technologies and in-vitro tracking-tools, this novel model may serve as a unique platform to assess human cell-fate after intra-myocardial transplantation without the necessity of immunosuppressive-therapy. PMID:23533575

Towards the development of a spring-based continuum robot for neurosurgery

NASA Astrophysics Data System (ADS)

Kim, Yeongjin; Cheng, Shing Shin; Desai, Jaydev P.

2015-03-01

Brain tumor is usually life threatening due to the uncontrolled growth of abnormal cells native to the brain or the spread of tumor cells from outside the central nervous system to the brain. The risks involved in carrying out surgery within such a complex organ can cause severe anxiety in cancer patients. However, neurosurgery, which remains one of the more effective ways of treating brain tumors focused in a confined volume, can have a tremendously increased success rate if the appropriate imaging modality is used for complete tumor removal. Magnetic resonance imaging (MRI) provides excellent soft-tissue contrast and is the imaging modality of choice for brain tumor imaging. MRI combined with continuum soft robotics has immense potential to be the revolutionary treatment technique in the field of brain cancer. It eliminates the concern of hand tremor and guarantees a more precise procedure. One of the prototypes of Minimally Invasive Neurosurgical Intracranial Robot (MINIR-II), which can be classified as a continuum soft robot, consists of a snake-like body made of three segments of rapid prototyped plastic springs. It provides improved dexterity with higher degrees of freedom and independent joint control. It is MRI-compatible, allowing surgeons to track and determine the real-time location of the robot relative to the brain tumor target. The robot was manufactured in a single piece using rapid prototyping technology at a low cost, allowing it to disposable after each use. MINIR-II has two DOFs at each segment with both joints controlled by two pairs of MRI-compatible SMA spring actuators. Preliminary motion tests have been carried out using vision-tracking method and the robot was able to move to different positions based on user commands.

Motion prediction in MRI-guided radiotherapy based on interleaved orthogonal cine-MRI

NASA Astrophysics Data System (ADS)

Seregni, M.; Paganelli, C.; Lee, D.; Greer, P. B.; Baroni, G.; Keall, P. J.; Riboldi, M.

2016-01-01

In-room cine-MRI guidance can provide non-invasive target localization during radiotherapy treatment. However, in order to cope with finite imaging frequency and system latencies between target localization and dose delivery, tumour motion prediction is required. This work proposes a framework for motion prediction dedicated to cine-MRI guidance, aiming at quantifying the geometric uncertainties introduced by this process for both tumour tracking and beam gating. The tumour position, identified through scale invariant features detected in cine-MRI slices, is estimated at high-frequency (25 Hz) using three independent predictors, one for each anatomical coordinate. Linear extrapolation, auto-regressive and support vector machine algorithms are compared against systems that use no prediction or surrogate-based motion estimation. Geometric uncertainties are reported as a function of image acquisition period and system latency. Average results show that the tracking error RMS can be decreased down to a [0.2; 1.2] mm range, for acquisition periods between 250 and 750 ms and system latencies between 50 and 300 ms. Except for the linear extrapolator, tracking and gating prediction errors were, on average, lower than those measured for surrogate-based motion estimation. This finding suggests that cine-MRI guidance, combined with appropriate prediction algorithms, could relevantly decrease geometric uncertainties in motion compensated treatments.

Documenting the location of systematic transrectal ultrasound-guided prostate biopsies: correlation with multi-parametric MRI.

PubMed

Turkbey, Baris; Xu, Sheng; Kruecker, Jochen; Locklin, Julia; Pang, Yuxi; Shah, Vijay; Bernardo, Marcelino; Baccala, Angelo; Rastinehad, Ardeshir; Benjamin, Compton; Merino, Maria J; Wood, Bradford J; Choyke, Peter L; Pinto, Peter A

2011-03-29

During transrectal ultrasound (TRUS)-guided prostate biopsies, the actual location of the biopsy site is rarely documented. Here, we demonstrate the capability of TRUS-magnetic resonance imaging (MRI) image fusion to document the biopsy site and correlate biopsy results with multi-parametric MRI findings. Fifty consecutive patients (median age 61 years) with a median prostate-specific antigen (PSA) level of 5.8 ng/ml underwent 12-core TRUS-guided biopsy of the prostate. Pre-procedural T2-weighted magnetic resonance images were fused to TRUS. A disposable needle guide with miniature tracking sensors was attached to the TRUS probe to enable fusion with MRI. Real-time TRUS images during biopsy and the corresponding tracking information were recorded. Each biopsy site was superimposed onto the MRI. Each biopsy site was classified as positive or negative for cancer based on the results of each MRI sequence. Sensitivity, specificity, and receiver operating curve (ROC) area under the curve (AUC) values were calculated for multi-parametric MRI. Gleason scores for each multi-parametric MRI pattern were also evaluated. Six hundred and 5 systemic biopsy cores were analyzed in 50 patients, of whom 20 patients had 56 positive cores. MRI identified 34 of 56 positive cores. Overall, sensitivity, specificity, and ROC area values for multi-parametric MRI were 0.607, 0.727, 0.667, respectively. TRUS-MRI fusion after biopsy can be used to document the location of each biopsy site, which can then be correlated with MRI findings. Based on correlation with tracked biopsies, T2-weighted MRI and apparent diffusion coefficient maps derived from diffusion-weighted MRI are the most sensitive sequences, whereas the addition of delayed contrast enhancement MRI and three-dimensional magnetic resonance spectroscopy demonstrated higher specificity consistent with results obtained using radical prostatectomy specimens.

Nanoparticles and clinically applicable cell tracking

PubMed Central

Guenoun, Jamal; van Tiel, Sandra T; Krestin, Gabriel P

2015-01-01

In vivo cell tracking has emerged as a much sought after tool for design and monitoring of cell-based treatment strategies. Various techniques are available for pre-clinical animal studies, from which much has been learned and still can be learned. However, there is also a need for clinically translatable techniques. Central to in vivo cell imaging is labelling of cells with agents that can give rise to signals in vivo, that can be detected and measured non-invasively. The current imaging technology of choice for clinical translation is MRI in combination with labelling of cells with magnetic agents. The main challenge encountered during the cell labelling procedure is to efficiently incorporate the label into the cell, such that the labelled cells can be imaged at high sensitivity for prolonged periods of time, without the labelling process affecting the functionality of the cells. In this respect, nanoparticles offer attractive features since their structure and chemical properties can be modified to facilitate cellular incorporation and because they can carry a high payload of the relevant label into cells. While these technologies have already been applied in clinical trials and have increased the understanding of cell-based therapy mechanism, many challenges are still faced. PMID:26248872

Development of Multifunctional Magnetic Nanoparticles for Genetic Engineering and Tracking of Neural Stem Cells.

PubMed

Adams, Christopher; Israel, Liron Limor; Ostrovsky, Stella; Taylor, Arthur; Poptani, Harish; Lellouche, Jean-Paul; Chari, Divya

2016-04-06

Genetic modification of cell transplant populations and cell tracking ability are key underpinnings for effective cell therapies. Current strategies to achieve these goals utilize methods which are unsuitable for clinical translation because of related safety issues, and multiple protocol steps adding to cost and complexity. Multifunctional magnetic nanoparticles (MNPs) offering dual mode gene delivery and imaging contrast capacity offer a valuable tool in this context. Despite their key benefits, there is a critical lack of neurocompatible and multifunctional particles described for use with transplant populations for neurological applications. Here, a systematic screen of MNPs (using a core shown to cause contrast in magnetic resonance imaging (MRI)) bearing various surface chemistries (polyethylenimine (PEI) and oxidized PEI and hybrids of oxidized PEI/alginic acid, PEI/chitosan and PEI/polyamidoamine) is performed to test their ability to genetically engineer neural stem cells (NSCs; a cell population of high clinical relevance for central nervous system disorders). It is demonstrated that gene delivery to NSCs can be safely achieved using two of the developed formulations (PEI and oxPEI/alginic acid) when used in conjunction with oscillating magnetofection technology. After transfection, intracellular particles can be detected by histological procedures with labeled cells displaying contrast in MRI (for real time cell tracking). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fluorine (19F) MRS and MRI in biomedicine.

PubMed

Ruiz-Cabello, Jesús; Barnett, Brad P; Bottomley, Paul A; Bulte, Jeff W M

2011-02-01

Shortly after the introduction of (1)H MRI, fluorinated molecules were tested as MR-detectable tracers or contrast agents. Many fluorinated compounds, which are nontoxic and chemically inert, are now being used in a broad range of biomedical applications, including anesthetics, chemotherapeutic agents, and molecules with high oxygen solubility for respiration and blood substitution. These compounds can be monitored by fluorine ((19)F) MRI and/or MRS, providing a noninvasive means to interrogate associated functions in biological systems. As a result of the lack of endogenous fluorine in living organisms, (19)F MRI of 'hotspots' of targeted fluorinated contrast agents has recently opened up new research avenues in molecular and cellular imaging. This includes the specific targeting and imaging of cellular surface epitopes, as well as MRI cell tracking of endogenous macrophages, injected immune cells and stem cell transplants. Copyright © 2010 John Wiley & Sons, Ltd.

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

PubMed

Bernal, Giovanna M; LaRiviere, Michael J; Mansour, Nassir; Pytel, Peter; Cahill, Kirk E; Voce, David J; Kang, Shijun; Spretz, Ruben; Welp, Ulrich; Noriega, Sandra E; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2014-01-01

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles. © 2014.

Imaging free zinc levels in vivo - what can be learned?

PubMed

De Leon-Rodriguez, Luis; Lubag, Angelo Josue M; Sherry, A Dean

2012-12-01

Our ever-expanding knowledge about the role of zinc in biology includes its role in redox modulation, immune response, neurotransmission, reproduction, diabetes, cancer, and Alzheimers disease is galvanizing interest in detecting and monitoring the various forms of Zn(II) in biological systems. This paper reviews reported strategies for detecting and tracking of labile or "free" unchelated Zn(II) in tissues. While different bound structural forms of Zn(II) have been identified and studied in vitro by multiple techniques, very few molecular imaging methods have successfully tracked the ion in vivo. A number of MRI and optical strategies have now been reported for detection of free Zn(II) in cells and tissues but only a few have been applied successfully in vivo. A recent report of a MRI sensor for in vivo tracking of Zn(II) released from pancreatic β-cells during insulin secretion exemplifies the promise of rational design of new Zn(II) sensors for tracking this biologically important ion in vivo. Such studies promise to provide new insights into zinc trafficking in vivo and the critical role of this ion in many human diseases.

Evaluation of an image-based tracking workflow with Kalman filtering for automatic image plane alignment in interventional MRI.

PubMed

Neumann, M; Cuvillon, L; Breton, E; de Matheli, M

2013-01-01

Recently, a workflow for magnetic resonance (MR) image plane alignment based on tracking in real-time MR images was introduced. The workflow is based on a tracking device composed of 2 resonant micro-coils and a passive marker, and allows for tracking of the passive marker in clinical real-time images and automatic (re-)initialization using the microcoils. As the Kalman filter has proven its benefit as an estimator and predictor, it is well suited for use in tracking applications. In this paper, a Kalman filter is integrated in the previously developed workflow in order to predict position and orientation of the tracking device. Measurement noise covariances of the Kalman filter are dynamically changed in order to take into account that, according to the image plane orientation, only a subset of the 3D pose components is available. The improved tracking performance of the Kalman extended workflow could be quantified in simulation results. Also, a first experiment in the MRI scanner was performed but without quantitative results yet.

Magnetic resonance cell-tracking studies: spectrophotometry-based method for the quantification of cellular iron content after loading with superparamagnetic iron oxide nanoparticles.

PubMed

Böhm, Ingrid

2011-08-01

The purpose of this article is to present a user-friendly tool for quantifying the iron content of superparamagnetic labeled cells before cell tracking by magnetic resonance imaging (MRI). Iron quantification was evaluated by using Prussian blue staining and spectrophotometry. White blood cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Labeling was confirmed by light microscopy. Subsequently, the cells were embedded in a phantom and scanned on a 3 T magnetic resonance tomography (MRT) whole-body system. Mean peak wavelengths λ(peak) was determined at A(720 nm) (range 719-722 nm). Linearity was proven for the measuring range 0.5 to 10 μg Fe/mL (r  =  .9958; p  =  2.2 × 10(-12)). The limit of detection was 0.01 μg Fe/mL (0.1785 mM), and the limit of quantification was 0.04 μg Fe/mL (0.714 mM). Accuracy was demonstrated by comparison with atomic absorption spectrometry. Precision and robustness were also proven. On T(2)-weighted images, signal intensity varied according to the iron concentration of SPIO-labeled cells. Absorption spectrophotometry is both a highly sensitive and user-friendly technique that is feasible for quantifying the iron content of magnetically labeled cells. The presented data suggest that spectrophotometry is a promising tool for promoting the implementation of magnetic resonance-based cell tracking in routine clinical applications (from bench to bedside).

TU-PIS-Exhibit Hall-5: Use of the Enterprise-wide Dose Tracking Software Radimetrics In an Academic Medical System

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

Goode, A.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

TU-PIS-Exhibit Hall-3: Simultaneous tracking of patient and real time staff dose to optimize interventional workflow

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

Boon, S.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

Single slice US-MRI registration for neurosurgical MRI-guided US

NASA Astrophysics Data System (ADS)

Pardasani, Utsav; Baxter, John S. H.; Peters, Terry M.; Khan, Ali R.

2016-03-01

Image-based ultrasound to magnetic resonance image (US-MRI) registration can be an invaluable tool in image-guided neuronavigation systems. State-of-the-art commercial and research systems utilize image-based registration to assist in functions such as brain-shift correction, image fusion, and probe calibration. Since traditional US-MRI registration techniques use reconstructed US volumes or a series of tracked US slices, the functionality of this approach can be compromised by the limitations of optical or magnetic tracking systems in the neurosurgical operating room. These drawbacks include ergonomic issues, line-of-sight/magnetic interference, and maintenance of the sterile field. For those seeking a US vendor-agnostic system, these issues are compounded with the challenge of instrumenting the probe without permanent modification and calibrating the probe face to the tracking tool. To address these challenges, this paper explores the feasibility of a real-time US-MRI volume registration in a small virtual craniotomy site using a single slice. We employ the Linear Correlation of Linear Combination (LC2) similarity metric in its patch-based form on data from MNI's Brain Images for Tumour Evaluation (BITE) dataset as a PyCUDA enabled Python module in Slicer. By retaining the original orientation information, we are able to improve on the poses using this approach. To further assist the challenge of US-MRI registration, we also present the BOXLC2 metric which demonstrates a speed improvement to LC2, while retaining a similar accuracy in this context.

SU-E-J-240: Development of a Novel 4D MRI Sequence for Real-Time Liver Tumor Tracking During Radiotherapy

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

Zhuang, L; Burmeister, J; Ye, Y

2015-06-15

Purpose: To develop a Novel 4D MRI Technique that is feasible for realtime liver tumor tracking during radiotherapy. Methods: A volunteer underwent an abdominal 2D fast EPI coronal scan on a 3.0T MRI scanner (Siemens Inc., Germany). An optimal set of parameters was determined based on image quality and scan time. A total of 23 slices were scanned to cover the whole liver in the test scan. For each scan position, the 2D images were retrospectively sorted into multiple phases based on breathing signal extracted from the images. Consequently the 2D slices with same phase numbers were stacked to formmore » one 3D image. Multiple phases of 3D images formed the 4D MRI sequence representing one breathing cycle. Results: The optimal set of scan parameters were: TR= 57ms, TE= 19ms, FOV read= 320mm and flip angle= 30°, which resulted in a total scan time of 14s for 200 frames (FMs) per slice and image resolution of (2.5mm,2.5mm,5.0mm) in three directions. Ten phases of 3D images were generated, each of which had 23 slices. Based on our test scan, only 100FMs were necessary for the phase sorting process which may lower the scan time to 7s/100FMs/slice. For example, only 5 slices/35s are necessary for a 4D MRI scan to cover liver tumor size ≤ 2cm leading to the possibility of tumor trajectory tracking every 35s during treatment. Conclusion: The novel 4D MRI technique we developed can reconstruct a 4D liver MRI sequence representing one breathing cycle (7s/ slice) without an external monitor. This technique can potentially be used for real-time liver tumor tracking during radiotherapy.« less

Magnetic Resonance Imaging of Ferumoxytol-Labeled Human Mesenchymal Stem Cells in the Mouse Brain.

PubMed

Lee, Na Kyung; Kim, Hyeong Seop; Yoo, Dongkyeom; Hwang, Jung Won; Choi, Soo Jin; Oh, Wonil; Chang, Jong Wook; Na, Duk L

2017-02-01

The success of stem cell therapy is highly dependent on accurate delivery of stem cells to the target site of interest. Possible ways to track the distribution of MSCs in vivo include the use of reporter genes or nanoparticles. The U.S. Food and Drug Administration (FDA) has approved ferumoxytol (Feraheme® [USA], Rienso® [UK]) as a treatment for iron deficiency anemia. Ferumoxytol is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) that has recently been used to track the fate of transplanted cells using magnetic resonance imaging (MRI). The major objectives of this study were to demonstrate the feasibility of labeling hUCB-MSCs with ferumoxytol and to observe, through MRI, the engraftment of ferumoxytol-labeled human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) delivered via stereotactic injection into the hippocampi of a transgenic mouse model of familial Alzheimer's disease (5XFAD). Ferumoxytol had no toxic effects on the viability or stemness of hUCB-MSCs when assessed in vitro. Through MRI, hypointense signals were discernible at the site where ferumoxytol-labeled human MSCs were injected. Iron-positive areas were also observed in the engrafted hippocampi. The results from this study support the use of nanoparticle labeling to monitor transplanted MSCs in real time as a follow-up for AD stem cell therapy in the clinical field.

Whole body tracking of superparamagnetic iron oxide nanoparticle-labelled cells – a rheumatoid arthritis mouse model

PubMed Central

2013-01-01

Introduction The application of mesenchymal stem cells (MSCs) in treating rheumatoid arthritis (RA) has been made possible by the immunosuppressive and differentiation abilities of these cells. A non-invasive means of assessing cell integration and bio-distribution is fundamental in evaluating the risks and success of this therapy, thereby enabling clinical translation. This paper defines the use of superparamagnetic iron oxide nanoparticles (SPIONs) in conjunction with magnetic resonance imaging (MRI) to image and track MSCs in vivo within a murine model of RA. Methods Murine MSCs (mMSCs) were isolated, expanded and labelled with SiMAG, a commercially available particle. In vitro MRI visibility thresholds were investigated by labelling mMSCs with SiMAG with concentrations ranging from 0 to 10 μg/ml and resuspending varying cell doses (103 to 5 × 105 cells) in 2 mg/ml collagen prior to MR-imaging. Similarly, in vivo detection thresholds were identified by implanting 3 × 105 mMSCs labelled with 0 to 10 μg/ml SiMAG within the synovial cavity of a mouse and MR-imaging. Upon RA induction, 300,000 mMSCs labelled with SiMAG (10 μg/ml) were implanted via intra-articular injection and joint swelling monitored as an indication of RA development over seven days. Furthermore, the effect of SiMAG on cell viability, proliferation and differentiation was investigated. Results A minimum particle concentration of 1 μg/ml (300,000 cells) and cell dose of 100,000 cells (5 and 10 μg/ml) were identified as the in vitro MRI detection threshold. Cell viability, proliferation and differentiation capabilities were not affected, with labelled populations undergoing successful differentiation down osteogenic and adipogenic lineages. A significant decrease (P < 0.01) in joint swelling was measured in groups containing SiMAG-labelled and unlabelled mMSCs implying that the presence of SPIONs does not affect the immunomodulating properties of the cells. In vivo MRI scans demonstrated good contrast and the identification of SiMAG-labelled populations within the synovial joint up to 7 days post implantation. This was further confirmed using histological analysis. Conclusions We have been able to monitor and track the migration of stem cell populations within the rheumatic joint in a non-invasive manner. This manuscript goes further to highlight the key characteristics (biocompatible and the ability to create significant contrast at realistic doses within a clinical relevant system) demonstrated by SiMAG that should be incorporated into the design of a new clinically approved tracking agent. PMID:24406201

Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium.

PubMed

Blocki, Anna; Beyer, Sebastian; Dewavrin, Jean-Yves; Goralczyk, Anna; Wang, Yingting; Peh, Priscilla; Ng, Michael; Moonshi, Shehzahdi S; Vuddagiri, Susmitha; Raghunath, Michael; Martinez, Eliana C; Bhakoo, Kishore K

2015-06-01

The limited efficacy of cardiac cell-based therapy is thought to be due to poor cell retention within the myocardium. Hence, there is an urgent need for biomaterials that aid in long-term cell retention. This study describes the development of injectable microcapsules for the delivery of mesenchymal stem cells (MSCs) into the infarcted cardiac wall. These microcapsules comprise of low concentrations of agarose supplemented with extracellular matrix (ECM) proteins collagen and fibrin. Dextran sulfate, a negatively charged polycarbohydrate, was added to mimic glycosaminoglycans in the ECM. Cell viability assays showed that a combination of all components is necessary to support long-term survival and proliferation of MSCs within microcapsules. Following intramyocardial transplantation, microcapsules degraded slowly in vivo and did not induce a fibrotic foreign body response. Pre-labeling of encapsulated MSCs with iron oxide nanoparticles allowed continued cell-tracking by MRI over several weeks following transplantation into infarcted myocardium. In contrast, MSCs injected as cell suspension were only detectable for two days post transplantation by MRI. Histological analysis confirmed integration of transplanted cells at the infarct site. Therefore, microcapsules proved to be suitable for stem cell delivery into the infarcted myocardium and can overcome current limitations of poor cell retention in cardiac cell-based therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

PubMed Central

Reis, Cesar; Wang, Yuechun; Akyol, Onat; Ho, Wing Mann; Applegate II, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

2015-01-01

Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI. PMID:26016501

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

NASA Astrophysics Data System (ADS)

Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

2015-04-01

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time.

Intracellular bimodal nanoparticles based on quantum dots for high-field MRI at 21.1 T.

PubMed

Rosenberg, Jens T; Kogot, Joshua M; Lovingood, Derek D; Strouse, Geoffrey F; Grant, Samuel C

2010-09-01

Multimodal, biocompatible contrast agents for high magnetic field applications represent a new class of nanomaterials with significant potential for tracking of fluorescence and MR in vitro and vivo. Optimized for high-field MR applications-including biomedical imaging at 21.1 T, the highest magnetic field available for MRI-these nanoparticles capitalize on the improved performance of chelated Dy(3+) with increasing magnetic field coupled to a noncytotoxic Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dot that provides fluorescence detection, MR responsiveness, and payload delivery. By surface modifying the quantum dot with a cell-penetrating peptide sequence coupled to an MR contrast agent, the bimodal nanomaterial functions as a self-transfecting high-field MR/optical contrast agent for nonspecific intracellular labeling. Fluorescent images confirm sequestration in perinuclear vesicles of labeled cells, with no apparent cytotoxicity. These techniques can be extended to impart cell selectivity or act as a delivery vehicle for genetic or pharmaceutical interventions. 2010 Wiley-Liss, Inc.

Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles.

PubMed

Connell, John J; Patrick, P Stephen; Yu, Yichao; Lythgoe, Mark F; Kalber, Tammy L

2015-01-01

Regenerative medicine would greatly benefit from a new platform technology that enabled measurable, controllable and targeting of stem cells to a site of disease or injury in the body. Superparamagnetic iron-oxide nanoparticles offer attractive possibilities in biomedicine and can be incorporated into cells, affording a safe and reliable means of tagging. This review describes three current and emerging methods to enhance regenerative medicine using magnetic particles to guide therapeutic cells to a target organ; track the cells using MRI and assess their spatial localization with high precision and influence the behavior of the cell using magnetic actuation. This approach is complementary to the systemic injection of cell therapies, thus expanding the horizon of stem cell therapeutics.

Gd-doped BNNTs as T2-weighted MRI contrast agents

NASA Astrophysics Data System (ADS)

Ciofani, Gianni; Boni, Adriano; Calucci, Lucia; Forte, Claudia; Gozzi, Alessandro; Mazzolai, Barbara; Mattoli, Virgilio

2013-08-01

This work describes, for the first time, doping of boron nitride nanotubes (BNNTs) with gadolinium (Gd@BNNTs), a stable functionalization that permits non-invasive BNNT tracking via magnetic resonance imaging (MRI). We report the structure, Gd loading, and relaxometric properties in water suspension at 7 T of Gd@BNNTs, and show the behaviour of these nanostructures as promising T2-weighted contrast agents. Finally, we demonstrate their complete biocompatibility in vitro on human neuroblastoma cells, together with their ability to effectively label and affect contrast in MRI images at 7 T.

In Vivo magnetic resonance imaging of xenografted tumors using FTH1 reporter gene expression controlled by a tet-on switch.

PubMed

He, Xiaoya; Cai, Jinhua; Li, Hao; Liu, Bo; Qin, Yong; Zhong, Yi; Wang, Longlun; Liao, Yifan

2016-11-29

As a promising magnetic resonance imaging (MRI) reporter, ferritin has been used to track cells in vivo; however, its continuous overexpression can be cytotoxic, which restricts its application. In this study, we aimed to develop a switch to turn this genetic reporter "on" or "off" while monitoring cell grafts via MRI. To accomplish this, we genetically modified the ferritin heavy chain (FTH1) with a Tet-On switch and assessed the expression of FTH1 in transduced neuroblastoma cells (SK-N-SH) in vitro and in xenografted tumors in vivo. We found that FTH1 expression induced by doxycycline (Dox) in SK-N-SH-FTH1 cells depended on treatment dose and duration. We successfully detected T2-weighted MRI contrast in cell grafts after switching "on" the reporter gene using Dox, and this contrast disappeared when we switched it "off". The genetic reporter FTH1 can thus be switched "on" or "off" throughout longitudinal monitoring of cell grafts, limiting expression to when MRI contrast is needed. The controllable imaging system we have developed minimizes risks from constitutive reporter gene overexpression and facilitates tumor cell monitoring in vitro and in vivo.

Polyelectrolyte coating of ferumoxytol nanoparticles for labeling of dendritic cells

NASA Astrophysics Data System (ADS)

Celikkin, Nehar; Jakubcová, Lucie; Zenke, Martin; Hoss, Mareike; Wong, John Erik; Hieronymus, Thomas

2015-04-01

Engineered magnetic nanoparticles (MNPs) are emerging to be used as cell tracers, drug delivery vehicles, and contrast agents for magnetic resonance imaging (MRI) for enhanced theragnostic applications in biomedicine. In vitro labeling of target cell populations with MNPs and their implantation into animal models and patients shows promising outcomes in monitoring successful cell engraftment, differentiation and migration by using MRI. Dendritic cells (DCs) are professional antigen-presenting cells that initiate adaptive immune responses. Thus, DCs have been the focus of cellular immunotherapy and are increasingly applied in clinical trials. Here, we addressed the coating of different polyelectrolytes (PE) around ferumoxytol particles using the layer-by-layer technique. The impact of PE-coated ferumoxytol particles for labeling of DCs and Flt3+ DC progenitors was then investigated. The results from our studies revealed that PE-coated ferumoxytol particles can be readily employed for labeling of DC and DC progenitors and thus are potentially suitable as contrast agents for MRI tracking.

Magnetic Particle / Magnetic Resonance Imaging: In-Vitro MPI-Guided Real Time Catheter Tracking and 4D Angioplasty Using a Road Map and Blood Pool Tracer Approach.

PubMed

Salamon, Johannes; Hofmann, Martin; Jung, Caroline; Kaul, Michael Gerhard; Werner, Franziska; Them, Kolja; Reimer, Rudolph; Nielsen, Peter; Vom Scheidt, Annika; Adam, Gerhard; Knopp, Tobias; Ittrich, Harald

2016-01-01

In-vitro evaluation of the feasibility of 4D real time tracking of endovascular devices and stenosis treatment with a magnetic particle imaging (MPI) / magnetic resonance imaging (MRI) road map approach and an MPI-guided approach using a blood pool tracer. A guide wire and angioplasty-catheter were labeled with a thin layer of magnetic lacquer. For real time MPI a custom made software framework was developed. A stenotic vessel phantom filled with saline or superparamagnetic iron oxide nanoparticles (MM4) was equipped with bimodal fiducial markers for co-registration in preclinical 7T MRI and MPI. In-vitro angioplasty was performed inflating the balloon with saline or MM4. MPI data were acquired using a field of view of 37.3×37.3×18.6 mm3 and a frame rate of 46 volumes/sec. Analysis of the magnetic lacquer-marks on the devices were performed with electron microscopy, atomic absorption spectrometry and micro-computed tomography. Magnetic marks allowed for MPI/MRI guidance of interventional devices. Bimodal fiducial markers enable MPI/MRI image fusion for MRI based roadmapping. MRI roadmapping and the blood pool tracer approach facilitate MPI real time monitoring of in-vitro angioplasty. Successful angioplasty was verified with MPI and MRI. Magnetic marks consist of micrometer sized ferromagnetic plates mainly composed of iron and iron oxide. 4D real time MP imaging, tracking and guiding of endovascular instruments and in-vitro angioplasty is feasible. In addition to an approach that requires a blood pool tracer, MRI based roadmapping might emerge as a promising tool for radiation free 4D MPI-guided interventions.

Tracking brain arousal fluctuations with fMRI

PubMed Central

Chang, Catie; Leopold, David A.; Schölvinck, Marieke Louise; Mandelkow, Hendrik; Picchioni, Dante; Liu, Xiao; Ye, Frank Q.; Turchi, Janita N.; Duyn, Jeff H.

2016-01-01

Changes in brain activity accompanying shifts in vigilance and arousal can interfere with the study of other intrinsic and task-evoked characteristics of brain function. However, the difficulty of tracking and modeling the arousal state during functional MRI (fMRI) typically precludes the assessment of arousal-dependent influences on fMRI signals. Here we combine fMRI, electrophysiology, and the monitoring of eyelid behavior to demonstrate an approach for tracking continuous variations in arousal level from fMRI data. We first characterize the spatial distribution of fMRI signal fluctuations that track a measure of behavioral arousal; taking this pattern as a template, and using the local field potential as a simultaneous and independent measure of cortical activity, we observe that the time-varying expression level of this template in fMRI data provides a close approximation of electrophysiological arousal. We discuss the potential benefit of these findings for increasing the sensitivity of fMRI as a cognitive and clinical biomarker. PMID:27051064

Siloxane nanoprobes for labeling and dual modality imaging of neural stem cells

PubMed Central

Addington, Caroline P.; Cusick, Alex; Shankar, Rohini Vidya; Agarwal, Shubhangi; Stabenfeldt, Sarah E.; Kodibagkar, Vikram D.

2015-01-01

Cell therapy represents a promising therapeutic for a myriad of medical conditions, including cancer, traumatic brain injury, and cardiovascular disease among others. A thorough understanding of the efficacy and cellular dynamics of these therapies necessitates the ability to non-invasively track cells in vivo. Magnetic resonance imaging (MRI) provides a platform to track cells as a non-invasive modality with superior resolution and soft tissue contrast. We recently reported a new nanoprobe platform for cell labeling and imaging using fluorophore doped siloxane core nanoemulsions as dual modality (1H MRI/Fluorescence), dual-functional (oximetry/detection) nanoprobes. Here, we successfully demonstrate the labeling, dual-modality imaging, and oximetry of neural progenitor/stem cells (NPSCs) in vitro using this platform. Labeling at a concentration of 10 μl/104 cells with a 40%v/v polydimethylsiloxane core nanoemulsion, doped with rhodamine, had minimal effect on viability, no effect on migration, proliferation and differentiation of NPSCs and allowed for unambiguous visualization of labeled NPSCs by 1H MR and fluorescence and local pO2 reporting by labeled NPSCs. This new approach for cell labeling with a positive contrast 1H MR probe has the potential to improve mechanistic knowledge of current therapies, and guide the design of future cell therapies due to its clinical translatability. PMID:26597417

Simple SPION Incubation as an Efficient Intracellular Labeling Method for Tracking Neural Progenitor Cells Using MRI

PubMed Central

D. M., Jayaseema; Lai, Jiann-Shiun; Hueng, Dueng-Yuan; Chang, Chen

2013-01-01

Cellular magnetic resonance imaging (MRI) has been well-established for tracking neural progenitor cells (NPC). Superparamagnetic iron oxide nanoparticles (SPIONs) approved for clinical application are the most common agents used for labeling. Conventionally, transfection agents (TAs) were added with SPIONs to facilitate cell labeling because SPIONs in the native unmodified form were deemed inefficient for intracellular labeling. However, compelling evidence also shows that simple SPION incubation is not invariably ineffective. The labeling efficiency can be improved by prolonged incubation and elevated iron doses. The goal of the present study was to establish simple SPION incubation as an efficient intracellular labeling method. To this end, NPCs derived from the neonatal subventricular zone were incubated with SPIONs (Feridex®) and then evaluated in vitro with regard to the labeling efficiency and biological functions. The results showed that, following 48 hours of incubation at 75 µg/ml, nearly all NPCs exhibited visible SPION intake. Evidence from light microscopy, electron microscopy, chemical analysis, and magnetic resonance imaging confirmed the effectiveness of the labeling. Additionally, biological assays showed that the labeled NPCs exhibited unaffected viability, oxidative stress, apoptosis and differentiation. In the demonstrated in vivo cellular MRI experiment, the hypointensities representing the SPION labeled NPCs remained observable throughout the entire tracking period. The findings indicate that simple SPION incubation without the addition of TAs is an efficient intracellular magnetic labeling method. This simple approach may be considered as an alternative approach to the mainstream labeling method that involves the use of TAs. PMID:23468856

A multimodality imaging model to track viable breast cancer cells from single arrest to metastasis in the mouse brain

PubMed Central

Parkins, Katie M.; Hamilton, Amanda M.; Makela, Ashley V.; Chen, Yuanxin; Foster, Paula J.; Ronald, John A.

2016-01-01

Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i.e., iron-loaded cells) on day 0 significantly correlated with BLI signal. Both BLI and MRI signals decreased from day 0 to day 8, indicating a loss of viable cells rather than a loss of iron label. Total brain MR tumour volume on day 28 also correlated with BLI signal. Overall, BLI complemented our sensitive cellular MRI technologies well, allowing us for the first time to screen animals for successful injections, and, in addition to MR measures of cell arrest and tumor burden, provided longitudinal measures of cancer cell viability in individual animals. We predict this novel multimodality molecular imaging framework will be useful for evaluating the efficacy of emerging anti-cancer drugs at different stages of the metastatic cascade. PMID:27767185

A multimodality imaging model to track viable breast cancer cells from single arrest to metastasis in the mouse brain.

PubMed

Parkins, Katie M; Hamilton, Amanda M; Makela, Ashley V; Chen, Yuanxin; Foster, Paula J; Ronald, John A

2016-10-21

Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i.e., iron-loaded cells) on day 0 significantly correlated with BLI signal. Both BLI and MRI signals decreased from day 0 to day 8, indicating a loss of viable cells rather than a loss of iron label. Total brain MR tumour volume on day 28 also correlated with BLI signal. Overall, BLI complemented our sensitive cellular MRI technologies well, allowing us for the first time to screen animals for successful injections, and, in addition to MR measures of cell arrest and tumor burden, provided longitudinal measures of cancer cell viability in individual animals. We predict this novel multimodality molecular imaging framework will be useful for evaluating the efficacy of emerging anti-cancer drugs at different stages of the metastatic cascade.

A multimodality imaging model to track viable breast cancer cells from single arrest to metastasis in the mouse brain

NASA Astrophysics Data System (ADS)

Parkins, Katie M.; Hamilton, Amanda M.; Makela, Ashley V.; Chen, Yuanxin; Foster, Paula J.; Ronald, John A.

2016-10-01

Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i.e., iron-loaded cells) on day 0 significantly correlated with BLI signal. Both BLI and MRI signals decreased from day 0 to day 8, indicating a loss of viable cells rather than a loss of iron label. Total brain MR tumour volume on day 28 also correlated with BLI signal. Overall, BLI complemented our sensitive cellular MRI technologies well, allowing us for the first time to screen animals for successful injections, and, in addition to MR measures of cell arrest and tumor burden, provided longitudinal measures of cancer cell viability in individual animals. We predict this novel multimodality molecular imaging framework will be useful for evaluating the efficacy of emerging anti-cancer drugs at different stages of the metastatic cascade.

Teleoperation System with Hybrid Pneumatic-Piezoelectric Actuation for MRI-Guided Needle Insertion with Haptic Feedback

PubMed Central

Shang, Weijian; Su, Hao; Li, Gang; Fischer, Gregory S.

2014-01-01

This paper presents a surgical master-slave tele-operation system for percutaneous interventional procedures under continuous magnetic resonance imaging (MRI) guidance. This system consists of a piezoelectrically actuated slave robot for needle placement with integrated fiber optic force sensor utilizing Fabry-Perot interferometry (FPI) sensing principle. The sensor flexure is optimized and embedded to the slave robot for measuring needle insertion force. A novel, compact opto-mechanical FPI sensor interface is integrated into an MRI robot control system. By leveraging the complementary features of pneumatic and piezoelectric actuation, a pneumatically actuated haptic master robot is also developed to render force associated with needle placement interventions to the clinician. An aluminum load cell is implemented and calibrated to close the impedance control loop of the master robot. A force-position control algorithm is developed to control the hybrid actuated system. Teleoperated needle insertion is demonstrated under live MR imaging, where the slave robot resides in the scanner bore and the user manipulates the master beside the patient outside the bore. Force and position tracking results of the master-slave robot are demonstrated to validate the tracking performance of the integrated system. It has a position tracking error of 0.318mm and sine wave force tracking error of 2.227N. PMID:25126446

Teleoperation System with Hybrid Pneumatic-Piezoelectric Actuation for MRI-Guided Needle Insertion with Haptic Feedback.

PubMed

Shang, Weijian; Su, Hao; Li, Gang; Fischer, Gregory S

2013-01-01

This paper presents a surgical master-slave tele-operation system for percutaneous interventional procedures under continuous magnetic resonance imaging (MRI) guidance. This system consists of a piezoelectrically actuated slave robot for needle placement with integrated fiber optic force sensor utilizing Fabry-Perot interferometry (FPI) sensing principle. The sensor flexure is optimized and embedded to the slave robot for measuring needle insertion force. A novel, compact opto-mechanical FPI sensor interface is integrated into an MRI robot control system. By leveraging the complementary features of pneumatic and piezoelectric actuation, a pneumatically actuated haptic master robot is also developed to render force associated with needle placement interventions to the clinician. An aluminum load cell is implemented and calibrated to close the impedance control loop of the master robot. A force-position control algorithm is developed to control the hybrid actuated system. Teleoperated needle insertion is demonstrated under live MR imaging, where the slave robot resides in the scanner bore and the user manipulates the master beside the patient outside the bore. Force and position tracking results of the master-slave robot are demonstrated to validate the tracking performance of the integrated system. It has a position tracking error of 0.318mm and sine wave force tracking error of 2.227N.

Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica Nanoparticles.

PubMed

Lee, Amani L; Gee, Clifford T; Weegman, Bradley P; Einstein, Samuel A; Juelfs, Adam R; Ring, Hattie L; Hurley, Katie R; Egger, Sam M; Swindlehurst, Garrett; Garwood, Michael; Pomerantz, William C K; Haynes, Christy L

2017-06-27

Oxygen homeostasis is important in the regulation of biological function. Disease progression can be monitored by measuring oxygen levels, thus producing information for the design of therapeutic treatments. Noninvasive measurements of tissue oxygenation require the development of tools with minimal adverse effects and facile detection of features of interest. Fluorine magnetic resonance imaging ( 19 F MRI) exploits the intrinsic properties of perfluorocarbon (PFC) liquids for anatomical imaging, cell tracking, and oxygen sensing. However, the highly hydrophobic and lipophobic properties of perfluorocarbons require the formation of emulsions for biological studies, though stabilizing these emulsions has been challenging. To enhance the stability and biological loading of perfluorocarbons, one option is to incorporate perfluorocarbon liquids into the internal space of biocompatible mesoporous silica nanoparticles. Here, we developed perfluorocarbon-loaded ultraporous mesostructured silica nanoparticles (PERFUMNs) as 19 F MRI detectable oxygen-sensing probes. Ultraporous mesostructured silica nanoparticles (UMNs) have large internal cavities (average = 1.8 cm 3 g -1 ), facilitating an average 17% loading efficiency of PFCs, meeting the threshold fluorine concentrations needed for imaging studies. Perfluoro-15-crown-5-ether PERFUMNs have the highest equivalent nuclei per PFC molecule and a spin-lattice (T 1 ) relaxation-based oxygen sensitivity of 0.0032 mmHg -1 s -1 at 16.4 T. The option of loading PFCs after synthesizing UMNs, rather than traditional in situ core-shell syntheses, allows for use of a broad range of PFC liquids from a single material. The biocompatible and tunable chemistry of UMNs combined with the intrinsic properties of PFCs makes PERFUMNs a MRI sensor with potential for anatomical imaging, cell tracking, and metabolic spectroscopy with improved stability.

Image to physical space registration of supine breast MRI for image guided breast surgery

NASA Astrophysics Data System (ADS)

Conley, Rebekah H.; Meszoely, Ingrid M.; Pheiffer, Thomas S.; Weis, Jared A.; Yankeelov, Thomas E.; Miga, Michael I.

2014-03-01

Breast conservation therapy (BCT) is a desirable option for many women diagnosed with early stage breast cancer and involves a lumpectomy followed by radiotherapy. However, approximately 50% of eligible women will elect for mastectomy over BCT despite equal survival benefit (provided margins of excised tissue are cancer free) due to uncertainty in outcome with regards to complete excision of cancerous cells, risk of local recurrence, and cosmesis. Determining surgical margins intraoperatively is difficult and achieving negative margins is not as robust as it needs to be, resulting in high re-operation rates and often mastectomy. Magnetic resonance images (MRI) can provide detailed information about tumor margin extents, however diagnostic images are acquired in a fundamentally different patient presentation than that used in surgery. Therefore, the high quality diagnostic MRIs taken in the prone position with pendant breast are not optimal for use in surgical planning/guidance due to the drastic shape change between preoperative images and the common supine surgical position. This work proposes to investigate the value of supine MRI in an effort to localize tumors intraoperatively using image-guidance. Mock intraoperative setups (realistic patient positioning in non-sterile environment) and preoperative imaging data were collected from a patient scheduled for a lumpectomy. The mock intraoperative data included a tracked laser range scan of the patient's breast surface, tracked center points of MR visible fiducials on the patient's breast, and tracked B-mode ultrasound and strain images. The preoperative data included a supine MRI with visible fiducial markers. Fiducial markers localized in the MRI were rigidly registered to their mock intraoperative counterparts using an optically tracked stylus. The root mean square (RMS) fiducial registration error using the tracked markers was 3.4mm. Following registration, the average closest point distance between the MR generated surface nodes and the LRS point cloud was 1.76±0.502 mm.

A Partnership Training Program: Studying Targeted Drug Delivery Using Nanoparticles in Breast Cancer Diagnosis and Therapy

DTIC Science & Technology

2013-10-01

labeling and tracking of mesenchymal stem cells (MSCs). MSCs are a heterogeneous group of pluripotent stromal cells that can be isolated from... mesenchymal stem cell labelling by using polyhedral superparamagnetic iron oxide nanoparticles. Chemistry 2009;15:12417-25. Wang and Shan. MRI cell ...and Differentiation of Mesenchymal Stem Cells by Carboxylated Carbon Nanotubes. ACS Nano 2010, 4, 2185–2195. 15. Bertoncini, P.; Chauvet, O

Three-dimensional liver motion tracking using real-time two-dimensional MRI

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

Brix, Lau, E-mail: lau.brix@stab.rm.dk; Ringgaard, Steffen; Sørensen, Thomas Sangild

2014-04-15

Purpose: Combined magnetic resonance imaging (MRI) systems and linear accelerators for radiotherapy (MR-Linacs) are currently under development. MRI is noninvasive and nonionizing and can produce images with high soft tissue contrast. However, new tracking methods are required to obtain fast real-time spatial target localization. This study develops and evaluates a method for tracking three-dimensional (3D) respiratory liver motion in two-dimensional (2D) real-time MRI image series with high temporal and spatial resolution. Methods: The proposed method for 3D tracking in 2D real-time MRI series has three steps: (1) Recording of a 3D MRI scan and selection of a blood vessel (ormore » tumor) structure to be tracked in subsequent 2D MRI series. (2) Generation of a library of 2D image templates oriented parallel to the 2D MRI image series by reslicing and resampling the 3D MRI scan. (3) 3D tracking of the selected structure in each real-time 2D image by finding the template and template position that yield the highest normalized cross correlation coefficient with the image. Since the tracked structure has a known 3D position relative to each template, the selection and 2D localization of a specific template translates into quantification of both the through-plane and in-plane position of the structure. As a proof of principle, 3D tracking of liver blood vessel structures was performed in five healthy volunteers in two 5.4 Hz axial, sagittal, and coronal real-time 2D MRI series of 30 s duration. In each 2D MRI series, the 3D localization was carried out twice, using nonoverlapping template libraries, which resulted in a total of 12 estimated 3D trajectories per volunteer. Validation tests carried out to support the tracking algorithm included quantification of the breathing induced 3D liver motion and liver motion directionality for the volunteers, and comparison of 2D MRI estimated positions of a structure in a watermelon with the actual positions. Results: Axial, sagittal, and coronal 2D MRI series yielded 3D respiratory motion curves for all volunteers. The motion directionality and amplitude were very similar when measured directly as in-plane motion or estimated indirectly as through-plane motion. The mean peak-to-peak breathing amplitude was 1.6 mm (left-right), 11.0 mm (craniocaudal), and 2.5 mm (anterior-posterior). The position of the watermelon structure was estimated in 2D MRI images with a root-mean-square error of 0.52 mm (in-plane) and 0.87 mm (through-plane). Conclusions: A method for 3D tracking in 2D MRI series was developed and demonstrated for liver tracking in volunteers. The method would allow real-time 3D localization with integrated MR-Linac systems.« less

[See the thinking brain: a story about water].

PubMed

Le Bihan, D

2008-01-01

Among the astonishing Einstein's papers from 1905, there is one which unexpectedly gave birth to a powerful method to explore the brain. Molecular diffusion was explained by Einstein on the basis of the random translational motion of molecules which results from their thermal energy. In the mid 1980s it was shown that water diffusion in the brain could be imaged using MRI. During their random displacements water molecules probe tissue structure at a microscopic scale, interacting with cell membranes and, thus, providing unique information on the functional architecture of tissues. A dramatic application of diffusion MRI has been brain ischemia, following the discovery that water diffusion drops immediately after the onset of an ischemic event, when brain cells undergo swelling through cytotoxic edema. On the other hand, water diffusion is anisotropic in white matter, because axon membranes limit molecular movement perpendicularly to the fibers. This feature can be exploited to map out the orientation in space of the white matter tracks and image brain connections. More recently, it has been shown that diffusion MRI could accurately detect cortical activation. As the diffusion response precedes by several seconds the hemodynamic response captured by BOLD fMRI, it has been suggested that water diffusion could reflect early neuronal events, such as the transient swelling of activated cortical cells. If confirmed, this discovery will represent a significant breakthrough, allowing non invasive access to a direct physiological marker of brain activation. This approach will bridge the gap between invasive optical imaging techniques in neuronal cell cultures, and current functional neuroimaging approaches in humans, which are based on indirect and remote blood flow changes.

Simultaneous tumor and surrogate motion tracking with dynamic MRI for radiation therapy planning

NASA Astrophysics Data System (ADS)

Park, Seyoun; Farah, Rana; Shea, Steven M.; Tryggestad, Erik; Hales, Russell; Lee, Junghoon

2018-01-01

Respiration-induced tumor motion is a major obstacle for achieving high-precision radiotherapy of cancers in the thoracic and abdominal regions. Surrogate-based estimation and tracking methods are commonly used in radiotherapy, but with limited understanding of quantified correlation to tumor motion. In this study, we propose a method to simultaneously track the lung tumor and external surrogates to evaluate their spatial correlation in a quantitative way using dynamic MRI, which allows real-time acquisition without ionizing radiation exposure. To capture the lung and whole tumor, four MRI-compatible fiducials are placed on the patient’s chest and upper abdomen. Two different types of acquisitions are performed in the sagittal orientation including multi-slice 2D cine MRIs to reconstruct 4D-MRI and two-slice 2D cine MRIs to simultaneously track the tumor and fiducials. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and groupwise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D-2D template matching in which 3D tumor templates in the 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model of the fiducials to their segmentations on the 2D cine MRIs. We tested our method on ten lung cancer patients. Using a correlation analysis, the 3D tumor trajectory demonstrates a noticeable phase mismatch and significant cycle-to-cycle motion variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from the fiducials at different locations.

Evaluation of the specificity and sensitivity of ferritin as an MRI reporter gene in the mouse brain using lentiviral and adeno-associated viral vectors.

PubMed

Vande Velde, G; Rangarajan, J R; Toelen, J; Dresselaers, T; Ibrahimi, A; Krylychkina, O; Vreys, R; Van der Linden, A; Maes, F; Debyser, Z; Himmelreich, U; Baekelandt, V

2011-06-01

The development of in vivo imaging protocols to reliably track transplanted cells or to report on gene expression is critical for treatment monitoring in (pre)clinical cell and gene therapy protocols. Therefore, we evaluated the potential of lentiviral vectors (LVs) and adeno-associated viral vectors (AAVs) to express the magnetic resonance imaging (MRI) reporter gene ferritin in the rodent brain. First, we compared the induction of background MRI contrast for both vector systems in immune-deficient and immune-competent mice. LV injection resulted in hypointense (that is, dark) changes of T(2)/T(2)(*) (spin-spin relaxation time)-weighted MRI contrast at the injection site, which can be partially explained by an inflammatory response against the vector injection. In contrast to LVs, AAV injection resulted in reduced background contrast. Moreover, AAV-mediated ferritin overexpression resulted in significantly enhanced contrast to background on T(2)(*)-weighted MRI. Although sensitivity associated with the ferritin reporter remains modest, AAVs seem to be the most promising vector system for in vivo MRI reporter gene imaging.

Accelerating volumetric cine MRI (VC-MRI) using undersampling for real-time 3D target localization/tracking in radiation therapy: a feasibility study

NASA Astrophysics Data System (ADS)

Harris, Wendy; Yin, Fang-Fang; Wang, Chunhao; Zhang, You; Cai, Jing; Ren, Lei

2018-01-01

Purpose. To accelerate volumetric cine MRI (VC-MRI) using undersampled 2D-cine MRI to provide real-time 3D guidance for gating/target tracking in radiotherapy. Methods. 4D-MRI is acquired during patient simulation. One phase of the prior 4D-MRI is selected as the prior images, designated as MRIprior. The on-board VC-MRI at each time-step is considered a deformation of the MRIprior. The deformation field map is represented as a linear combination of the motion components extracted by principal component analysis from the prior 4D-MRI. The weighting coefficients of the motion components are solved by matching the corresponding 2D-slice of the VC-MRI with the on-board undersampled 2D-cine MRI acquired. Undersampled Cartesian and radial k-space acquisition strategies were investigated. The effects of k-space sampling percentage (SP) and distribution, tumor sizes and noise on the VC-MRI estimation were studied. The VC-MRI estimation was evaluated using XCAT simulation of lung cancer patients and data from liver cancer patients. Volume percent difference (VPD) and Center of Mass Shift (COMS) of the tumor volumes and tumor tracking errors were calculated. Results. For XCAT, VPD/COMS were 11.93  ±  2.37%/0.90  ±  0.27 mm and 11.53  ±  1.47%/0.85  ±  0.20 mm among all scenarios with Cartesian sampling (SP  =  10%) and radial sampling (21 spokes, SP  =  5.2%), respectively. When tumor size decreased, higher sampling rate achieved more accurate VC-MRI than lower sampling rate. VC-MRI was robust against noise levels up to SNR  =  20. For patient data, the tumor tracking errors in superior-inferior, anterior-posterior and lateral (LAT) directions were 0.46  ±  0.20 mm, 0.56  ±  0.17 mm and 0.23  ±  0.16 mm, respectively, for Cartesian-based sampling with SP  =  20% and 0.60  ±  0.19 mm, 0.56  ±  0.22 mm and 0.42  ±  0.15 mm, respectively, for radial-based sampling with SP  =  8% (32 spokes). Conclusions. It is feasible to estimate VC-MRI from a single undersampled on-board 2D cine MRI. Phantom and patient studies showed that the temporal resolution of VC-MRI can potentially be improved by 5-10 times using a 2D cine image acquired with 10-20% k-space sampling.

Cryopreservation of embryonic stem cell-derived multicellular neural aggregates labeled with micron-sized particles of iron oxide for magnetic resonance imaging.

PubMed

Yan, Yuanwei; Sart, Sébastien; Calixto Bejarano, Fabian; Muroski, Megan E; Strouse, Geoffrey F; Grant, Samuel C; Li, Yan

2015-01-01

Magnetic resonance imaging (MRI) provides an effective approach to track labeled pluripotent stem cell (PSC)-derived neural progenitor cells (NPCs) for neurological disorder treatments after cell labeling with a contrast agent, such as an iron oxide derivative. Cryopreservation of pre-labeled neural cells, especially in three-dimensional (3D) structure, can provide a uniform cell population and preserve the stem cell niche for the subsequent applications. In this study, the effects of cryopreservation on PSC-derived multicellular NPC aggregates labeled with micron-sized particles of iron oxide (MPIO) were investigated. These NPC aggregates were labeled prior to cryopreservation because labeling thawed cells can be limited by inefficient intracellular uptake, variations in labeling efficiency, and increased culture time before use, minimizing their translation to clinical settings. The results indicated that intracellular MPIO incorporation was retained after cryopreservation (70-80% labeling efficiency), and MPIO labeling had little adverse effects on cell recovery, proliferation, cytotoxicity and neural lineage commitment post-cryopreservation. MRI analysis showed comparable detectability for the MPIO-labeled cells before and after cryopreservation indicated by T2 and T2* relaxation rates. Cryopreserving MPIO-labeled 3D multicellular NPC aggregates can be applied in in vivo cell tracking studies and lead to more rapid translation from preservation to clinical implementation. © 2015 American Institute of Chemical Engineers.

In Vivo MR Imaging of Dual MRI Reporter Genes and Deltex-1 Gene-modified Human Mesenchymal Stem Cells in the Treatment of Closed Penile Fracture.

PubMed

Guo, Ruomi; Li, Qingling; Yang, Fei; Hu, Xiaojun; Jiao, Ju; Guo, Yu; Wang, Jin; Zhang, Yong

2018-06-01

The purpose of this study was to investigate the feasibility of dual magnetic resonance imaging (MRI) reporter genes, including ferritin heavy subunit (Fth) and transferrin receptor (TfR), which provide sufficient MRI contrast for in vivo MRI tracking, and the Deltex-1 (DTX1) gene, which promotes human mesenchymal stem cell (hMSC) differentiation to smooth muscle cells (SMCs), to treat closed penile fracture (CPF). Multi-gene co-expressing hMSCs were generated. The expression of mRNA and proteins was assessed, and the original biological properties of hMSCs were determined and compared. The intracellular uptake of iron was evaluated, and the ability to differentiate into SMCs was detected. Fifty rabbits with CPF were randomly transplanted with PBS, hMSCs, Fth-TfR-hMSCs, DTX1-hMSCs, and Fth-TfR-DTX1-hMSCs. In vivo MRI was performed to detect the distribution and migration of the grafted cells and healing progress of CPF, and the results were correlated with histology. The mRNA and proteins of the multi-gene were highly expressed. The transgenes could not influence the original biological properties of hMSCs. The dual MRI reporter genes increased the iron accumulation capacity, and the DTX1 gene promoted hMSC differentiation into SMCs. The distribution and migration of the dual MRI reporter gene-modified hMSCs, and the healing state of CPF could be obviously detected by MRI and confirmed by histology. The dual MRI reporter genes could provide sufficient MRI contrast, and the distribution and migration of MSCs could be detected in vivo. The DTX1 gene can promote MSC differentiation into SMCs for the treatment of CPF and effectively inhibit granulation tissue formation.

In vivo and ex vivo 19-fluorine magnetic resonance imaging and spectroscopy of beta-cells and pancreatic islets using GLUT-2 specific contrast agents.

PubMed

Liang, Sayuan; Louchami, Karim; Kolster, Hauke; Jacobsen, Anna; Zhang, Ying; Thimm, Julian; Sener, Abdullah; Thiem, Joachim; Malaisse, Willy; Dresselaers, Tom; Himmelreich, Uwe

2016-11-01

The assessment of the β-cell mass in experimental models of diabetes and ultimately in patients is a hallmark to understand the relationship between reduced β-cell mass/function and the onset of diabetes. It has been shown before that the GLUT-2 transporter is highly expressed in both β-cells and hepatocytes and that D-mannoheptulose (DMH) has high uptake specificity for the GLUT-2 transporter. As 19-fluorine MRI has emerged as a new alternative method for MRI cell tracking because it provides potential non-invasive localization and quantification of labeled cells, the purpose of this project is to validate β-cell and pancreatic islet imaging by using fluorinated, GLUT-2 targeting mannoheptulose derivatives ( 19 FMH) both in vivo and ex vivo. In this study, we confirmed that, similar to DMH, 19 FMHs inhibit insulin secretion and increase the blood glucose level in mice temporarily (approximately two hours). We were able to assess the distribution of 19 FMHs in vivo with a temporal resolution of about 20 minutes, which showed a quick removal of 19 FMH from the circulation (within two hours). Ex vivo MR spectroscopy confirmed a preferential uptake of 19 FMH in tissue with high expression of the GLUT-2 transporter, such as liver, endocrine pancreas and kidney. No indication of further metabolism was found. In summary, 19 FMHs are potentially suitable for visualizing and tracking of GLUT-2 expressed cells. However, current bottlenecks of this technique related to the quick clearance of the compound and relative low sensitivity of 19 F MRI need to be overcome. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

TU-F-BRB-00: MRI-Based Motion Management for RT

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

NONE

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

PubMed

Angelovski, Goran; Gottschalk, Sven; Milošević, Milena; Engelmann, Jörn; Hagberg, Gisela E; Kadjane, Pascal; Andjus, Pavle; Logothetis, Nikos K

2014-05-21

Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca(2+)-sensitive, Gd(3+)-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca(2+) showed that, despite a reduction in the Ca(2+) level, transport of Ca(2+) through the plasma membrane remained unaffected, while stimulation with ATP induced Ca(2+)-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca(2+) level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca(2+) concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1-6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level.

Magnetic Particle Imaging (MPI) for NMR and MRI researchers

NASA Astrophysics Data System (ADS)

Saritas, Emine U.; Goodwill, Patrick W.; Croft, Laura R.; Konkle, Justin J.; Lu, Kuan; Zheng, Bo; Conolly, Steven M.

2013-04-01

Magnetic Particle Imaging (MPI) is a new tracer imaging modality that is gaining significant interest from NMR and MRI researchers. While the physics of MPI differ substantially from MRI, it employs hardware and imaging concepts that are familiar to MRI researchers, such as magnetic excitation and detection, pulse sequences, and relaxation effects. Furthermore, MPI employs the same superparamagnetic iron oxide (SPIO) contrast agents that are sometimes used for MR angiography and are often used for MRI cell tracking studies. These SPIOs are much safer for humans than iodine or gadolinium, especially for Chronic Kidney Disease (CKD) patients. The weak kidneys of CKD patients cannot safely excrete iodine or gadolinium, leading to increased morbidity and mortality after iodinated X-ray or CT angiograms, or after gadolinium-MRA studies. Iron oxides, on the other hand, are processed in the liver, and have been shown to be safe even for CKD patients. Unlike the “black blood” contrast generated by SPIOs in MRI due to increased T2∗ dephasing, SPIOs in MPI generate positive, “bright blood” contrast. With this ideal contrast, even prototype MPI scanners can already achieve fast, high-sensitivity, and high-contrast angiograms with millimeter-scale resolutions in phantoms and in animals. Moreover, MPI shows great potential for an exciting array of applications, including stem cell tracking in vivo, first-pass contrast studies to diagnose or stage cancer, and inflammation imaging in vivo. So far, only a handful of prototype small-animal MPI scanners have been constructed worldwide. Hence, MPI is open to great advances, especially in hardware, pulse sequence, and nanoparticle improvements, with the potential to revolutionize the biomedical imaging field.

Magnetic Resonance Imaging of Chondrocytes Labeled with Superparamagnetic Iron Oxide Nanoparticles in Tissue-Engineered Cartilage

PubMed Central

Ramaswamy, Sharan; Greco, Jane B.; Uluer, Mehmet C.; Zhang, Zijun; Zhang, Zhuoli; Fishbein, Kenneth W.

2009-01-01

The distribution of cells within tissue-engineered constructs is difficult to study through nondestructive means, such as would be required after implantation. However, cell labeling with iron-containing particles may prove to be a useful approach to this problem, because regions containing such labeled cells have been shown to be readily detectable using magnetic resonance imaging (MRI). In this study, we used the Food and Drug Administration–approved superparamagnetic iron oxide (SPIO) contrast agent Feridex in combination with transfection agents to label chondrocytes and visualize them with MRI in two different tissue-engineered cartilage constructs. Correspondence between labeled cell spatial location as determined using MRI and histology was established. The SPIO-labeling process was found not to affect the phenotype or viability of the chondrocytes or the production of major cartilage matrix constituents. We believe that this method of visualizing and tracking chondrocytes may be useful in the further development of tissue engineered cartilage therapeutics. PMID:19788362

An MRI-Compatible Robotic System With Hybrid Tracking for MRI-Guided Prostate Intervention

PubMed Central

Krieger, Axel; Iordachita, Iulian I.; Guion, Peter; Singh, Anurag K.; Kaushal, Aradhana; Ménard, Cynthia; Pinto, Peter A.; Camphausen, Kevin; Fichtinger, Gabor

2012-01-01

This paper reports the development, evaluation, and first clinical trials of the access to the prostate tissue (APT) II system—a scanner independent system for magnetic resonance imaging (MRI)-guided transrectal prostate interventions. The system utilizes novel manipulator mechanics employing a steerable needle channel and a novel six degree-of-freedom hybrid tracking method, comprising passive fiducial tracking for initial registration and subsequent incremental motion measurements. Targeting accuracy of the system in prostate phantom experiments and two clinical human-subject procedures is shown to compare favorably with existing systems using passive and active tracking methods. The portable design of the APT II system, using only standard MRI image sequences and minimal custom scanner interfacing, allows the system to be easily used on different MRI scanners. PMID:22009867

TU-F-BRB-02: Motion Artifacts and Suppression in MRI

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

Zhong, X.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

TU-F-BRB-01: Resolving and Characterizing Breathing Motion for Radiotherapy with MRI

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

Tryggestad, E.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

Magnetic vesicles as MRI-trackable biogenic nanovectors

NASA Astrophysics Data System (ADS)

Andriola Silva, Amanda K.; Luciani, Nathalie; Gazeau, Florence; Wilhelm, Claire

2012-03-01

Magnetic labeling renders cells MRI-detectable which provides attractive solutions for tracking the fate of a transplanted cell population. Understanding the interplay of magnetic nanoparticles and cells is then an important point that should not be neglected. Here we show that in the condition of food starvation, macrophage cells emit vesicles containing nanoparticles. First, we inferred the intracellular iron oxide load from the magnetophoretic velocity of cells at a calibrated magnetic field gradient. After magnetic labeling and culture in stress conditions, the intracellular iron oxide load was once more determined and a detectable difference was observed before and after stress. Moreover, we identified in the stress conditioned medium membrane vesicle structures carrying magnetic particles. Besides pointing out the role of cell-derived vesicles in the sequestration of the intracellular magnetic label, experiments also demonstrated that vesicles were able to chaperone the magnetic cargo into naïve cells.

A novel AIF tracking method and comparison of DCE-MRI parameters using individual and population-based AIFs in human breast cancer

NASA Astrophysics Data System (ADS)

Li, Xia; Welch, E. Brian; Arlinghaus, Lori R.; Bapsi Chakravarthy, A.; Xu, Lei; Farley, Jaime; Loveless, Mary E.; Mayer, Ingrid A.; Kelley, Mark C.; Meszoely, Ingrid M.; Means-Powell, Julie A.; Abramson, Vandana G.; Grau, Ana M.; Gore, John C.; Yankeelov, Thomas E.

2011-09-01

Quantitative analysis of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data requires the accurate determination of the arterial input function (AIF). A novel method for obtaining the AIF is presented here and pharmacokinetic parameters derived from individual and population-based AIFs are then compared. A Philips 3.0 T Achieva MR scanner was used to obtain 20 DCE-MRI data sets from ten breast cancer patients prior to and after one cycle of chemotherapy. Using a semi-automated method to estimate the AIF from the axillary artery, we obtain the AIF for each patient, AIFind, and compute a population-averaged AIF, AIFpop. The extended standard model is used to estimate the physiological parameters using the two types of AIFs. The mean concordance correlation coefficient (CCC) for the AIFs segmented manually and by the proposed AIF tracking approach is 0.96, indicating accurate and automatic tracking of an AIF in DCE-MRI data of the breast is possible. Regarding the kinetic parameters, the CCC values for Ktrans, vp and ve as estimated by AIFind and AIFpop are 0.65, 0.74 and 0.31, respectively, based on the region of interest analysis. The average CCC values for the voxel-by-voxel analysis are 0.76, 0.84 and 0.68 for Ktrans, vp and ve, respectively. This work indicates that Ktrans and vp show good agreement between AIFpop and AIFind while there is a weak agreement on ve.

Radio-frequency energy quantification in magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Alon, Leeor

Mapping of radio frequency (RF) energy deposition has been challenging for 50+ years, especially, when scanning patients in the magnetic resonance imaging (MRI) environment. As result, electromagnetic simulation software is often used for estimating the specific absorption rate (SAR), the rate of RF energy deposition in tissue. The thesis work presents challenges associated with aligning information provided by electromagnetic simulation and MRI experiments. As result of the limitations of simulations, experimental methods for the quantification of SAR were established. A system for quantification of the total RF energy deposition was developed for parallel transmit MRI (a system that uses multiple antennas to excite and image the body). The system is capable of monitoring and predicting channel-by-channel RF energy deposition, whole body SAR and capable of tracking potential hardware failures that occur in the transmit chain and may cause the deposition of excessive energy into patients. Similarly, we demonstrated that local RF power deposition can be mapped and predicted for parallel transmit systems based on a series of MRI temperature mapping acquisitions. Resulting from the work, we developed tools for optimal reconstruction temperature maps from MRI acquisitions. The tools developed for temperature mapping paved the way for utilizing MRI as a diagnostic tool for evaluation of RF/microwave emitting device safety. Quantification of the RF energy was demonstrated for both MRI compatible and non-MRI-compatible devices (such as cell phones), while having the advantage of being noninvasive, of providing millimeter resolution and high accuracy.

TU-F-BRB-03: Clinical Implementation of MR-Based Motion Management

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

Glide-Hurst, C.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

MRI-guided tumor tracking in lung cancer radiotherapy

NASA Astrophysics Data System (ADS)

Cerviño, Laura I.; Du, Jiang; Jiang, Steve B.

2011-07-01

Precise tracking of lung tumor motion during treatment delivery still represents a challenge in radiation therapy. Prototypes of MRI-linac hybrid systems are being created which have the potential of ionization-free real-time imaging of the tumor. This study evaluates the performance of lung tumor tracking algorithms in cine-MRI sagittal images from five healthy volunteers. Visible vascular structures were used as targets. Volunteers performed several series of regular and irregular breathing. Two tracking algorithms were implemented and evaluated: a template matching (TM) algorithm in combination with surrogate tracking using the diaphragm (surrogate was used when the maximum correlation between the template and the image in the search window was less than specified), and an artificial neural network (ANN) model based on the principal components of a region of interest that encompasses the target motion. The mean tracking error ē and the error at 95% confidence level e95 were evaluated for each model. The ANN model led to ē = 1.5 mm and e95 = 4.2 mm, while TM led to ē = 0.6 mm and e95 = 1.0 mm. An extra series was considered separately to evaluate the benefit of using surrogate tracking in combination with TM when target out-of-plane motion occurs. For this series, the mean error was 7.2 mm using only TM and 1.7 mm when the surrogate was used in combination with TM. Results show that, as opposed to tracking with other imaging modalities, ANN does not perform well in MR-guided tracking. TM, however, leads to highly accurate tracking. Out-of-plane motion could be addressed by surrogate tracking using the diaphragm, which can be easily identified in the images.

Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?

PubMed Central

Tang, Catherine; Russell, Pamela J; Martiniello-Wilks, Rosetta; J Rasko, John E; Khatri, Aparajita

2010-01-01

Ineffective treatment and poor patient management continue to plague the arena of clinical oncology. The crucial issues include inadequate treatment efficacy due to ineffective targeting of cancer deposits, systemic toxicities, suboptimal cancer detection and disease monitoring. This has led to the quest for clinically relevant, innovative multifaceted solutions such as development of targeted and traceable therapies. Mesenchymal stem cells (MSCs) have the intrinsic ability to “home” to growing tumors and are hypoimmunogenic. Therefore, these can be used as (a) “Trojan Horses” to deliver gene therapy directly into the tumors and (b) carriers of nanoparticles to allow cell tracking and simultaneous cancer detection. The camouflage of MSC carriers can potentially tackle the issues of safety, vector, and/or transgene immunogenicity as well as nanoparticle clearance and toxicity. The versatility of the nanotechnology platform could allow cellular tracking using single or multimodal imaging modalities. Toward that end, noninvasive magnetic resonance imaging (MRI) is fast becoming a clinical favorite, though there is scope for improvement in its accuracy and sensitivity. In that, use of superparamagnetic iron-oxide nanoparticles (SPION) as MRI contrast enhancers may be the best option for tracking therapeutic MSC. The prospects and consequences of synergistic approaches using MSC carriers, gene therapy, and SPION in developing cancer diagnostics and therapeutics are discussed. STEM CELLS 2010; 28:1686–1702. PMID:20629172

Migration of iron-labeled KHYG-1 natural killer cells to subcutaneous tumors in nude mice, as detected by magnetic resonance imaging.

PubMed

Mallett, Christiane L; McFadden, Catherine; Chen, Yuhua; Foster, Paula J

2012-07-01

A novel cell line of cytotoxic natural killer (NK) cells, KHYG-1, was examined in vivo for immunotherapy against prostate cancer. The feasibility of using magnetic resonance imaging (MRI) tracking to monitor the fate of injected NK cells following intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c.) administration was assessed. PC-3M human prostate cancer cells were injected s.c. into the flank of nude mice (day 0). KHYG-1 NK cells were labeled with an iron oxide contrast agent and injected s.c., i.v. or i.p. on day 8. Mice were imaged by MRI on days 7, 9 and 12. Tumor sections were examined with fluorescence microscopy and immunohistologic staining for NK cells. NK cells were detected in the tumors by histology after all three administration routes. NK cells and fluorescence from the iron label were co-localized. Signal loss was seen in the areas around the tumors and between the tumor lobes in the s.c. group. We are the first to label this cell line of NK cells with an iron oxide contrast agent. Accumulation of NK cells was visualized by MRI after s.c. injection but not after i.v. and i.p. injection.

Biological and MRI characterization of biomimetic ECM scaffolds for cartilage tissue regeneration.

PubMed

Ravindran, Sriram; Kotecha, Mrignayani; Huang, Chun-Chieh; Ye, Allen; Pothirajan, Padmabharathi; Yin, Ziying; Magin, Richard; George, Anne

2015-12-01

Osteoarthritis is the most common joint disorder affecting millions of people. Most scaffolds developed for cartilage regeneration fail due to vascularization and matrix mineralization. In this study we present a chondrogenic extracellular matrix (ECM) incorporated collagen/chitosan scaffold (chondrogenic ECM scaffold) for potential use in cartilage regenerative therapy. Biochemical characterization showed that these scaffolds possess key pro-chondrogenic ECM components and growth factors. MRI characterization showed that the scaffolds possess mechanical properties and diffusion characteristics important for cartilage tissue regeneration. In vivo implantation of the chondrogenic ECM scaffolds with bone marrow derived mesenchymal stem cells (MSCs) triggered chondrogenic differentiation of the MSCs without the need for external stimulus. Finally, results from in vivo MRI experiments indicate that the chondrogenic ECM scaffolds are stable and possess MR properties on par with native cartilage. Based on our results, we envision that such ECM incorporated scaffolds have great potential in cartilage regenerative therapy. Additionally, our validation of MR parameters with histology and biochemical analysis indicates the ability of MRI techniques to track the progress of our ECM scaffolds non-invasively in vivo; highlighting the translatory potential of this technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

TU-PIS-Exhibit Hall-2: How to Move Beyond Dose Monitoring to Imaging Performance Utilization

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

Valencia, D.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

TU-PIS-Exhibit Hall-4: How to implement a dose monitoring solution in the real world: a technical perspective

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

Massey, S.

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

TU-PIS-Exhibit Hall-1: Tools for Collecting and Analyzing Patient Dose Index Information from Imaging Equipment

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

Wang, J.; Stanford University: Introduction

The current clinical standard of organ respiratory imaging, 4D-CT, is fundamentally limited by poor soft-tissue contrast and imaging dose. These limitations are potential barriers to beneficial “4D” radiotherapy methods which optimize the target and OAR dose-volume considering breathing motion but rely on a robust motion characterization. Conversely, MRI imparts no known radiation risk and has excellent soft-tissue contrast. MRI-based motion management is therefore highly desirable and holds great promise to improve radiotherapy of moving cancers, particularly in the abdomen. Over the past decade, MRI techniques have improved significantly, making MR-based motion management clinically feasible. For example, cine MRI has highmore » temporal resolution up to 10 f/s and has been used to track and/or characterize tumor motion, study correlation between external and internal motions. New MR technologies, such as 4D-MRI and MRI hybrid treatment machines (i.e. MR-linac or MR-Co60), have been recently developed. These technologies can lead to more accurate target volume determination and more precise radiation dose delivery via direct tumor gating or tracking. Despite all these promises, great challenges exist and the achievable clinical benefit of MRI-based tumor motion management has yet to be fully explored, much less realized. In this proposal, we will review novel MR-based motion management methods and technologies, the state-of-the-art concerning MRI development and clinical application and the barriers to more widespread adoption. Learning Objectives: Discuss the need of MR-based motion management for improving patient care in radiotherapy. Understand MR techniques for motion imaging and tumor motion characterization. Understand the current state of the art and future steps for clinical integration. Henry Ford Health System holds research agreements with Philips Healthcare. Research sponsored in part by a Henry Ford Health System Internal Mentored Grant.« less

PROMO – Real-time Prospective Motion Correction in MRI using Image-based Tracking

PubMed Central

White, Nathan; Roddey, Cooper; Shankaranarayanan, Ajit; Han, Eric; Rettmann, Dan; Santos, Juan; Kuperman, Josh; Dale, Anders

2010-01-01

Artifacts caused by patient motion during scanning remain a serious problem in most MRI applications. The prospective motion correction technique attempts to address this problem at its source by keeping the measurement coordinate system fixed with respect to the patient throughout the entire scan process. In this study, a new image-based approach for prospective motion correction is described, which utilizes three orthogonal 2D spiral navigator acquisitions (SP-Navs) along with a flexible image-based tracking method based on the Extended Kalman Filter (EKF) algorithm for online motion measurement. The SP-Nav/EKF framework offers the advantages of image-domain tracking within patient-specific regions-of-interest and reduced sensitivity to off-resonance-induced corruption of rigid-body motion estimates. The performance of the method was tested using offline computer simulations and online in vivo head motion experiments. In vivo validation results covering a broad range of staged head motions indicate a steady-state error of the SP-Nav/EKF motion estimates of less than 10 % of the motion magnitude, even for large compound motions that included rotations over 15 degrees. A preliminary in vivo application in 3D inversion recovery spoiled gradient echo (IR-SPGR) and 3D fast spin echo (FSE) sequences demonstrates the effectiveness of the SP-Nav/EKF framework for correcting 3D rigid-body head motion artifacts prospectively in high-resolution 3D MRI scans. PMID:20027635

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation.

PubMed

Umashankar, Abhishek; Corenblum, Mandi J; Ray, Sneha; Valdez, Michel; Yoshimaru, Eriko S; Trouard, Theodore P; Madhavan, Lalitha

2016-01-01

An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB), which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 μg/mL) were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 μg/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 μg/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 μg/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68(+)-activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an exaggerated MRI signal dropout in the animals. Overall, these results indicate that although USPIO particles, such as MIRB, may have advantageous labeling and magnetic resonance-sensitive features for NSC tracking, a further examination of their effects might be necessary before they can be used in clinical scenarios of cell-based transplantation.

Structural and functional changes during epileptogenesis in the mouse model of medial temporal lobe epilepsy.

PubMed

Dietrich, Yvan; Eliat, Pierre-Antoine; Dieuset, Gabriel; Saint-Jalmes, Herve; Pineau, Charles; Wendling, Fabrice; Martin, Benoit

2016-08-01

An important issue in epilepsy research is to understand the structural and functional modifications leading to chronic epilepsy, characterized by spontaneous recurrent seizures, after initial brain insult. To address this issue, we recorded and analyzed electroencephalography (EEG) and quantitative magnetic resonance imaging (MRI) data during epileptogenesis in the in vivo mouse model of Medial Temporal Lobe Epilepsy (MTLE, kainate). Besides, this model of epilepsy is a particular form of drug-resistant epilepsy. The results indicate that high-field (4.7T) MRI parameters (T2-weighted; T2-quantitative) allow to detect the gradual neuro-anatomical changes that occur during epileptogenesis while electrophysiological parameters (number and duration of Hippocampal Paroxysmal Discharges) allow to assess the dysfunctional changes through the quantification of epileptiform activity. We found a strong correlation between EEG-based markers (invasive recording) and MRI-based parameters (non-invasive) periodically computed over the `latent period' that spans over two weeks, on average. These results indicated that both structural and functional changes occur in the considered epilepsy model and are considered as biomarkers of the installation of epilepsy. Additionally, such structural and functional changes can also be observed in human temporal lobe epilepsy. Interestingly, MRI imaging parameters could be used to track early (day-7) structural changes (gliosis, cell loss) in the lesioned brain and to quantify the evolution of epileptogenesis after traumatic brain injury.

Quantifying Post- Laser Ablation Prostate Therapy Changes on MRI via a Domain-Specific Biomechanical Model: Preliminary Findings

PubMed Central

Toth, Robert; Sperling, Dan; Madabhushi, Anant

2016-01-01

Focal laser ablation destroys cancerous cells via thermal destruction of tissue by a laser. Heat is absorbed, causing thermal necrosis of the target region. It combines the aggressive benefits of radiation treatment (destroying cancer cells) without the harmful side effects (due to its precise localization). MRI is typically used pre-treatment to determine the targeted area, and post-treatment to determine efficacy by detecting necrotic tissue, or tumor recurrence. However, no system exists to quantitatively evaluate the post-treatment effects on the morphology and structure via MRI. To quantify these changes, the pre- and post-treatment MR images must first be spatially aligned. The goal is to quantify (a) laser-induced shape-based changes, and (b) changes in MRI parameters post-treatment. The shape-based changes may be correlated with treatment efficacy, and the quantitative effects of laser treatment over time is currently poorly understood. This work attempts to model changes in gland morphology following laser treatment due to (1) patient alignment, (2) changes due to surrounding organs such as the bladder and rectum, and (3) changes due to the treatment itself. To isolate the treatment-induced shape-based changes, the changes from (1) and (2) are first modeled and removed using a finite element model (FEM). A FEM models the physical properties of tissue. The use of a physical biomechanical model is important since a stated goal of this work is to determine the physical shape-based changes to the prostate from the treatment, and therefore only physical real deformations are to be allowed. A second FEM is then used to isolate the physical, shape-based, treatment-induced changes. We applied and evaluated our model in capturing the laser induced changes to the prostate morphology on eight patients with 3.0 Tesla, T2-weighted MRI, acquired approximately six months following treatment. Our results suggest the laser treatment causes a decrease in prostate volume, which appears to manifest predominantly at the site of ablation. After spatially aligning the images, changes to MRI intensity values are clearly visible at the site of ablation. Our results suggest that our new methodology is able to capture and quantify the degree of laser-induced changes to the prostate. The quantitative measurements reflecting of the deformation changes can be used to track treatment response over time. PMID:27088600

Integrated Eye Tracking and Neural Monitoring for Enhanced Assessment of Mild TBI

DTIC Science & Technology

2016-04-01

and we anticipate the initiation of the neuroimaging portion of the study early in Year 3. The fMRI task has been completed and is in beta testing...neurocognitive test battery, and self-report measures of cognitive efficacy. We will also include functional magnetic resonance imagining ( fMRI ) and... fMRI and DTI will provide an objective basis for cross-validating the EEG and eye tracking system. Both the EEG and eye tracking data will be

A Hough Transform Global Probabilistic Approach to Multiple-Subject Diffusion MRI Tractography

DTIC Science & Technology

2010-04-01

distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT A global probabilistic fiber tracking approach based on the voting process provided by...umn.edu 2 ABSTRACT A global probabilistic fiber tracking approach based on the voting process provided by the Hough transform is introduced in...criteria for aligning curves and particularly tracts. In this work, we present a global probabilistic approach inspired by the voting procedure provided

Gadolinium chloride as a contrast agent for imaging wood composite components by magnetic resonance

Treesearch

Thomas L. Eberhardt; Chi-Leung So; Andrea Protti; Po-Wah So

2009-01-01

Although paramagnetic contrast agents have an established track record in medical uses of magnetic resonance imaging (MRI), only recently has a contrast agent been used for enhancing MRI images of solid wood specimens. Expanding on this concept, wood veneers were treated with a gadolinium-based contrast agent and used in a model system comprising three-ply plywood...

Dual-Tasking Alleviated Sleep Deprivation Disruption in Visuomotor Tracking: An fMRI Study

ERIC Educational Resources Information Center

Gazes, Yunglin; Rakitin, Brian C.; Steffener, Jason; Habeck, Christian; Butterfield, Brady; Basner, Robert C.; Ghez, Claude; Stern, Yaakov

2012-01-01

Effects of dual-responding on tracking performance after 49-h of sleep deprivation (SD) were evaluated behaviorally and with functional magnetic resonance imaging (fMRI). Continuous visuomotor tracking was performed simultaneously with an intermittent color-matching visual detection task in which a pair of color-matched stimuli constituted a…

Tissue-Point Motion Tracking in the Tongue from Cine MRI and Tagged MRI

ERIC Educational Resources Information Center

Woo, Jonghye; Stone, Maureen; Suo, Yuanming; Murano, Emi Z.; Prince, Jerry L.

2014-01-01

Purpose: Accurate tissue motion tracking within the tongue can help professionals diagnose and treat vocal tract--related disorders, evaluate speech quality before and after surgery, and conduct various scientific studies. The authors compared tissue tracking results from 4 widely used deformable registration (DR) methods applied to cine magnetic…

Manganese-impregnated mesoporous silica nanoparticles for signal enhancement in MRI cell labelling studies

NASA Astrophysics Data System (ADS)

Guillet-Nicolas, Rémy; Laprise-Pelletier, Myriam; Nair, Mahesh M.; Chevallier, Pascale; Lagueux, Jean; Gossuin, Yves; Laurent, Sophie; Kleitz, Freddy; Fortin, Marc-André

2013-11-01

Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn2+ is already implemented as a ``positive'' cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (~140 nm diam.) and high porosity (~60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(ii) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn2+ leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM-1 s-1 were measured at 60 MHz and 37 °C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because these Mn-labelled M48SNs express strong ``positive'' contrast media properties at low concentrations, they are potentially applicable for cell tracking and drug delivery methodologies.Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn2+ is already implemented as a ``positive'' cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (~140 nm diam.) and high porosity (~60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(ii) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn2+ leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM-1 s-1 were measured at 60 MHz and 37 °C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because these Mn-labelled M48SNs express strong ``positive'' contrast media properties at low concentrations, they are potentially applicable for cell tracking and drug delivery methodologies. Electronic supplementary information (ESI) available: TEM images, particle size distributions, XRD, TPR, magnetometric profiles, T1 and T2 measurements at 60 MHz over time, NMRD profiles of materials, P388 cell proliferation assay after 4 h and T1-w. MR images of P388 cells incubated with a solution of M48SNs. See DOI: 10.1039/c3nr02969g

Genes involved in prostate cancer progression determine MRI visibility

PubMed Central

Li, Ping; You, Sungyong; Nguyen, Christopher; Wang, Yanping; Kim, Jayoung; Sirohi, Deepika; Ziembiec, Asha; Luthringer, Daniel; Lin, Shih-Chieh; Daskivich, Timothy; Wu, Jonathan; Freeman, Michael R; Saouaf, Rola; Li, Debiao; Kim, Hyung L.

2018-01-01

MRI is used to image prostate cancer and target tumors for biopsy or therapeutic ablation. The objective was to understand the biology of tumors not visible on MRI that may go undiagnosed and untreated. Methods: Prostate cancers visible or invisible on multiparametric MRI were macrodissected and examined by RNAseq. Differentially expressed genes (DEGs) based on MRI visibility status were cross-referenced with publicly available gene expression databases to identify genes associated with disease progression. Genes with potential roles in determining MRI visibility and disease progression were knocked down in murine prostate cancer xenografts, and imaged by MRI. Results: RNAseq identified 1,654 DEGs based on MRI visibility status. Comparison of DEGs based on MRI visibility and tumor characteristics revealed that Gleason score (dissimilarity test, p<0.0001) and tumor size (dissimilarity test, p<0.039) did not completely determine MRI visibility. Genes in previously reported prognostic signatures significantly correlated with MRI visibility suggesting that MRI visibility was prognostic. Cross-referencing DEGs with external datasets identified four genes (PHYHD1, CENPF, ALDH2, GDF15) that predict MRI visibility, progression free survival and metastatic deposits. Genetic modification of a human prostate cancer cell line to induce miR-101 and suppress CENPF decreased cell migration and invasion. As prostate cancer xenografts in mice, these cells had decreased visibility on diffusion weighted MRI and decreased perfusion, which correlated with immunostaining showing decreased cell density and proliferation. Conclusions: Genes involved in prostate cancer prognosis and metastasis determine MRI visibility, indicating that MRI visibility has prognostic significance. MRI visibility was associated with genetic features linked to poor prognosis. PMID:29556354

Three-dimensional MRI-linac intra-fraction guidance using multiple orthogonal cine-MRI planes

NASA Astrophysics Data System (ADS)

Bjerre, Troels; Crijns, Sjoerd; Rosenschöld, Per Munck af; Aznar, Marianne; Specht, Lena; Larsen, Rasmus; Keall, Paul

2013-07-01

The introduction of integrated MRI-radiation therapy systems will offer live intra-fraction imaging. We propose a feasible low-latency multi-plane MRI-linac guidance strategy. In this work we demonstrate how interleaved acquired, orthogonal cine-MRI planes can be used for low-latency tracking of the 3D trajectory of a soft-tissue target structure. The proposed strategy relies on acquiring a pre-treatment 3D breath-hold scan, extracting a 3D target template and performing template matching between this 3D template and pairs of orthogonal 2D cine-MRI planes intersecting the target motion path. For a 60 s free-breathing series of orthogonal cine-MRI planes, we demonstrate that the method was capable of accurately tracking the respiration related 3D motion of the left kidney. Quantitative evaluation of the method using a dataset designed for this purpose revealed a translational error of 1.15 mm for a translation of 39.9 mm. We have demonstrated how interleaved acquired, orthogonal cine-MRI planes can be used for online tracking of soft-tissue target volumes.

Three-dimensional MRI-linac intra-fraction guidance using multiple orthogonal cine-MRI planes.

PubMed

Bjerre, Troels; Crijns, Sjoerd; af Rosenschöld, Per Munck; Aznar, Marianne; Specht, Lena; Larsen, Rasmus; Keall, Paul

2013-07-21

The introduction of integrated MRI-radiation therapy systems will offer live intra-fraction imaging. We propose a feasible low-latency multi-plane MRI-linac guidance strategy. In this work we demonstrate how interleaved acquired, orthogonal cine-MRI planes can be used for low-latency tracking of the 3D trajectory of a soft-tissue target structure. The proposed strategy relies on acquiring a pre-treatment 3D breath-hold scan, extracting a 3D target template and performing template matching between this 3D template and pairs of orthogonal 2D cine-MRI planes intersecting the target motion path. For a 60 s free-breathing series of orthogonal cine-MRI planes, we demonstrate that the method was capable of accurately tracking the respiration related 3D motion of the left kidney. Quantitative evaluation of the method using a dataset designed for this purpose revealed a translational error of 1.15 mm for a translation of 39.9 mm. We have demonstrated how interleaved acquired, orthogonal cine-MRI planes can be used for online tracking of soft-tissue target volumes.

Kalman filter-based EM-optical sensor fusion for needle deflection estimation.

PubMed

Jiang, Baichuan; Gao, Wenpeng; Kacher, Daniel; Nevo, Erez; Fetics, Barry; Lee, Thomas C; Jayender, Jagadeesan

2018-04-01

In many clinical procedures such as cryoablation that involves needle insertion, accurate placement of the needle's tip at the desired target is the major issue for optimizing the treatment and minimizing damage to the neighboring anatomy. However, due to the interaction force between the needle and tissue, considerable error in intraoperative tracking of the needle tip can be observed as needle deflects. In this paper, measurements data from an optical sensor at the needle base and a magnetic resonance (MR) gradient field-driven electromagnetic (EM) sensor placed 10 cm from the needle tip are used within a model-integrated Kalman filter-based sensor fusion scheme. Bending model-based estimations and EM-based direct estimation are used as the measurement vectors in the Kalman filter, thus establishing an online estimation approach. Static tip bending experiments show that the fusion method can reduce the mean error of the tip position estimation from 29.23 mm of the optical sensor-based approach to 3.15 mm of the fusion-based approach and from 39.96 to 6.90 mm, at the MRI isocenter and the MRI entrance, respectively. This work established a novel sensor fusion scheme that incorporates model information, which enables real-time tracking of needle deflection with MRI compatibility, in a free-hand operating setup.

MRI-assisted PET motion correction for neurologic studies in an integrated MR-PET scanner.

PubMed

Catana, Ciprian; Benner, Thomas; van der Kouwe, Andre; Byars, Larry; Hamm, Michael; Chonde, Daniel B; Michel, Christian J; El Fakhri, Georges; Schmand, Matthias; Sorensen, A Gregory

2011-01-01

Head motion is difficult to avoid in long PET studies, degrading the image quality and offsetting the benefit of using a high-resolution scanner. As a potential solution in an integrated MR-PET scanner, the simultaneously acquired MRI data can be used for motion tracking. In this work, a novel algorithm for data processing and rigid-body motion correction (MC) for the MRI-compatible BrainPET prototype scanner is described, and proof-of-principle phantom and human studies are presented. To account for motion, the PET prompt and random coincidences and sensitivity data for postnormalization were processed in the line-of-response (LOR) space according to the MRI-derived motion estimates. The processing time on the standard BrainPET workstation is approximately 16 s for each motion estimate. After rebinning in the sinogram space, the motion corrected data were summed, and the PET volume was reconstructed using the attenuation and scatter sinograms in the reference position. The accuracy of the MC algorithm was first tested using a Hoffman phantom. Next, human volunteer studies were performed, and motion estimates were obtained using 2 high-temporal-resolution MRI-based motion-tracking techniques. After accounting for the misalignment between the 2 scanners, perfectly coregistered MRI and PET volumes were reproducibly obtained. The MRI output gates inserted into the PET list-mode allow the temporal correlation of the 2 datasets within 0.2 ms. The Hoffman phantom volume reconstructed by processing the PET data in the LOR space was similar to the one obtained by processing the data using the standard methods and applying the MC in the image space, demonstrating the quantitative accuracy of the procedure. In human volunteer studies, motion estimates were obtained from echo planar imaging and cloverleaf navigator sequences every 3 s and 20 ms, respectively. Motion-deblurred PET images, with excellent delineation of specific brain structures, were obtained using these 2 MRI-based estimates. An MRI-based MC algorithm was implemented for an integrated MR-PET scanner. High-temporal-resolution MRI-derived motion estimates (obtained while simultaneously acquiring anatomic or functional MRI data) can be used for PET MC. An MRI-based MC method has the potential to improve PET image quality, increasing its reliability, reproducibility, and quantitative accuracy, and to benefit many neurologic applications.

4D tumor centroid tracking using orthogonal 2D dynamic MRI: Implications for radiotherapy planning

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

Tryggestad, Erik; Flammang, Aaron; Shea, Steven M.

2013-09-15

Purpose: Current pretreatment, 4D imaging techniques are suboptimal in that they sample breathing motion over a very limited “snapshot” in time. Heretofore, long-duration, 4D motion characterization for radiotherapy planning, margin optimization, and validation have been impractical for safety reasons, requiring invasive markers imaged under x-ray fluoroscopy. To characterize 3D tumor motion and associated variability over durations more consistent with treatments, the authors have developed a practical dynamic MRI (dMRI) technique employing two orthogonal planes acquired in a continuous, interleaved fashion.Methods: 2D balanced steady-state free precession MRI was acquired continuously over 9–14 min at approximately 4 Hz in three healthy volunteersmore » using a commercial 1.5 T system; alternating orthogonal imaging planes (sagittal, coronal, sagittal, etc.) were employed. The 2D in-plane pixel resolution was 2 × 2 mm{sup 2} with a 5 mm slice profile. Simultaneous with image acquisition, the authors monitored a 1D surrogate respiratory signal using a device available with the MRI system. 2D template matching-based anatomic feature registration, or tracking, was performed independently in each orientation. 4D feature tracking at the raw frame rate was derived using spline interpolation.Results: Tracking vascular features in the lung for two volunteers and pancreatic features in one volunteer, the authors have successfully demonstrated this method. Registration error, defined here as the difference between the sagittal and coronal tracking result in the SI direction, ranged from 0.7 to 1.6 mm (1σ) which was less than the acquired image resolution. Although the healthy volunteers were instructed to relax and breathe normally, significantly variable respiration was observed. To demonstrate potential applications of this technique, the authors subsequently explored the intrafraction stability of hypothetical tumoral internal target volumes and 3D spatial probability distribution functions. The surrogate respiratory information allowed the authors to show how this technique can be used to study correlations between internal and external (surrogate) information over these prolonged durations. However, compared against the gold standard of the time stamps in the dMRI frames, the temporal synchronization of the surrogate 1D respiratory information was shown to be likely unreliable.Conclusions: The authors have established viability of a novel and practical pretreatment, 4D tumor centroid tracking method employing a commercially available dynamic MRI sequence. Further developments from the vendor are likely needed to provide a reliably synchronized surrogate 1D respiratory signal, which will likely broaden the utility of this method in the pretreatment radiotherapy planning context.« less

MRI surveillance of cancer cell fate in a brain metastasis model after early radiotherapy.

PubMed

Murrell, Donna H; Zarghami, Niloufar; Jensen, Michael D; Dickson, Fiona; Chambers, Ann F; Wong, Eugene; Foster, Paula J

2017-10-01

Incidence of brain metastasis attributed to breast cancer is increasing and prognosis is poor. It is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatments, thereby facilitating a mechanism for recurrence. Radiotherapy is used to treat brain metastases clinically, but assessment has been limited to macroscopic tumor volumes detectable by clinical imaging. Here, we use cellular MRI to understand the concurrent responses of metastases and nonproliferative or slowly cycling cancer cells to radiotherapy. MRI cell tracking was used to investigate the impact of early cranial irradiation on the fate of individual iron-labeled cancer cells and outgrowth of breast cancer brain metastases in the human MDA-MB-231-BR-HER2 cell model. Early whole-brain radiotherapy significantly reduced the outgrowth of metastases from individual disseminated cancer cells in treated animals compared to controls. However, the numbers of nonproliferative iron-retaining cancer cells in the brain were not significantly different. Radiotherapy, when given early in cancer progression, is effective in preventing the outgrowth of solitary cancer cells to brain metastases. Future studies of the nonproliferative cancer cells' clonogenic potentials are warranted, given that their persistent presence suggests that they may have evaded treatment. Magn Reson Med 78:1506-1512, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Implicit sequence-specific motor learning after sub-cortical stroke is associated with increased prefrontal brain activations: An fMRI study

PubMed Central

Meehan, Sean K.; Randhawa, Bubblepreet; Wessel, Brenda; Boyd, Lara A.

2010-01-01

Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and 9 individuals with chronic, right focal sub-cortical stroke performed a continuous joystick-based tracking task during an initial fMRI session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequences during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased BOLD response in left dorsal premotor cortex (BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. The present study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke. PMID:20725908

Cellular transfer of magnetic nanoparticles via cell microvesicles: impact on cell tracking by magnetic resonance imaging.

PubMed

Silva, Amanda K Andriola; Wilhelm, Claire; Kolosnjaj-Tabi, Jelena; Luciani, Nathalie; Gazeau, Florence

2012-05-01

Cell labeling with magnetic nanoparticles can be used to monitor the fate of transplanted cells in vivo by magnetic resonance imaging. However, nanoparticles initially internalized in administered cells might end up in other cells of the host organism. We investigated a mechanism of intercellular cross-transfer of magnetic nanoparticles to different types of recipient cells via cell microvesicles released under cellular stress. Three cell types (mesenchymal stem cells, endothelial cells and macrophages) were labeled with 8-nm iron oxide nanoparticles. Then cells underwent starvation stress, during which they produced microvesicles that were subsequently transferred to unlabeled recipient cells. The analysis of the magnetophoretic mobility of donor cells indicated that magnetic load was partially lost under cell stress. Microvesicles shed by stressed cells participated in the release of magnetic label. Moreover, such microvesicles were uptaken by naïve cells, resulting in cellular redistribution of nanoparticles. Iron load of recipient cells allowed their detection by MRI. Cell microvesicles released under stress may be disseminated throughout the organism, where they can be uptaken by host cells. The transferred cargo may be sufficient to allow MRI detection of these secondarily labeled cells, leading to misinterpretations of the effectiveness of transplanted cells.

Design and preliminary accuracy studies of an MRI-guided transrectal prostate intervention system.

PubMed

Krieger, Axel; Csoma, Csaba; Iordachital, Iulian I; Guion, Peter; Singh, Anurag K; Fichtinger, Gabor; Whitcomb, Louis L

2007-01-01

This paper reports a novel system for magnetic resonance imaging (MRI) guided transrectal prostate interventions, such as needle biopsy, fiducial marker placement, and therapy delivery. The system utilizes a hybrid tracking method, comprised of passive fiducial tracking for initial registration and subsequent incremental motion measurement along the degrees of freedom using fiber-optical encoders and mechanical scales. Targeting accuracy of the system is evaluated in prostate phantom experiments. Achieved targeting accuracy and procedure times were found to compare favorably with existing systems using passive and active tracking methods. Moreover, the portable design of the system using only standard MRI image sequences and minimal custom scanner interfacing allows the system to be easily used on different MRI scanners.

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

PubMed

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

2017-06-01

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

Framework for 2D-3D image fusion of infrared thermography with preoperative MRI.

PubMed

Hoffmann, Nico; Weidner, Florian; Urban, Peter; Meyer, Tobias; Schnabel, Christian; Radev, Yordan; Schackert, Gabriele; Petersohn, Uwe; Koch, Edmund; Gumhold, Stefan; Steiner, Gerald; Kirsch, Matthias

2017-11-27

Multimodal medical image fusion combines information of one or more images in order to improve the diagnostic value. While previous applications mainly focus on merging images from computed tomography, magnetic resonance imaging (MRI), ultrasonic and single-photon emission computed tomography, we propose a novel approach for the registration and fusion of preoperative 3D MRI with intraoperative 2D infrared thermography. Image-guided neurosurgeries are based on neuronavigation systems, which further allow us track the position and orientation of arbitrary cameras. Hereby, we are able to relate the 2D coordinate system of the infrared camera with the 3D MRI coordinate system. The registered image data are now combined by calibration-based image fusion in order to map our intraoperative 2D thermographic images onto the respective brain surface recovered from preoperative MRI. In extensive accuracy measurements, we found that the proposed framework achieves a mean accuracy of 2.46 mm.

Evaluation of an active magnetic resonance tracking system for interstitial brachytherapy.

PubMed

Wang, Wei; Viswanathan, Akila N; Damato, Antonio L; Chen, Yue; Tse, Zion; Pan, Li; Tokuda, Junichi; Seethamraju, Ravi T; Dumoulin, Charles L; Schmidt, Ehud J; Cormack, Robert A

2015-12-01

In gynecologic cancers, magnetic resonance (MR) imaging is the modality of choice for visualizing tumors and their surroundings because of superior soft-tissue contrast. Real-time MR guidance of catheter placement in interstitial brachytherapy facilitates target coverage, and would be further improved by providing intraprocedural estimates of dosimetric coverage. A major obstacle to intraprocedural dosimetry is the time needed for catheter trajectory reconstruction. Herein the authors evaluate an active MR tracking (MRTR) system which provides rapid catheter tip localization and trajectory reconstruction. The authors assess the reliability and spatial accuracy of the MRTR system in comparison to standard catheter digitization using magnetic resonance imaging (MRI) and CT. The MRTR system includes a stylet with microcoils mounted on its shaft, which can be inserted into brachytherapy catheters and tracked by a dedicated MRTR sequence. Catheter tip localization errors of the MRTR system and their dependence on catheter locations and orientation inside the MR scanner were quantified with a water phantom. The distances between the tracked tip positions of the MRTR stylet and the predefined ground-truth tip positions were calculated for measurements performed at seven locations and with nine orientations. To evaluate catheter trajectory reconstruction, fifteen brachytherapy catheters were placed into a gel phantom with an embedded catheter fixation framework, with parallel or crossed paths. The MRTR stylet was then inserted sequentially into each catheter. During the removal of the MRTR stylet from within each catheter, a MRTR measurement was performed at 40 Hz to acquire the instantaneous stylet tip position, resulting in a series of three-dimensional (3D) positions along the catheter's trajectory. A 3D polynomial curve was fit to the tracked positions for each catheter, and equally spaced dwell points were then generated along the curve. High-resolution 3D MRI of the phantom was performed followed by catheter digitization based on the catheter's imaging artifacts. The catheter trajectory error was characterized in terms of the mean distance between corresponding dwell points in MRTR-generated catheter trajectory and MRI-based catheter digitization. The MRTR-based catheter trajectory reconstruction process was also performed on three gynecologic cancer patients, and then compared with catheter digitization based on MRI and CT. The catheter tip localization error increased as the MRTR stylet moved further off-center and as the stylet's orientation deviated from the main magnetic field direction. Fifteen catheters' trajectories were reconstructed by MRTR. Compared with MRI-based digitization, the mean 3D error of MRTR-generated trajectories was 1.5 ± 0.5 mm with an in-plane error of 0.7 ± 0.2 mm and a tip error of 1.7 ± 0.5 mm. MRTR resolved ambiguity in catheter assignment due to crossed catheter paths, which is a common problem in image-based catheter digitization. In the patient studies, the MRTR-generated catheter trajectory was consistent with digitization based on both MRI and CT. The MRTR system provides accurate catheter tip localization and trajectory reconstruction in the MR environment. Relative to the image-based methods, it improves the speed, safety, and reliability of the catheter trajectory reconstruction in interstitial brachytherapy. MRTR may enable in-procedural dosimetric evaluation of implant target coverage.

Evaluation of an active magnetic resonance tracking system for interstitial brachytherapy

PubMed Central

Wang, Wei; Viswanathan, Akila N.; Damato, Antonio L.; Chen, Yue; Tse, Zion; Pan, Li; Tokuda, Junichi; Seethamraju, Ravi T.; Dumoulin, Charles L.; Schmidt, Ehud J.; Cormack, Robert A.

2015-01-01

Purpose: In gynecologic cancers, magnetic resonance (MR) imaging is the modality of choice for visualizing tumors and their surroundings because of superior soft-tissue contrast. Real-time MR guidance of catheter placement in interstitial brachytherapy facilitates target coverage, and would be further improved by providing intraprocedural estimates of dosimetric coverage. A major obstacle to intraprocedural dosimetry is the time needed for catheter trajectory reconstruction. Herein the authors evaluate an active MR tracking (MRTR) system which provides rapid catheter tip localization and trajectory reconstruction. The authors assess the reliability and spatial accuracy of the MRTR system in comparison to standard catheter digitization using magnetic resonance imaging (MRI) and CT. Methods: The MRTR system includes a stylet with microcoils mounted on its shaft, which can be inserted into brachytherapy catheters and tracked by a dedicated MRTR sequence. Catheter tip localization errors of the MRTR system and their dependence on catheter locations and orientation inside the MR scanner were quantified with a water phantom. The distances between the tracked tip positions of the MRTR stylet and the predefined ground-truth tip positions were calculated for measurements performed at seven locations and with nine orientations. To evaluate catheter trajectory reconstruction, fifteen brachytherapy catheters were placed into a gel phantom with an embedded catheter fixation framework, with parallel or crossed paths. The MRTR stylet was then inserted sequentially into each catheter. During the removal of the MRTR stylet from within each catheter, a MRTR measurement was performed at 40 Hz to acquire the instantaneous stylet tip position, resulting in a series of three-dimensional (3D) positions along the catheter’s trajectory. A 3D polynomial curve was fit to the tracked positions for each catheter, and equally spaced dwell points were then generated along the curve. High-resolution 3D MRI of the phantom was performed followed by catheter digitization based on the catheter’s imaging artifacts. The catheter trajectory error was characterized in terms of the mean distance between corresponding dwell points in MRTR-generated catheter trajectory and MRI-based catheter digitization. The MRTR-based catheter trajectory reconstruction process was also performed on three gynecologic cancer patients, and then compared with catheter digitization based on MRI and CT. Results: The catheter tip localization error increased as the MRTR stylet moved further off-center and as the stylet’s orientation deviated from the main magnetic field direction. Fifteen catheters’ trajectories were reconstructed by MRTR. Compared with MRI-based digitization, the mean 3D error of MRTR-generated trajectories was 1.5 ± 0.5 mm with an in-plane error of 0.7 ± 0.2 mm and a tip error of 1.7 ± 0.5 mm. MRTR resolved ambiguity in catheter assignment due to crossed catheter paths, which is a common problem in image-based catheter digitization. In the patient studies, the MRTR-generated catheter trajectory was consistent with digitization based on both MRI and CT. Conclusions: The MRTR system provides accurate catheter tip localization and trajectory reconstruction in the MR environment. Relative to the image-based methods, it improves the speed, safety, and reliability of the catheter trajectory reconstruction in interstitial brachytherapy. MRTR may enable in-procedural dosimetric evaluation of implant target coverage. PMID:26632065

Evaluation of an active magnetic resonance tracking system for interstitial brachytherapy

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

Wang, Wei, E-mail: wwang21@partners.org; Viswanathan, Akila N.; Damato, Antonio L.

2015-12-15

Purpose: In gynecologic cancers, magnetic resonance (MR) imaging is the modality of choice for visualizing tumors and their surroundings because of superior soft-tissue contrast. Real-time MR guidance of catheter placement in interstitial brachytherapy facilitates target coverage, and would be further improved by providing intraprocedural estimates of dosimetric coverage. A major obstacle to intraprocedural dosimetry is the time needed for catheter trajectory reconstruction. Herein the authors evaluate an active MR tracking (MRTR) system which provides rapid catheter tip localization and trajectory reconstruction. The authors assess the reliability and spatial accuracy of the MRTR system in comparison to standard catheter digitization usingmore » magnetic resonance imaging (MRI) and CT. Methods: The MRTR system includes a stylet with microcoils mounted on its shaft, which can be inserted into brachytherapy catheters and tracked by a dedicated MRTR sequence. Catheter tip localization errors of the MRTR system and their dependence on catheter locations and orientation inside the MR scanner were quantified with a water phantom. The distances between the tracked tip positions of the MRTR stylet and the predefined ground-truth tip positions were calculated for measurements performed at seven locations and with nine orientations. To evaluate catheter trajectory reconstruction, fifteen brachytherapy catheters were placed into a gel phantom with an embedded catheter fixation framework, with parallel or crossed paths. The MRTR stylet was then inserted sequentially into each catheter. During the removal of the MRTR stylet from within each catheter, a MRTR measurement was performed at 40 Hz to acquire the instantaneous stylet tip position, resulting in a series of three-dimensional (3D) positions along the catheter’s trajectory. A 3D polynomial curve was fit to the tracked positions for each catheter, and equally spaced dwell points were then generated along the curve. High-resolution 3D MRI of the phantom was performed followed by catheter digitization based on the catheter’s imaging artifacts. The catheter trajectory error was characterized in terms of the mean distance between corresponding dwell points in MRTR-generated catheter trajectory and MRI-based catheter digitization. The MRTR-based catheter trajectory reconstruction process was also performed on three gynecologic cancer patients, and then compared with catheter digitization based on MRI and CT. Results: The catheter tip localization error increased as the MRTR stylet moved further off-center and as the stylet’s orientation deviated from the main magnetic field direction. Fifteen catheters’ trajectories were reconstructed by MRTR. Compared with MRI-based digitization, the mean 3D error of MRTR-generated trajectories was 1.5 ± 0.5 mm with an in-plane error of 0.7 ± 0.2 mm and a tip error of 1.7 ± 0.5 mm. MRTR resolved ambiguity in catheter assignment due to crossed catheter paths, which is a common problem in image-based catheter digitization. In the patient studies, the MRTR-generated catheter trajectory was consistent with digitization based on both MRI and CT. Conclusions: The MRTR system provides accurate catheter tip localization and trajectory reconstruction in the MR environment. Relative to the image-based methods, it improves the speed, safety, and reliability of the catheter trajectory reconstruction in interstitial brachytherapy. MRTR may enable in-procedural dosimetric evaluation of implant target coverage.« less

Tracking Normalization of Brain Tumor Vasculature by Magnetic Imaging and Proangiogenic Biomarkers

PubMed Central

Hormigo, Adília; Gutin, Philip H.; Rafii, Shahin

2010-01-01

Clinical assessment of the response to antiangiogenic therapy has been cumbersome. A study in this issue of Cancer Cell demonstrates that a combination of magnetic resonance imaging (MRI) for quantification of normalized vessels with measurements of circulating levels of proangiogenic factors, including FGF2, SDF1, and viable circulating endothelial cells, provides an effective means to evaluate the response of recurrent glioblastoma to a prototypical pan-VEGF receptor tyrosine kinase inhibitor, AZD2171. PMID:17222788

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence

PubMed Central

Ribot, Emeline J; Gaudet, Jeffrey M; Chen, Yuhua; Gilbert, Kyle M; Foster, Paula J

2014-01-01

Mesenchymal stem cells (MSC) are used to restore deteriorated cell environments. There is a need to specifically track these cells following transplantation in order to evaluate different methods of implantation, to follow their migration within the body, and to quantify their accumulation at the target. Cellular magnetic resonance imaging (MRI) using fluorine-based nanoemulsions is a great means to detect these transplanted cells in vivo because of the high specificity for fluorine detection and the capability for precise quantification. This technique, however, has low sensitivity, necessitating improvement in MR sequences. To counteract this issue, the balanced steady-state free precession (bSSFP) imaging sequence can be of great interest due to the high signal-to-noise ratio (SNR). Furthermore, it can be applied to obtain 3D images within short acquisition times. In this paper, bSSFP provided accurate quantification of samples of the perfluorocarbon Cell Sense-labeled cells in vitro. Cell Sense was internalized by human MSC (hMSC) without adverse alterations in cell viability or differentiation into adipocytes/osteocytes. The bSSFP sequence was applied in vivo to track and quantify the signals from both Cell Sense-labeled and iron-labeled hMSC after intramuscular implantation. The fluorine signal was observed to decrease faster and more significantly than the volume of iron-associated voids, which points to the advantage of quantifying the fluorine signal and the complexity of quantifying signal loss due to iron. PMID:24748787

In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence.

PubMed

Ribot, Emeline J; Gaudet, Jeffrey M; Chen, Yuhua; Gilbert, Kyle M; Foster, Paula J

2014-01-01

Mesenchymal stem cells (MSC) are used to restore deteriorated cell environments. There is a need to specifically track these cells following transplantation in order to evaluate different methods of implantation, to follow their migration within the body, and to quantify their accumulation at the target. Cellular magnetic resonance imaging (MRI) using fluorine-based nanoemulsions is a great means to detect these transplanted cells in vivo because of the high specificity for fluorine detection and the capability for precise quantification. This technique, however, has low sensitivity, necessitating improvement in MR sequences. To counteract this issue, the balanced steady-state free precession (bSSFP) imaging sequence can be of great interest due to the high signal-to-noise ratio (SNR). Furthermore, it can be applied to obtain 3D images within short acquisition times. In this paper, bSSFP provided accurate quantification of samples of the perfluorocarbon Cell Sense-labeled cells in vitro. Cell Sense was internalized by human MSC (hMSC) without adverse alterations in cell viability or differentiation into adipocytes/osteocytes. The bSSFP sequence was applied in vivo to track and quantify the signals from both Cell Sense-labeled and iron-labeled hMSC after intramuscular implantation. The fluorine signal was observed to decrease faster and more significantly than the volume of iron-associated voids, which points to the advantage of quantifying the fluorine signal and the complexity of quantifying signal loss due to iron.

Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal 19 F MRI Agents.

PubMed

Kirberger, Steven E; Maltseva, Sofia D; Manulik, Joseph C; Einstein, Samuel A; Weegman, Bradley P; Garwood, Michael; Pomerantz, William C K

2017-06-01

19 F MRI is valuable for in vivo imaging due to the only trace amounts of fluorine in biological systems. Because of the low sensitivity of MRI however, designing new fluorochemicals remains a significant challenge for achieving sufficient 19 F signal. Here, we describe a new class of high-signal, water-soluble fluorochemicals as 19 F MRI imaging agents. A polyamide backbone is used for tuning the proteolytic stability to avoid retention within the body, which is a limitation of current state-of-the-art perfluorochemicals. We show that unstructured peptides containing alternating N-ϵ-trifluoroacetyllysine and lysine provide a degenerate 19 F NMR signal. 19 F MRI phantom images provide sufficient contrast at micromolar concentrations, showing promise for eventual clinical applications. Finally, the degenerate high signal characteristics were retained when conjugated to a large protein, indicating potential for in vivo targeting applications, including molecular imaging and cell tracking. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gold and Iron-Gold Nanoparticles for Intracellular Tracking and in Vivo Medical Applicatons

NASA Astrophysics Data System (ADS)

Fu, Wei

2005-03-01

We have fabricated Au and Fe-Au nanoparticles for potential use in ex vivo experiments such as intracellular tracking, as well as a variety of in vivo medical applications. In order to improve their targeting potential, circulation time and flexibility, gold NPs were surface modified using a hetero-bifunctional poly(ethylene glycol) (PEG, MW 1,500) spacers. A coumarin-PEG-gold NP complex was formed and cell viability studies and optical fluorescence experiments were carried out demonstrating the use of these surface-modified gold NPs for drug delivery, gene therapy and cell trafficking experiments. Fe-Au nanoparticles were also fabricated and show significant contrast enhancement in MRI studies through a substantial reduction of the T2 relaxation time.

Real Time Target Tracking in a Phantom Using Ultrasonic Imaging

NASA Astrophysics Data System (ADS)

Xiao, X.; Corner, G.; Huang, Z.

In this paper we present a real-time ultrasound image guidance method suitable for tracking the motion of tumors. A 2D ultrasound based motion tracking system was evaluated. A robot was used to control the focused ultrasound and position it at the target that has been segmented from a real-time ultrasound video. Tracking accuracy and precision were investigated using a lesion mimicking phantom. Experiments have been conducted and results show sufficient efficiency of the image guidance algorithm. This work could be developed as the foundation for combining the real time ultrasound imaging tracking and MRI thermometry monitoring non-invasive surgery.

Engineered core-shell magnetic nanoparticle for MR dual-modal tracking and safe magnetic manipulation of ependymal cells in live rodents

NASA Astrophysics Data System (ADS)

Peng, Yung-Kang; Lui, Cathy N. P.; Chen, Yu-Wei; Chou, Shang-Wei; Chou, Pi-Tai; Yung, Ken K. L.; Edman Tsang, S. C.

2018-01-01

Tagging recognition group(s) on superparamagnetic iron oxide is known to aid localisation (imaging), stimulation and separation of biological entities using magnetic resonance imaging (MRI) and magnetic agitation/separation (MAS) techniques. Despite the wide applicability of iron oxide nanoparticles in T 2-weighted MRI and MAS, the quality of the images and safe manipulation of the exceptionally delicate neural cells in a live brain are currently the key challenges. Here, we demonstrate the engineered manganese oxide clusters-iron oxide core-shell nanoparticle as an MR dual-modal contrast agent for neural stem cells (NSCs) imaging and magnetic manipulation in live rodents. As a result, using this engineered nanoparticle and associated technologies, identification, stimulation and transportation of labelled potentially multipotent NSCs from a specific location of a live brain to another by magnetic means for self-healing therapy can therefore be made possible.

Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation

PubMed Central

Gustafsson, Björn; Youens, Susan; Louie, Angelique Y.

2008-01-01

Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the sub-clinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI. PMID:16536488

Labeling of stem cells with monocrystalline iron oxide for tracking and localization by magnetic resonance imaging

PubMed Central

Calzi, Sergio Li; Kent, David L.; Chang, Kyung-Hee; Padgett, Kyle R.; Afzal, Aqeela; Chandra, Saurav B.; Caballero, Sergio; English, Denis; Garlington, Wendy; Hiscott, Paul S.; Sheridan, Carl M.; Grant, Maria B.; Forder, John R.

2013-01-01

Precise localization of exogenously delivered stem cells is critical to our understanding of their reparative response. Our current inability to determine the exact location of small numbers of cells may hinder optimal development of these cells for clinical use. We describe a method using magnetic resonance imaging to track and localize small numbers of stem cells following transplantation. Endothelial progenitor cells (EPC) were labeled with monocrystalline iron oxide nanoparticles (MIONs) which neither adversely altered their viability nor their ability to migrate in vitro and allowed successful detection of limited numbers of these cells in muscle. MION-labeled stem cells were also injected into the vitreous cavity of mice undergoing the model of choroidal neovascularization, laser rupture of Bruch’s membrane. Migration of the MION-labeled cells from the injection site towards the laser burns was visualized by MRI. In conclusion, MION labeling of EPC provides a non-invasive means to define the location of small numbers of these cells. Localization of these cells following injection is critical to their optimization for therapy. PMID:19345699

Surface-Based fMRI-Driven Diffusion Tractography in the Presence of Significant Brain Pathology: A Study Linking Structure and Function in Cerebral Palsy

PubMed Central

Cunnington, Ross; Boyd, Roslyn N.; Rose, Stephen E.

2016-01-01

Diffusion MRI (dMRI) tractography analyses are difficult to perform in the presence of brain pathology. Automated methods that rely on cortical parcellation for structural connectivity studies often fail, while manually defining regions is extremely time consuming and can introduce human error. Both methods also make assumptions about structure-function relationships that may not hold after cortical reorganisation. Seeding tractography with functional-MRI (fMRI) activation is an emerging method that reduces these confounds, but inherent smoothing of fMRI signal may result in the inclusion of irrelevant pathways. This paper describes a novel fMRI-seeded dMRI-analysis pipeline based on surface-meshes that reduces these issues and utilises machine-learning to generate task specific white matter pathways, minimising the requirement for manually-drawn ROIs. We directly compared this new strategy to a standard voxelwise fMRI-dMRI approach, by investigating correlations between clinical scores and dMRI metrics of thalamocortical and corticomotor tracts in 31 children with unilateral cerebral palsy. The surface-based approach successfully processed more participants (87%) than the voxel-based approach (65%), and provided significantly more-coherent tractography. Significant correlations between dMRI metrics and five clinical scores of function were found for the more superior regions of these tracts. These significant correlations were stronger and more frequently found with the surface-based method (15/20 investigated were significant; R2 = 0.43–0.73) than the voxelwise analysis (2 sig. correlations; 0.38 & 0.49). More restricted fMRI signal, better-constrained tractography, and the novel track-classification method all appeared to contribute toward these differences. PMID:27487011

Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions--a pilot study.

PubMed

Geburek, Florian; Mundle, Kathrin; Conrad, Sabine; Hellige, Maren; Walliser, Ulrich; van Schie, Hans T M; van Weeren, René; Skutella, Thomas; Stadler, Peter M

2016-02-01

Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of this study was to monitor the presence of intralesionally injected autologous AT-MSCs labelled with superparamagnetic iron oxide (SPIO) nanoparticles and green fluorescent protein (GFP) over a staggered period of 3 to 9 weeks with standing magnetic resonance imaging (MRI) and histology. Four adult warmblood horses received a unilateral injection of 10 × 10(6) autologous AT-MSCs into surgically created front-limb SDFT lesions. Administered AT-MSCs expressed lentivirally transduced reporter genes for GFP and were co-labelled with SPIO particles in three horses. The presence of AT-MSCs in SDFTs was evaluated by repeated examinations with standing low-field MRI in two horses and post-mortem in all horses with Prussian blue staining, fluorescence microscopy and with immunofluorescence and immunohistochemistry using anti-GFP antibodies at 3, 5, 7 and 9 weeks after treatment. AT-MSCs labelled with SPIO particles were detectable in treated SDFTs during each MRI in T2*- and T1-weighted sequences until the end of the observation period. Post-mortem examinations revealed that all treated tendons contained high numbers of SPIO- and GFP-labelled cells. Standing low-field MRI has the potential to track SPIO-labelled AT-MSCs successfully. Histology, fluorescence microscopy, immunofluorescence and immunohistochemistry are efficient tools to detect labelled AT-MSCs after intralesional injection into surgically created equine SDFT lesions. Intralesional injection of 10 × 10(6) AT-MSCs leads to the presence of high numbers of AT-MSCs in and around surgically created tendon lesions for up to 9 weeks. Integration of injected AT-MSCs into healing tendon tissue is an essential pathway after intralesional administration. Injection techniques have to be chosen deliberately to avoid reflux of the cell substrate injected. In vivo low-field MRI may be used as a non-invasive tool to monitor homing and engraftment of AT-MSCs in horses with tendinopathy of the SDFT.

Target motion tracking in MRI-guided transrectal robotic prostate biopsy.

PubMed

Tadayyon, Hadi; Lasso, Andras; Kaushal, Aradhana; Guion, Peter; Fichtinger, Gabor

2011-11-01

MRI-guided prostate needle biopsy requires compensation for organ motion between target planning and needle placement. Two questions are studied and answered in this paper: 1) is rigid registration sufficient in tracking the targets with an error smaller than the clinically significant size of prostate cancer and 2) what is the effect of the number of intraoperative slices on registration accuracy and speed? we propose multislice-to-volume registration algorithms for tracking the biopsy targets within the prostate. Three orthogonal plus additional transverse intraoperative slices are acquired in the approximate center of the prostate and registered with a high-resolution target planning volume. Both rigid and deformable scenarios were implemented. Both simulated and clinical MRI-guided robotic prostate biopsy data were used to assess tracking accuracy. average registration errors in clinical patient data were 2.6 mm for the rigid algorithm and 2.1 mm for the deformable algorithm. rigid tracking appears to be promising. Three tracking slices yield significantly high registration speed with an affordable error.

Magnetic resonance imaging of single co-labeled mesenchymal stromal cells after intracardial injection in mice.

PubMed

Salamon, J; Wicklein, D; Didié, M; Lange, C; Schumacher, U; Adam, G; Peldschus, K

2014-04-01

The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0 T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids in the kidneys. In the brain, an average of 4.6 ± 1.2 (n1), 9.0 ± 3.6 (n2) and 25.0 ± 1.0 (n3) signal voids were detected per MRI slice. An average of 8.7 ± 3.1 (n1), 22.0 ± 6.1 (n2) and 89.8 ± 6.5 (n3) labeled cells per corresponding stack of adjacent cryosections could be detected in the brain. Statistical correlation of the numbers of MRI signal voids in the brain and single MSC found by histology revealed a correlation coefficient of r = 0.91. The study demonstrates efficient magnetic and fluorescent co-labeling of MSC and their detection on a single cell level in mice by in-vivo MRI and histology. The described techniques may broaden the methods for in-vivo tracking of MSC. • Detection of single magnetically labeled MSC in-vivo using a clinical 3.0 T MRI is possible.• Fluorescent and magnetic co-labeling does not affect cell vitality.• The number of cells detected by MRI and histology has a high correlation. © Georg Thieme Verlag KG Stuttgart · New York.

Intra-operative prostate motion tracking using surface markers for robot-assisted laparoscopic radical prostatectomy

NASA Astrophysics Data System (ADS)

Esteghamatian, Mehdi; Sarkar, Kripasindhu; Pautler, Stephen E.; Chen, Elvis C. S.; Peters, Terry M.

2012-02-01

Radical prostatectomy surgery (RP) is the gold standard for treatment of localized prostate cancer (PCa). Recently, emergence of minimally invasive techniques such as Laparoscopic Radical Prostatectomy (LRP) and Robot-Assisted Laparoscopic Radical Prostatectomy (RARP) has improved the outcomes for prostatectomy. However, it remains difficult for the surgeons to make informed decisions regarding resection margins and nerve sparing since the location of the tumor within the organ is not usually visible in a laparoscopic view. While MRI enables visualization of the salient structures and cancer foci, its efficacy in LRP is reduced unless it is fused into a stereoscopic view such that homologous structures overlap. Registration of the MRI image and peri-operative ultrasound image using a tracked probe can potentially be exploited to bring the pre-operative information into alignment with the patient coordinate system during the procedure. While doing so, prostate motion needs to be compensated in real-time to synchronize the stereoscopic view with the pre-operative MRI during the prostatectomy procedure. In this study, a point-based stereoscopic tracking technique is investigated to compensate for rigid prostate motion so that the same motion can be applied to the pre-operative images. This method benefits from stereoscopic tracking of the surface markers implanted over the surface of the prostate phantom. The average target registration error using this approach was 3.25+/-1.43mm.

An integrated model-driven method for in-treatment upper airway motion tracking using cine MRI in head and neck radiation therapy

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

Li, Hua, E-mail: huli@radonc.wustl.edu; Chen, Hsin

Purpose: For the first time, MRI-guided radiation therapy systems can acquire cine images to dynamically monitor in-treatment internal organ motion. However, the complex head and neck (H&N) structures and low-contrast/resolution of on-board cine MRI images make automatic motion tracking a very challenging task. In this study, the authors proposed an integrated model-driven method to automatically track the in-treatment motion of the H&N upper airway, a complex and highly deformable region wherein internal motion often occurs in an either voluntary or involuntary manner, from cine MRI images for the analysis of H&N motion patterns. Methods: Considering the complex H&N structures andmore » ensuring automatic and robust upper airway motion tracking, the authors firstly built a set of linked statistical shapes (including face, face-jaw, and face-jaw-palate) using principal component analysis from clinically approved contours delineated on a set of training data. The linked statistical shapes integrate explicit landmarks and implicit shape representation. Then, a hierarchical model-fitting algorithm was developed to align the linked shapes on the first image frame of a to-be-tracked cine sequence and to localize the upper airway region. Finally, a multifeature level set contour propagation scheme was performed to identify the upper airway shape change, frame-by-frame, on the entire image sequence. The multifeature fitting energy, including the information of intensity variations, edge saliency, curve geometry, and temporal shape continuity, was minimized to capture the details of moving airway boundaries. Sagittal cine MR image sequences acquired from three H&N cancer patients were utilized to demonstrate the performance of the proposed motion tracking method. Results: The tracking accuracy was validated by comparing the results to the average of two manual delineations in 50 randomly selected cine image frames from each patient. The resulting average dice similarity coefficient (93.28%  ±  1.46%) and margin error (0.49  ±  0.12 mm) showed good agreement between the automatic and manual results. The comparison with three other deformable model-based segmentation methods illustrated the superior shape tracking performance of the proposed method. Large interpatient variations of swallowing frequency, swallowing duration, and upper airway cross-sectional area were observed from the testing cine image sequences. Conclusions: The proposed motion tracking method can provide accurate upper airway motion tracking results, and enable automatic and quantitative identification and analysis of in-treatment H&N upper airway motion. By integrating explicit and implicit linked-shape representations within a hierarchical model-fitting process, the proposed tracking method can process complex H&N structures and low-contrast/resolution cine MRI images. Future research will focus on the improvement of method reliability, patient motion pattern analysis for providing more information on patient-specific prediction of structure displacements, and motion effects on dosimetry for better H&N motion management in radiation therapy.« less

An integrated model-driven method for in-treatment upper airway motion tracking using cine MRI in head and neck radiation therapy.

PubMed

Li, Hua; Chen, Hsin-Chen; Dolly, Steven; Li, Harold; Fischer-Valuck, Benjamin; Victoria, James; Dempsey, James; Ruan, Su; Anastasio, Mark; Mazur, Thomas; Gach, Michael; Kashani, Rojano; Green, Olga; Rodriguez, Vivian; Gay, Hiram; Thorstad, Wade; Mutic, Sasa

2016-08-01

For the first time, MRI-guided radiation therapy systems can acquire cine images to dynamically monitor in-treatment internal organ motion. However, the complex head and neck (H&N) structures and low-contrast/resolution of on-board cine MRI images make automatic motion tracking a very challenging task. In this study, the authors proposed an integrated model-driven method to automatically track the in-treatment motion of the H&N upper airway, a complex and highly deformable region wherein internal motion often occurs in an either voluntary or involuntary manner, from cine MRI images for the analysis of H&N motion patterns. Considering the complex H&N structures and ensuring automatic and robust upper airway motion tracking, the authors firstly built a set of linked statistical shapes (including face, face-jaw, and face-jaw-palate) using principal component analysis from clinically approved contours delineated on a set of training data. The linked statistical shapes integrate explicit landmarks and implicit shape representation. Then, a hierarchical model-fitting algorithm was developed to align the linked shapes on the first image frame of a to-be-tracked cine sequence and to localize the upper airway region. Finally, a multifeature level set contour propagation scheme was performed to identify the upper airway shape change, frame-by-frame, on the entire image sequence. The multifeature fitting energy, including the information of intensity variations, edge saliency, curve geometry, and temporal shape continuity, was minimized to capture the details of moving airway boundaries. Sagittal cine MR image sequences acquired from three H&N cancer patients were utilized to demonstrate the performance of the proposed motion tracking method. The tracking accuracy was validated by comparing the results to the average of two manual delineations in 50 randomly selected cine image frames from each patient. The resulting average dice similarity coefficient (93.28%  ±  1.46%) and margin error (0.49  ±  0.12 mm) showed good agreement between the automatic and manual results. The comparison with three other deformable model-based segmentation methods illustrated the superior shape tracking performance of the proposed method. Large interpatient variations of swallowing frequency, swallowing duration, and upper airway cross-sectional area were observed from the testing cine image sequences. The proposed motion tracking method can provide accurate upper airway motion tracking results, and enable automatic and quantitative identification and analysis of in-treatment H&N upper airway motion. By integrating explicit and implicit linked-shape representations within a hierarchical model-fitting process, the proposed tracking method can process complex H&N structures and low-contrast/resolution cine MRI images. Future research will focus on the improvement of method reliability, patient motion pattern analysis for providing more information on patient-specific prediction of structure displacements, and motion effects on dosimetry for better H&N motion management in radiation therapy.

Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping.

PubMed

Henry, Roland G; Berman, Jeffrey I; Nagarajan, Srikantan S; Mukherjee, Pratik; Berger, Mitchel S

2004-02-01

The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain.

Subcortical pathways serving cortical language sites: initial experience with diffusion tensor imaging fiber tracking combined with intraoperative language mapping

PubMed Central

Henry, Roland G.; Berman, Jeffrey I.; Nagarajan, Srikantan S.; Mukherjee, Pratik; Berger, Mitchel S.

2014-01-01

The combination of mapping functional cortical neurons by intraoperative cortical stimulation and axonal architecture by diffusion tensor MRI fiber tracking can be used to delineate the pathways between functional regions. In this study the authors investigated the feasibility of combining these techniques to yield connectivity associated with motor speech and naming. Diffusion tensor MRI fiber tracking provides maps of axonal bundles and was combined with intraoperative mapping of eloquent cortex for a patient undergoing brain tumor surgery. Tracks from eight stimulated sites in the inferior frontal cortex including mouth motor, speech arrest, and anomia were generated from the diffusion tensor MRI data. The regions connected by the fiber tracking were compared to foci from previous functional imaging reports on language tasks. Connections were found between speech arrest, mouth motor, and anomia sites and the SMA proper and cerebral peduncle. The speech arrest and a mouth motor site were also seen to connect to the putamen via the external capsule. This is the first demonstration of delineation of subcortical pathways using diffusion tensor MRI fiber tracking with intraoperative cortical stimulation. The combined techniques may provide improved preservation of eloquent regions during neurological surgery, and may provide access to direct connectivity information between functional regions of the brain. PMID:14980564

Enhanced Positive-Contrast Visualization of Paramagnetic Contrast Agents Using Phase Images

PubMed Central

Mills, Parker H.; Ahrens, Eric T.

2009-01-01

Iron oxide–based MRI contrast agents are increasingly being used to noninvasively track cells, target molecular epitopes, and monitor gene expression in vivo. Detecting regions of contrast agent accumulation can be challenging if resulting contrast is subtle relative to endogenous tissue hypointensities. A postprocessing method is presented that yields enhanced positive-contrast images from the phase map associated with T2*-weighted MRI data. As examples, the method was applied to an agarose gel phantom doped with superparamagnetic iron-oxide nanoparticles and in vivo and ex vivo mouse brains inoculated with recombinant viruses delivering transgenes that induce overexpression of paramagnetic ferritin. Overall, this approach generates images that exhibit a 1- to 8-fold improvement in contrast-to-noise ratio in regions where paramagnetic agents are present compared to conventional magnitude images. This approach can be used in conjunction with conventional T2* pulse sequences, requires no prescans or increased scan time, and can be applied retrospectively to previously acquired data. PMID:19780169

Lesion registration for longitudinal disease tracking in an imaging informatics-based multiple sclerosis eFolder

NASA Astrophysics Data System (ADS)

Ma, Kevin; Liu, Joseph; Zhang, Xuejun; Lerner, Alex; Shiroishi, Mark; Amezcua, Lilyana; Liu, Brent

2016-03-01

We have designed and developed a multiple sclerosis eFolder system for patient data storage, image viewing, and automatic lesion quantification results stored in DICOM-SR format. The web-based system aims to be integrated in DICOM-compliant clinical and research environments to aid clinicians in patient treatments and data analysis. The system needs to quantify lesion volumes, identify and register lesion locations to track shifts in volume and quantity of lesions in a longitudinal study. In order to perform lesion registration, we have developed a brain warping and normalizing methodology using Statistical Parametric Mapping (SPM) MATLAB toolkit for brain MRI. Patients' brain MR images are processed via SPM's normalization processes, and the brain images are analyzed and warped according to the tissue probability map. Lesion identification and contouring are completed by neuroradiologists, and lesion volume quantification is completed by the eFolder's CAD program. Lesion comparison results in longitudinal studies show key growth and active regions. The results display successful lesion registration and tracking over a longitudinal study. Lesion change results are graphically represented in the web-based user interface, and users are able to correlate patient progress and changes in the MRI images. The completed lesion and disease tracking tool would enable the eFolder to provide complete patient profiles, improve the efficiency of patient care, and perform comprehensive data analysis through an integrated imaging informatics system.

Recent Advances in Superparamagnetic Iron Oxide Nanoparticles for Cellular Imaging and Targeted Therapy Research

PubMed Central

Wang, Yi-Xiang J.; Xuan, Shouhu; Port, Marc; Idee, Jean-Marc

2013-01-01

Advances of nanotechnology have led to the development of nanomaterials with both potential diagnostic and therapeutic applications. Among them, superparamagnetic iron oxide (SPIO) nanoparticles have received particular attention. Over the past decade, various SPIOs with unique physicochemical and biological properties have been designed by modifying the particle structure, size and coating. This article reviews the recent advances in preparing SPIOs with novel properties, the way these physicochemical properties of SPIOs influence their interaction with cells, and the development of SPIOs in liver and lymph nodes magnetic resonance imaging (MRI) contrast. Cellular uptake of SPIO can be exploited in a variety of potential clinical applications, including stem cell and inflammation cell tracking and intra-cellular drug delivery to cancerous cells which offers higher intra-cellular concentration. When SPIOs are used as carrier vehicle, additional advantages can be achieved including magnetic targeting and hyperthermia options, as well as monitoring with MRI. Other potential applications of SPIO include magnetofection and gene delivery, targeted retention of labeled stem cells, sentinel lymph nodes mapping, and magnetic force targeting and cell orientation for tissue engineering. PMID:23621536

Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study.

PubMed

Haast, Roy A M; Ivanov, Dimo; IJsselstein, Rutger J T; Sallevelt, Suzanne C E H; Jansen, Jacobus F A; Smeets, Hubert J M; de Coo, Irenaeus F M; Formisano, Elia; Uludağ, Kâmil

2018-01-01

One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N = 22) and healthy controls (N = 15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T 1 , T 2 * and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T 1 , T 2 * and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.

Integrated Eye Tracking and Neural Monitoring for Enhanced Assessment of Mild TBI

DTIC Science & Technology

2016-04-01

but these delays are nearing resolution and we anticipate the initiation of the neuroimaging portion of the study early in Year 3. The fMRI task...resonance imagining ( fMRI ) and diffusion tensor imaging (DTI) to characterize the extent of functional cortical recruitment and white matter injury...respectively. The inclusion of fMRI and DTI will provide an objective basis for cross-validating the EEG and eye tracking system. Both the EEG and eye

MRI - 3D Ultrasound - X-ray Image Fusion with Electromagnetic Tracking for Transendocardial Therapeutic Injections: In-vitro Validation and In-vivo Feasibility

PubMed Central

Hatt, Charles R.; Jain, Ameet K.; Parthasarathy, Vijay; Lang, Andrew; Raval, Amish N.

2014-01-01

Myocardial infarction (MI) is one of the leading causes of death in the world. Small animal studies have shown that stem-cell therapy offers dramatic functional improvement post-MI. An endomyocardial catheter injection approach to therapeutic agent delivery has been proposed to improve efficacy through increased cell retention. Accurate targeting is critical for reaching areas of greatest therapeutic potential while avoiding a life-threatening myocardial perforation. Multimodal image fusion has been proposed as a way to improve these procedures by augmenting traditional intra-operative imaging modalities with high resolution pre-procedural images. Previous approaches have suffered from a lack of real-time tissue imaging and dependence on X-ray imaging to track devices, leading to increased ionizing radiation dose. In this paper, we present a new image fusion system for catheter-based targeted delivery of therapeutic agents. The system registers real-time 3D echocardiography, magnetic resonance, X-ray, and electromagnetic sensor tracking within a single flexible framework. All system calibrations and registrations were validated and found to have target registration errors less than 5 mm in the worst case. Injection accuracy was validated in a motion enabled cardiac injection phantom, where targeting accuracy ranged from 0.57 to 3.81 mm. Clinical feasibility was demonstrated with in-vivo swine experiments, where injections were successfully made into targeted regions of the heart. PMID:23561056

Diffusion tensor tracking of neuronal fiber pathways in the living human brain

NASA Astrophysics Data System (ADS)

Lori, Nicolas Francisco

2001-11-01

The technique of diffusion tensor tracking (DTT) is described, in which diffusion tensor magnetic resonance imaging (DT-MRI) data are processed to allow the visualization of white matter (WM) tracts in a living human brain. To illustrate the methods, a detailed description is given of the physics of DT-MRI, the structure of the DT-MRI experiment, the computer tools that were developed to visualize WM tracts, the anatomical consistency of the obtained WM tracts, and the accuracy and precision of DTT using computer simulations. When presenting the physics of DT-MRI, a completely quantum-mechanical view of DT-MRI is given where some of the results are new. Examples of anatomical tracts viewed using DTT are presented, including the genu and the splenium of the corpus callosum, the ventral pathway with its amygdala connection highlighted, the geniculo- calcarine tract separated into anterior and posterior parts, the geniculo-calcarine tract defined using functional magnetic resonance imaging (MRI), and U- fibers. In the simulation, synthetic DT-MRI data were constructed that would be obtained for a cylindrical WM tract with a helical trajectory surrounded by gray matter. Noise was then added to the synthetic DT-MRI data, and DTT trajectories were calculated using the noisy data (realistic tracks). Simulated DTT errors were calculated as the vector distance between the realistic tracks and the ideal trajectory. The simulation tested the effects of a comprehensive set of experimental conditions, including voxel size, data sampling, data averaging, type of tract tissue, tract diameter and type of tract trajectory. Simulated DTT accuracy and precision were typically below the voxel dimension, and precision was compatible with the experimental results.

Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

PubMed Central

Sinharay, Sanhita; Pagel, Mark D.

2016-01-01

Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

Autonomous magnetic labelling of functional mesenchymal stem cells for improved traceability and spatial control in cell therapy applications.

PubMed

Harrison, Richard; Markides, Hareklea; Morris, Robert H; Richards, Paula; El Haj, Alicia J; Sottile, Virginie

2017-08-01

Mesenchymal stem cells (MSCs) represent a valuable resource for regenerative medicine treatments for orthopaedic repair and beyond. Following developments in isolation, expansion and differentiation protocols, efforts to promote clinical translation of emerging cellular strategies now seek to improve cell delivery and targeting. This study shows efficient live MSC labelling using silica-coated magnetic particles (MPs), which enables 3D tracking and guidance of stem cells. A procedure developed for the efficient and unassisted particle uptake was shown to support MSC viability and integrity, while surface marker expression and MSC differentiation capability were also maintained. In vitro, MSCs showed a progressive decrease in labelling over increasing culture time, which appeared to be linked to the dilution effect of cell division, rather than to particle release, and did not lead to detectable secondary particle uptake. Labelled MSC populations demonstrated magnetic responsiveness in vitro through directed migration in culture and, when seeded onto a scaffold, supporting MP-based approaches to cell targeting. The potential of these silica-coated MPs for MRI cell tracking of MSC populations was validated in 2D and in a cartilage repair model following cell delivery. These results highlight silica-coated magnetic particles as a simple, safe and effective resource to enhance MSC targeting for therapeutic applications and improve patient outcomes. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Real-time tracking of dissociation of hyperpolarized 89Y-DTPA: a model for degradation of open-chain Gd3+ MRI contrast agents

NASA Astrophysics Data System (ADS)

Ferguson, Sarah; Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Kovacs, Zoltan; Lumata, Lloyd

Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the 89Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T1 relaxation time of 89Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized 89Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd3+ MRI contrast agents will be discussed. This work was supported by the U.S. Department of Defense Award Number W81XWH-14-1-0048 and by the Robert A. Welch Foundation research Grant Number AT-1877.

Evaluation of lung tumor motion management in radiation therapy with dynamic MRI

NASA Astrophysics Data System (ADS)

Park, Seyoun; Farah, Rana; Shea, Steven M.; Tryggestad, Erik; Hales, Russell; Lee, Junghoon

2017-03-01

Surrogate-based tumor motion estimation and tracing methods are commonly used in radiotherapy despite the lack of continuous real time 3D tumor and surrogate data. In this study, we propose a method to simultaneously track the tumor and external surrogates with dynamic MRI, which allows us to evaluate their reproducible correlation. Four MRIcompatible fiducials are placed on the patient's chest and upper abdomen, and multi-slice 2D cine MRIs are acquired to capture the lung and whole tumor, followed by two-slice 2D cine MRIs to simultaneously track the tumor and fiducials, all in sagittal orientation. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and group-wise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D-2D template matching in which 3D tumor templates in 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model to the fiducial segmentations on the 2D cine MRIs. We tested our method on five lung cancer patients. Internal target volume from 4D-CT showed average sensitivity of 86.5% compared to the actual tumor motion for 5 min. 3D tumor motion correlated with the external surrogate signal, but showed a noticeable phase mismatch. The 3D tumor trajectory showed significant cycle-to-cycle variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from fiducials at different locations.

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

Anna-Liisa Brownell

Adult progenitor cells hold promise for therapeutic treatment where there has been a disabling loss of function due to death of cells from trauma, disease or aging. However, it will be essential in clinical application to be able to follow the fate of the transplanted cells over time using in vivo tracking methods. We have developed protocol for labeling of progenitor cells to monitor cell trafficking by high resolution magnetic resonance imaging (MRI) and super high resolution positron emission tomography (PET). We have transfected rat subventricular zone stem cells (SVZ, progenitor cell line) and another control cell line (PC12, pheochromocytomamore » cells) utilizing super paramagnetic iron oxide and poly-L-lysine complex for MR imaging or radiolabeling with 18F-fluor deoxy-D- glucose for PET imaging. The labeled cells were transplanted into the rostral migratory stream (RMS) or striatum of normal or 6-hydroxydopamine lesioned Spraque-Dawley rats. Longitudinal MRI studies (up to 40 days) showed that transplantation site has significant impact to the fate of the cells; when SVZ cells were transplanted into the RMS, cells migrated several centimeter into the olfactory bulb; after transplantation into the striatum, the migration was minimal, only 2 mm. PC 12 cells grew a massive tumor after the striatal implantation and significantly smaller tumor after the RMS implantation. PET studies conducted immediately after transplantation verified the transplantation site. MRI studies were able to show the whole path of migration in one image, since part of the cells die during migration and will get detected because of iron content. Endpoint histological studies verified the cell survival and immunohistochemical studies revealed the differentiation of the transplanted cells into astrocytes and neurons.« less

Behaviour of adipose-derived canine mesenchymal stem cells after superparamagnetic iron oxide nanoparticles labelling for magnetic resonance imaging.

PubMed

Kolecka, Malgorzata Anna; Arnhold, Stefan; Schmidt, Martin; Reich, Christine; Kramer, Martin; Failing, Klaus; von Pückler, Kerstin

2017-02-24

Therapy with mesenchymal stem cells (MSCs) has been reported to provide beneficial effects in the treatment of neurological and orthopaedic disorders in dogs. The exact mechanism of action is poorly understood. Magnetic resonance imaging (MRI) gives the opportunity to observe MSCs after clinical administration. To visualise MSCs with the help of MRI, labelling with an MRI contrast agent is necessary. However, it must be clarified whether there is any negative influence on cell function and viability after labelling prior to clinical administration. For the purpose of the study, seven samples with canine adipose-derived stem cells were incubated with superparamagnetic iron oxide nanoparticles (SPIO: 319.2 μg/mL Fe) for 24 h. The internalisation of the iron particles occurred via endocytosis. SPIO particles were localized as free clusters in the cytoplasm or within lysosomes depending on the time of investigation. The efficiency of the labelling was investigated using Prussian blue staining and MACS assay. After 3 weeks the percentage of SPIO labelled canine stem cells decreased. Phalloidin staining showed no negative effect on the cytoskeleton. Labelled cells underwent osteogenic and adipogenic differentiation. Chondrogenic differentiation occurred to a lesser extent compared with a control sample. MTT-Test and wound healing assay showed no influence of labelling on the proliferation. The duration of SPIO labelling was assessed using a 1 Tesla clinical MRI scanner and T2 weighted turbo spin echo and T2 weighted gradient echo MRI sequences 1, 2 and 3 weeks after labelling. The hypointensity caused by SPIO lasted for 3 weeks in both sequences. An Endorem labelling concentration of 319.2 μg/mL Fe (448 μg/mL SPIO) had no adverse effects on the viability of canine ASCs. Therefore, this contrast agent could be used as a model for iron oxide labelling agents. However, the tracking ability in vivo has to be evaluated in further studies.

Shoulder-Mounted Robot for MRI-guided arthrography: Accuracy and mounting study.

PubMed

Monfaredi, R; Wilson, E; Sze, R; Sharma, K; Azizi, B; Iordachita, I; Cleary, K

2015-08-01

A new version of our compact and lightweight patient-mounted MRI-compatible 4 degree-of-freedom (DOF) robot for MRI-guided arthrography procedures is introduced. This robot could convert the traditional two-stage arthrography procedure (fluoroscopy-guided needle insertion followed by a diagnostic MRI scan) to a one-stage procedure, all in the MRI suite. The results of a recent accuracy study are reported. A new mounting technique is proposed and the mounting stability is investigated using optical and electromagnetic tracking on an anthropomorphic phantom. Five volunteer subjects including 2 radiologists were asked to conduct needle insertion in 4 different random positions and orientations within the robot's workspace and the displacement of the base of the robot was investigated during robot motion and needle insertion. Experimental results show that the proposed mounting method is stable and promising for clinical application.

A Technique for Generating Volumetric Cine-Magnetic Resonance Imaging

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

Harris, Wendy; Ren, Lei, E-mail: lei.ren@duke.edu; Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina

Purpose: The purpose of this study was to develop a techique to generate on-board volumetric cine-magnetic resonance imaging (VC-MRI) using patient prior images, motion modeling, and on-board 2-dimensional cine MRI. Methods and Materials: One phase of a 4-dimensional MRI acquired during patient simulation is used as patient prior images. Three major respiratory deformation patterns of the patient are extracted from 4-dimensional MRI based on principal-component analysis. The on-board VC-MRI at any instant is considered as a deformation of the prior MRI. The deformation field is represented as a linear combination of the 3 major deformation patterns. The coefficients of themore » deformation patterns are solved by the data fidelity constraint using the acquired on-board single 2-dimensional cine MRI. The method was evaluated using both digital extended-cardiac torso (XCAT) simulation of lung cancer patients and MRI data from 4 real liver cancer patients. The accuracy of the estimated VC-MRI was quantitatively evaluated using volume-percent-difference (VPD), center-of-mass-shift (COMS), and target tracking errors. Effects of acquisition orientation, region-of-interest (ROI) selection, patient breathing pattern change, and noise on the estimation accuracy were also evaluated. Results: Image subtraction of ground-truth with estimated on-board VC-MRI shows fewer differences than image subtraction of ground-truth with prior image. Agreement between normalized profiles in the estimated and ground-truth VC-MRI was achieved with less than 6% error for both XCAT and patient data. Among all XCAT scenarios, the VPD between ground-truth and estimated lesion volumes was, on average, 8.43 ± 1.52% and the COMS was, on average, 0.93 ± 0.58 mm across all time steps for estimation based on the ROI region in the sagittal cine images. Matching to ROI in the sagittal view achieved better accuracy when there was substantial breathing pattern change. The technique was robust against noise levels up to SNR = 20. For patient data, average tracking errors were less than 2 mm in all directions for all patients. Conclusions: Preliminary studies demonstrated the feasibility of generating real-time VC-MRI for on-board localization of moving targets in radiation therapy.« less

Fluorine-19 Labeling of Stromal Vascular Fraction Cells for Clinical Imaging Applications

PubMed Central

Rose, Laura C.; Kadayakkara, Deepak K.; Wang, Guan; Bar-Shir, Amnon; Helfer, Brooke M.; O’Hanlon, Charles F.; Kraitchman, Dara L.; Rodriguez, Ricardo L.

2015-01-01

Stromal vascular fraction (SVF) cells are used clinically for various therapeutic targets. The location and persistence of engrafted SVF cells are important parameters for determining treatment failure versus success. We used the GID SVF-1 platform and a clinical protocol to harvest and label SVF cells with the fluorinated (19F) agent CS-1000 as part of a first-in-human phase I trial (clinicaltrials.gov identifier NCT02035085) to track SVF cells with magnetic resonance imaging during treatment of radiation-induced fibrosis in breast cancer patients. Flow cytometry revealed that SVF cells consisted of 25.0% ± 15.8% CD45+, 24.6% ± 12.5% CD34+, and 7.5% ± 3.3% CD31+ cells, with 2.1 ± 0.7 × 105 cells per cubic centimeter of adipose tissue obtained. Fluorescent CS-1000 (CS-ATM DM Green) labeled 87.0% ± 13.5% of CD34+ progenitor cells compared with 47.8% ± 18.5% of hematopoietic CD45+ cells, with an average of 2.8 ± 2.0 × 1012 19F atoms per cell, determined using nuclear magnetic resonance spectroscopy. The vast majority (92.7% ± 5.0%) of CD31+ cells were also labeled, although most coexpressed CD34. Only 16% ± 22.3% of CD45−/CD31−/CD34− (triple-negative) cells were labeled with CS-ATM DM Green. After induction of cell death by either apoptosis or necrosis, >95% of 19F was released from the cells, indicating that fluorine retention can be used as a surrogate marker for cell survival. Labeled-SVF cells engrafted in a silicone breast phantom could be visualized with a clinical 3-Tesla magnetic resonance imaging scanner at a sensitivity of approximately 2 × 106 cells at a depth of 5 mm. The current protocol can be used to image transplanted SVF cells at clinically relevant cell concentrations in patients. Significance Stromal vascular fraction (SVF) cells harvested from adipose tissue offer great promise in regenerative medicine, but methods to track such cell therapies are needed to ensure correct administration and monitor survival. A clinical protocol was developed to harvest and label SVF cells with the fluorinated (19F) agent CS-1000, allowing cells to be tracked with 19F magnetic resonance imaging (MRI). Flow cytometry evaluation revealed heterogeneous 19F uptake in SVF cells, confirming the need for careful characterization. The proposed protocol resulted in sufficient 19F uptake to allow imaging using a clinical MRI scanner with point-of-care processing. PMID:26511652

SU-G-BRA-03: PCA Based Imaging Angle Optimization for 2D Cine MRI Based Radiotherapy Guidance

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

Chen, T; Yue, N; Jabbour, S

2016-06-15

Purpose: To develop an imaging angle optimization methodology for orthogonal 2D cine MRI based radiotherapy guidance using Principal Component Analysis (PCA) of target motion retrieved from 4DCT. Methods: We retrospectively analyzed 4DCT of 6 patients with lung tumor. A radiation oncologist manually contoured the target volume at the maximal inhalation phase of the respiratory cycle. An object constrained deformable image registration (DIR) method has been developed to track the target motion along the respiration at ten phases. The motion of the center of the target mass has been analyzed using the PCA to find out the principal motion components thatmore » were uncorrelated with each other. Two orthogonal image planes for cineMRI have been determined using this method to minimize the through plane motion during MRI based radiotherapy guidance. Results: 3D target respiratory motion for all 6 patients has been efficiently retrieved from 4DCT. In this process, the object constrained DIR demonstrated satisfactory accuracy and efficiency to enable the automatic motion tracking for clinical application. The average motion amplitude in the AP, lateral, and longitudinal directions were 3.6mm (min: 1.6mm, max: 5.6mm), 1.7mm (min: 0.6mm, max: 2.7mm), and 5.6mm (min: 1.8mm, max: 16.1mm), respectively. Based on PCA, the optimal orthogonal imaging planes were determined for cineMRI. The average angular difference between the PCA determined imaging planes and the traditional AP and lateral imaging planes were 47 and 31 degrees, respectively. After optimization, the average amplitude of through plane motion reduced from 3.6mm in AP images to 2.5mm (min:1.3mm, max:3.9mm); and from 1.7mm in lateral images to 0.6mm (min: 0.2mm, max:1.5mm), while the principal in plane motion amplitude increased from 5.6mm to 6.5mm (min: 2.8mm, max: 17mm). Conclusion: DIR and PCA can be used to optimize the orthogonal image planes of cineMRI to minimize the through plane motion during radiotherapy guidance.« less

Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

PubMed Central

Polli, Roberson S.; Malheiros, Jackeline M.; dos Santos, Renan; Hamani, Clement; Longo, Beatriz M.; Tannús, Alberto; Mello, Luiz E.; Covolan, Luciene

2014-01-01

Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human temporal lobe epilepsy (TLE) but the distribution and severity of structural lesions between these two models may differ. Magnetic resonance imaging (MRI) studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation time and volume, but simultaneous comparative results have not been reported yet. The aim of this study was to compare the MRI T2HP and volume with histological data and frequency of seizures in both models. KA- and PILO-treated rats were imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS) frequency over the 9 months following status epilepticus (SE). Compared to controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3 months post SE. In contrast, hippocampal volume was unchanged in PILO-treated animals despite detectable increased T2HP and cell loss in granule cell layer, CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3 cells was smaller than age-matched CTL group. In contrast, PILO group had MRI volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells. In this group, T2HP signal was unaltered at 6 or 9 months after status. Reductions in the number of cells were not progressive in both models. Notably, the SRS frequency was higher in PILO than in the KA model. The volumetry data correlated well with tissue damage in the epileptic brain, suggesting that MRI may be useful for tracking longitudinal hippocampal changes, allowing the assessment of individual variability and disease progression. Our results indicate that the temporal changes in hippocampal morphology are distinct for both models of TLE and that these are not significantly correlated to the frequency of SRS. PMID:25071699

On the suitability of Elekta’s Agility 160 MLC for tracked radiation delivery: closed-loop machine performance

NASA Astrophysics Data System (ADS)

Glitzner, M.; Crijns, S. P. M.; de Senneville, B. Denis; Lagendijk, J. J. W.; Raaymakers, B. W.

2015-03-01

For motion adaptive radiotherapy, dynamic multileaf collimator tracking can be employed to reduce treatment margins by steering the beam according to the organ motion. The Elekta Agility 160 MLC has hitherto not been evaluated for its tracking suitability. Both dosimetric performance and latency are key figures and need to be assessed generically, independent of the used motion sensor. In this paper, we propose the use of harmonic functions directly fed to the MLC to determine its latency during continuous motion. Furthermore, a control variable is extracted from a camera system and fed to the MLC. Using this setup, film dosimetry and subsequent γ statistics are performed, evaluating the response when tracking (MRI)-based physiologic motion in a closed-loop. The delay attributed to the MLC itself was shown to be a minor contributor to the overall feedback chain as compared to the impact of imaging components such as MRI sequences. Delay showed a linear phase behaviour of the MLC employed in continuously dynamic applications, which enables a general MLC-characterization. Using the exemplary feedback chain, dosimetry showed a vast increase in pass rate employing γ statistics. In this early stage, the tracking performance of the Agility using the test bench yielded promising results, making the technique eligible for translation to tracking using clinical imaging modalities.

Three-dimensional spatiotemporal tracking of fluorine-18 radiolabeled yeast cells via positron emission particle tracking

DOE PAGES

Langford, Seth T.; Wiggins, Cody S.; Santos, Roque; ...

2017-07-06

A method for Positron Emission Particle Tracking (PEPT) based on optical feature point identification techniques is demonstrated for use in low activity tracking experiments. Furthermore, a population of yeast cells of approximately 125,000 members is activated to roughly 55 Bq/cell by 18F uptake. An in vitro particle tracking experiment is performed with nearly 20 of these cells after decay to 32 Bq/cell. These cells are successfully identified and tracked simultaneously in this experiment. Our work extends the applicability of PEPT as a cell tracking method by allowing a number of cells to be tracked together, and demonstrating tracking for verymore » low activity tracers.« less

Three-dimensional spatiotemporal tracking of fluorine-18 radiolabeled yeast cells via positron emission particle tracking

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

Langford, Seth T.; Wiggins, Cody S.; Santos, Roque

A method for Positron Emission Particle Tracking (PEPT) based on optical feature point identification techniques is demonstrated for use in low activity tracking experiments. Furthermore, a population of yeast cells of approximately 125,000 members is activated to roughly 55 Bq/cell by 18F uptake. An in vitro particle tracking experiment is performed with nearly 20 of these cells after decay to 32 Bq/cell. These cells are successfully identified and tracked simultaneously in this experiment. Our work extends the applicability of PEPT as a cell tracking method by allowing a number of cells to be tracked together, and demonstrating tracking for verymore » low activity tracers.« less

In situ preparation of high relaxivity iron oxide nanoparticles by coating with chitosan: A potential MRI contrast agent useful for cell tracking

NASA Astrophysics Data System (ADS)

Tsai, Zei-Tsan; Wang, Jen-Fei; Kuo, Hsiao-Yun; Shen, Chia-Rui; Wang, Jiun-Jie; Yen, Tzu-Chen

2010-01-01

Iron oxide nanocrystals are of considerable interest in nanoscience and nanotechnology because of their nanoscale dimensions, nontoxic nature, and superior magnetic properties. Colloidal solutions of magnetic nanoparticles (ferrofluids) with a high magnetite content are highly desirable for most molecular imaging applications. In this paper, we present a method for in situ coating of superparamagnetic iron oxide (SPIO) with chitosan in order to increase the content of magnetite. Iron chloride salts (Fe 3+ and Fe 2+) were directly coprecipitated inside a porous matrix of chitosan by Co-60 γ-ray irradiation in an aqueous solution of acetic acid. Following sonication, iron oxide nanoparticles were formed inside the chitosan matrix at a pH value of 9.5 and a temperature of 50 °C. The [Fe 3+]:[Fe 2+]:[NH 4OH] molar ratio was 1.6:1:15.8. The final ferrofluid was formed with a pH adjustment to approximately 2.0/3.0, alongside with the addition of mannitol and lactic acid. We subsequently characterized the particle size, the zeta potential, the iron concentration, the magnetic contrast, and the cellular uptake of our ferrofluid. Results showed a z-average diameter of 87.2 nm, a polydispersity index (PDI) of 0.251, a zeta potential of 47.9 mV, and an iron concentration of 10.4 mg Fe/mL. The MRI parameters included an R1 value of 22.0 mM -1 s -1, an R2 value of 202.6 mM -1 s -1, and a R2/R1 ratio of 9.2. An uptake of the ferrofluid by mouse macrophages was observed. Altogether, our data show that Co-60 γ-ray radiation on solid chitosan may improve chitosan coating of iron oxide nanoparticles and tackle its aqueous solubility at pH 7. Additionally, our methodology allowed to obtain a ferrofluid with a higher content of magnetite and a fairly unimodal distribution of monodisperse clusters. Finally, MRI and cell experiments demonstrated the potential usefulness of this product as a potential MRI contrast agent that might be used for cell tracking.

CORRELATION OF MRI GRADING OF BONE STRESS INJURIES WITH CLINICAL RISK FACTORS AND RETURN TO PLAY: A 5-YEAR PROSPECTIVE STUDY IN COLLEGIATE TRACK AND FIELD ATHLETES

PubMed Central

Nattiv, Aurelia; Kennedy, Gannon; Barrack, Michelle T.; Abdelkerim, Ashraf; Goolsby, Marci A.; Arends, Julie C.; Seeger, Leanne L.

2015-01-01

Background Bone stress injuries are common in track and field athletes. Knowledge of risk factors and correlation of these to magnetic resonance imaging (MRI) grading could be helpful in determining recovery time. Purpose To examine the relationships between MRI grading of bone stress injury with clinical risk factors and time to return to sport in collegiate track and field athletes. Study Design Prospective cohort over 5 years. Methods Two hundred and eleven male and female collegiate track and field and cross-country athletes were followed prospectively through their competitive seasons. All athletes had a pre-participation history, physical exam, and anthropometric measurements obtained annually. An additional questionnaire was completed regarding nutritional behaviors, menstrual patterns and prior injuries, as well as a 3-day diet record. Dual energy X-ray absorptiometry was obtained at baseline and each year of participation in the study. Athletes with clinical evidence of bone stress injuries had plain radiographs. If radiographs were negative, MRI was obtained. Bone stress injuries were evaluated by two independent radiologists utilizing an MRI grading system. MRI grading and risk factors were evaluated to identify predictors of time to return to sport. Results Thirty-four (12 males, 22 females) of the 211 collegiate athletes sustained 61 bone stress injuries during the 5-year study period. The average prospective assessment for participants was 2.1 years. MRI grade and total body bone mineral density (BMD) emerged as significant and independent predictors of time to return to sport in the multiple regression model. Specifically, the higher the MRI grade, the longer the recovery time (p<0.002). Location of bone injury at predominantly trabecular sites of the femoral neck, pubic bone and sacrum (p<0.001), and lower total body BMD (p<0.029) independently predicted prolonged time to return to sport. Conclusions Higher MRI grade, lower BMD, and skeletal sites of predominant trabecular bone structure were independently associated with delayed recovery of bone stress injuries in track and field athletes. Knowledge of these risk factors, as well as nutritional and menstrual factors, can be clinically useful in determining time to return to sport. PMID:23825184

Procedural Learning and Associative Memory Mechanisms Contribute to Contextual Cueing: Evidence from fMRI and Eye-Tracking

ERIC Educational Resources Information Center

Manelis, Anna; Reder, Lynne M.

2012-01-01

Using a combination of eye tracking and fMRI in a contextual cueing task, we explored the mechanisms underlying the facilitation of visual search for repeated spatial configurations. When configurations of distractors were repeated, greater activation in the right hippocampus corresponded to greater reductions in the number of saccades to locate…

Metastatic Renal Cell Carcinoma Masquerading as Jugular Foramen Paraganglioma: A Role for Novel Magnetic Resonance Imaging.

PubMed

Thomas, Andrew J; Wiggins, Richard H; Gurgel, Richard K

2017-08-01

To describe a case of metastatic renal cell carcinoma (RCC) masquerading as a jugular foramen paraganglioma (JP). To compare imaging findings between skull base metastatic RCC and histologically proven paraganglioma. A case of unexpected metastatic skull base RCC is reviewed. Computed tomography (CT) and magnetic resonance imaging (MRI) were compared between 3 confirmed cases of JP and our case of metastatic RCC. Diffusion-weighted MRI (DW-MRI) sequences and computed apparent diffusion coefficient (ADC) values were compared between these entities. A 55-year-old man presents with what appears clinically and radiographically to be JP. The tumor was resected, then discovered on postoperative pathology to be metastatic RCC. Imaging was retrospectively compared between 3 histologically confirmed cases of JP and our case of skull base RCC. The RCC metastasis was indistinguishable from JP on CT and traditional MRI but distinct by ADC values calculated from DW-MRI. Metastatic RCC at the skull base may mimic the clinical presentation and radiographic appearance of JP. The MRI finding of flow voids is seen in both paraganglioma and metastatic RCC. Diffusion-weighted MRI is able to distinguish these entities, highlighting its potential utility in distinguishing skull base lesions.

Tracking Cognitive Change over 24 Weeks with Longitudinal Functional Magnetic Resonance Imaging in Alzheimer's Disease

PubMed Central

McLaren, Donald G.; Sreenivasan, Aishwarya; Diamond, Eli L.; Mitchell, Meghan B.; Van Dijk, Koene R.A.; DeLuca, Amy N.; O’Brien, Jacqueline L.; Rentz, Dorene M.; Sperling, Reisa A.; Atri, Alireza

2012-01-01

Background Previous studies have revealed that functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal in specific brain regions correlates with cross-sectional performance on standardized clinical trial measures in Alzheimer's disease (AD); however, the relationship between longitudinal change in fMRI-BOLD signal and neuropsychological performance remains unknown. Objective: To identify changes in regional fMRI-BOLD activity that tracks change in neuropsychological performance in mild AD dementia over 6 months. Methods Twenty-four subjects (mean age 71.6) with mild AD dementia (mean Mini Mental State Examination 21.7, Global Clinical Dementia Rating 1.0) on stable donepezil dosing participated in two task-related fMRI sessions consisting of a face-name paired associative encoding memory paradigm 24 weeks apart during a randomized placebo-controlled pharmaco-fMRI drug study. Regression analysis was used to identify regions where the change in fMRI activity for Novel > Repeated stimulus contrast was associated with the change scores on postscan memory tests and the Free and Cued Selective Reminding Test (FCSRT). Results Correlations between changes in postscan memory accuracy and changes in fMRI activity were observed in regions including the angular gyrus, parahippocampal gyrus, inferior frontal gyrus and cerebellum. Correlations between changes in FCSRT-free recall and changes in fMRI were observed in regions including the inferior parietal lobule, precuneus, hippocampus and parahippocampal gyrus. Conclusion Changes in encoding-related fMRI activity in regions implicated in mnemonic networks correlated with changes in psychometric measures of episodic memory retrieval performed outside the scanner. These exploratory results support the potential of fMRI activity to track cognitive change and detect signals of short-term pharmacologic effect in early-phase AD studies. PMID:22456451

Tracking cognitive change over 24 weeks with longitudinal functional magnetic resonance imaging in Alzheimer's disease.

PubMed

McLaren, Donald G; Sreenivasan, Aishwarya; Diamond, Eli L; Mitchell, Meghan B; Van Dijk, Koene R A; Deluca, Amy N; O'Brien, Jacqueline L; Rentz, Dorene M; Sperling, Reisa A; Atri, Alireza

2012-01-01

Previous studies have revealed that functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal in specific brain regions correlates with cross-sectional performance on standardized clinical trial measures in Alzheimer's disease (AD); however, the relationship between longitudinal change in fMRI-BOLD signal and neuropsychological performance remains unknown. To identify changes in regional fMRI-BOLD activity that tracks change in neuropsychological performance in mild AD dementia over 6 months. Twenty-four subjects (mean age 71.6) with mild AD dementia (mean Mini Mental State Examination 21.7, Global Clinical Dementia Rating 1.0) on stable donepezil dosing participated in two task-related fMRI sessions consisting of a face-name paired associative encoding memory paradigm 24 weeks apart during a randomized placebo-controlled pharmaco-fMRI drug study. Regression analysis was used to identify regions where the change in fMRI activity for Novel > Repeated stimulus contrast was associated with the change scores on postscan memory tests and the Free and Cued Selective Reminding Test (FCSRT). Correlations between changes in postscan memory accuracy and changes in fMRI activity were observed in regions including the angular gyrus, parahippocampal gyrus, inferior frontal gyrus and cerebellum. Correlations between changes in FCSRT-free recall and changes in fMRI were observed in regions including the inferior parietal lobule, precuneus, hippocampus and parahippocampal gyrus. Changes in encoding-related fMRI activity in regions implicated in mnemonic networks correlated with changes in psychometric measures of episodic memory retrieval performed outside the scanner. These exploratory results support the potential of fMRI activity to track cognitive change and detect signals of short-term pharmacologic effect in early-phase AD studies. Copyright © 2012 S. Karger AG, Basel.

Changed processing of visual sexual stimuli under GnRH-therapy--a single case study in pedophilia using eye tracking and fMRI.

PubMed

Jordan, Kirsten; Fromberger, Peter; Laubinger, Helge; Dechent, Peter; Müller, Jürgen L

2014-05-17

Antiandrogen therapy (ADT) has been used for 30 years to treat pedophilic patients. The aim of the treatment is a reduction in sexual drive and, in consequence, a reduced risk of recidivism. Yet the therapeutic success of antiandrogens is uncertain especially regarding recidivism. Meta-analyses and reviews report only moderate and often mutually inconsistent effects. Based on the case of a 47 year old exclusively pedophilic forensic inpatient, we examined the effectiveness of a new eye tracking method and a new functional magnetic resonance imaging (fMRI)-design in regard to the evaluation of ADT in pedophiles. We analyzed the potential of these methods in exploring the impact of ADT on automatic and controlled attentional processes in pedophiles. Eye tracking and fMRI measures were conducted before the initial ADT as well as four months after the onset of ADT. The patient simultaneously viewed an image of a child and an image of an adult while eye movements were measured. During the fMRI-measure the same stimuli were presented subliminally. Eye movements demonstrated that controlled attentional processes change under ADT, whereas automatic processes remained mostly unchanged. We assume that these results reflect either the increased ability of the patient to control his eye movements while viewing prepubertal stimuli or his better ability to manipulate his answer in a socially desirable manner. Unchanged automatic attentional processes could reflect the stable pedophilic preference of the patient. Using fMRI, the subliminal presentation of sexually relevant stimuli led to changed activation patterns under the influence of ADT in occipital and parietal brain regions, the hippocampus, and also in the orbitofrontal cortex. We suggest that even at an unconscious level ADT can lead to changed processing of sexually relevant stimuli, reflecting changes of cognitive and perceptive automatic processes. We are convinced that our experimental designs using eye tracking and fMRI could prospectively add additional and valuable information in the evaluation of ADT in paraphilic patients and sex offenders. But with respect to the limited significance of this single case study, these first results are preliminary and further studies have to be conducted with healthy subjects and patients.

Changed processing of visual sexual stimuli under GnRH-therapy – a single case study in pedophilia using eye tracking and fMRI

PubMed Central

2014-01-01

Background Antiandrogen therapy (ADT) has been used for 30 years to treat pedophilic patients. The aim of the treatment is a reduction in sexual drive and, in consequence, a reduced risk of recidivism. Yet the therapeutic success of antiandrogens is uncertain especially regarding recidivism. Meta-analyses and reviews report only moderate and often mutually inconsistent effects. Case presentation Based on the case of a 47 year old exclusively pedophilic forensic inpatient, we examined the effectiveness of a new eye tracking method and a new functional magnetic resonance imaging (fMRI)-design in regard to the evaluation of ADT in pedophiles. We analyzed the potential of these methods in exploring the impact of ADT on automatic and controlled attentional processes in pedophiles. Eye tracking and fMRI measures were conducted before the initial ADT as well as four months after the onset of ADT. The patient simultaneously viewed an image of a child and an image of an adult while eye movements were measured. During the fMRI-measure the same stimuli were presented subliminally. Eye movements demonstrated that controlled attentional processes change under ADT, whereas automatic processes remained mostly unchanged. We assume that these results reflect either the increased ability of the patient to control his eye movements while viewing prepubertal stimuli or his better ability to manipulate his answer in a socially desirable manner. Unchanged automatic attentional processes could reflect the stable pedophilic preference of the patient. Using fMRI, the subliminal presentation of sexually relevant stimuli led to changed activation patterns under the influence of ADT in occipital and parietal brain regions, the hippocampus, and also in the orbitofrontal cortex. We suggest that even at an unconscious level ADT can lead to changed processing of sexually relevant stimuli, reflecting changes of cognitive and perceptive automatic processes. Conclusion We are convinced that our experimental designs using eye tracking and fMRI could prospectively add additional and valuable information in the evaluation of ADT in paraphilic patients and sex offenders. But with respect to the limited significance of this single case study, these first results are preliminary and further studies have to be conducted with healthy subjects and patients. PMID:24885644

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

PubMed Central

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

2012-01-01

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

MO-FG-BRD-01: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management: Introduction and KV Tracking

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

Fahimian, B.

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

MO-FG-BRD-04: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management: MR Tracking

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

Low, D.

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

MO-FG-BRD-02: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management: MV Tracking

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

Berbeco, R.

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

MO-FG-BRD-03: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management: EM Tracking

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

Keall, P.

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

Motion-compensated compressed sensing for dynamic contrast-enhanced MRI using regional spatiotemporal sparsity and region tracking: Block LOw-rank Sparsity with Motion-guidance (BLOSM)

PubMed Central

Chen, Xiao; Salerno, Michael; Yang, Yang; Epstein, Frederick H.

2014-01-01

Purpose Dynamic contrast-enhanced MRI of the heart is well-suited for acceleration with compressed sensing (CS) due to its spatiotemporal sparsity; however, respiratory motion can degrade sparsity and lead to image artifacts. We sought to develop a motion-compensated CS method for this application. Methods A new method, Block LOw-rank Sparsity with Motion-guidance (BLOSM), was developed to accelerate first-pass cardiac MRI, even in the presence of respiratory motion. This method divides the images into regions, tracks the regions through time, and applies matrix low-rank sparsity to the tracked regions. BLOSM was evaluated using computer simulations and first-pass cardiac datasets from human subjects. Using rate-4 acceleration, BLOSM was compared to other CS methods such as k-t SLR that employs matrix low-rank sparsity applied to the whole image dataset, with and without motion tracking, and to k-t FOCUSS with motion estimation and compensation that employs spatial and temporal-frequency sparsity. Results BLOSM was qualitatively shown to reduce respiratory artifact compared to other methods. Quantitatively, using root mean squared error and the structural similarity index, BLOSM was superior to other methods. Conclusion BLOSM, which exploits regional low rank structure and uses region tracking for motion compensation, provides improved image quality for CS-accelerated first-pass cardiac MRI. PMID:24243528

Quantitative [Fe]MRI of PSMA-targeted SPIONs specifically discriminates among prostate tumor cell types based on their PSMA expression levels.

PubMed

Sillerud, Laurel O

2016-01-01

We report the development, experimental verification, and application of a general theory called [Fe]MRI (pronounced fem-ree) for the non-invasive, quantitative molecular magnetic resonance imaging (MRI) of added magnetic nanoparticles or other magnetic contrast agents in biological tissues and other sites. [Fe]MRI can easily be implemented on any MRI instrument, requiring only measurements of the background nuclear magnetic relaxation times (T1, T2) of the tissue of interest, injection of the magnetic particles, and the subsequent acquisition of a pair of T1-weighted and T2-weighted images. These images, converted into contrast images, are subtracted to yield a contrast difference image proportional to the absolute nanoparticle, iron concentration, ([Fe]) image. [Fe]MRI was validated with the samples of superparamagnetic iron oxide nanoparticles (SPIONs) both in agarose gels and bound to human prostate tumor cells. The [Fe]MRI measurement of the binding of anti-prostate specific membrane antigen (PSMA) conjugated SPIONs to PSMA-positive LNCaP and PSMA-negative DU145 cells in vitro allowed a facile discrimination among prostate tumor cell types based on their PSMA expression level. The low [Fe] detection limit of ~2 μM for SPIONs allows sensitive MRI of added iron at concentrations considerably below the US Food and Drug Administration's human iron dosage guidelines (<90 μM, 5 mg/kg).

Real-time adaptive methods for treatment of mobile organs by MRI-controlled high-intensity focused ultrasound.

PubMed

de Senneville, Baudouin Denis; Mougenot, Charles; Moonen, Chrit T W

2007-02-01

Focused ultrasound (US) is a unique and noninvasive technique for local deposition of thermal energy deep inside the body. MRI guidance offers the additional benefits of excellent target visualization and continuous temperature mapping. However, treating a moving target poses severe problems because 1) motion-related thermometry artifacts must be corrected, 2) the US focal point must be relocated according to the target displacement. In this paper a complete MRI-compatible, high-intensity focused US (HIFU) system is described together with adaptive methods that allow continuous MR thermometry and therapeutic US with real-time tracking of a moving target, online motion correction of the thermometry maps, and regional temperature control based on the proportional, integral, and derivative method. The hardware is based on a 256-element phased-array transducer with rapid electronic displacement of the focal point. The exact location of the target during US firing is anticipated using automatic analysis of periodic motions. The methods were tested with moving phantoms undergoing either rigid body or elastic periodical motions. The results show accurate tracking of the focal point. Focal and regional temperature control is demonstrated with a performance similar to that obtained with stationary phantoms. Copyright (c) 2007 Wiley-Liss, Inc.

Magnetic Resonance Imaging (MRI) Characterization of Perianal Fistulous Disease in a Rural Based Tertiary Hospital of North India.

PubMed

Chauhan, Narvir Singh; Sood, Dinesh; Shukla, Anurag

2016-01-01

To diagnose and characterize the perianal fistulous disease using Magnetic resonance imaging (MRI) in a hilly and rural area of North India. This prospective hospital based study was conducted for a period of one year from April 2014 to April 2015 in the departments of Radiodiagnosis and Surgery of our institute. A total of 50 consecutive patients presenting with perianal fistulous disease fulfilling the inclusion and exclusion criteria were included in the study and taken up for MRI. The perianal fistulae were classified according to St James University hospital classification and tracks were assessed with regard to anatomical plane, length, ramifications, abscess formation, enteric communication, external cutaneous opening, enhancement and suprasphincteric extension. Surgical correlation was done in 31 patients who opted for surgical treatment. Rest of the 19 patients preferred alternative medicine for treatment or chose to postpone their surgery. The disease was much more prevalent in males in comparison to females with male to female ratio of 24:1. Grade 4 was the most common type of fistula (34%) while Grade 5 was the least common type (4%).MRI showed a high sensitivity of 93.7% and positive predictive value (PPV) of 96.7% when correlated with surgical findings. A substantial number of patients (38%) preferred alternative medicine or non surgical form of treatment. MRI is a very sensitive modality for the evaluation of perianal fistula. In our study group, the disease predominantly affected middle aged men. Ramifications and abscesses were commonly seen, affecting nearly half of the patients and majority of the patients had active fistulous tracks with posteriorly located enteric opening. Overall, transsphincteric fistulae were most common. Significant number of patients avoided surgery or showed preference for non surgical treatment.

Influence of MRI contrast media on histamine release from mast cells.

PubMed

Kun, Tomasz; Jakubowski, Lucjusz

2012-07-01

Mast cells, owing to diversity of secreted mediators, play a crucial role in the regulation of inflammatory response. Together with basophils, mast cells constitute a central pathogenetic element of anaphylactic (IgE-dependent) and anaphylactoid (IgE-independent) reactions. In severe cases, generalized degranulation of mast cells may cause symptoms of anaphylactic shock. The influence of the classical, iodine-based contrast media on mastocyte degranulation has been fully described. Our objective was to determine the influence of the gadolinium-based MRI contrast media on histamine release from mast cells and to compare the activity of ionic and non-ionic preparations of contrast media. To determine the intensity of mast cell degranulation, we used an experimental model based on mastocytes isolated from rat peritoneal fluid. Purified suspensions of mast cells were incubated with various concentrations of Gd-DTPA and Gd-DTPA-BMA, and solutions of PEG 600 which served as a non-toxic osmotic stimulus. The intensity of mast cell activation was presented as mean percentage of histamine released from cells after incubation. The obtained results demonstrate that both ionic and non-ionic preparations of the MRI contrast media are able to induce mast cell degranulation in vitro. It was also proved that the non-ionic MRI contrast media stimulate mast cells markedly more weakly than ionic contrast media at identical concentration. The aforementioned results may suggest a more profitable safety profile of the non-ionic contrast preparations. We may also conclude that triggering of mast cell degranulation after incubation with the solutions of MRI contrast media results from non-specific osmotic stimulation and direct toxicity of free ionic residues.

MO-FG-BRD-00: Real-Time Imaging and Tracking Techniques for Intrafractional Motion Management

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

NONE

2015-06-15

Intrafraction target motion is a prominent complicating factor in the accurate targeting of radiation within the body. Methods compensating for target motion during treatment, such as gating and dynamic tumor tracking, depend on the delineation of target location as a function of time during delivery. A variety of techniques for target localization have been explored and are under active development; these include beam-level imaging of radio-opaque fiducials, fiducial-less tracking of anatomical landmarks, tracking of electromagnetic transponders, optical imaging of correlated surrogates, and volumetric imaging within treatment delivery. The Joint Imaging and Therapy Symposium will provide an overview of the techniquesmore » for real-time imaging and tracking, with special focus on emerging modes of implementation across different modalities. In particular, the symposium will explore developments in 1) Beam-level kilovoltage X-ray imaging techniques, 2) EPID-based megavoltage X-ray tracking, 3) Dynamic tracking using electromagnetic transponders, and 4) MRI-based soft-tissue tracking during radiation delivery. Learning Objectives: Understand the fundamentals of real-time imaging and tracking techniques Learn about emerging techniques in the field of real-time tracking Distinguish between the advantages and disadvantages of different tracking modalities Understand the role of real-time tracking techniques within the clinical delivery work-flow.« less

Initial clinical observations of intra- and interfractional motion variation in MR-guided lung SBRT.

PubMed

Thomas, David H; Santhanam, Anand; Kishan, Amar U; Cao, Minsong; Lamb, James; Min, Yugang; O'Connell, Dylan; Yang, Yingli; Agazaryan, Nzhde; Lee, Percy; Low, Daniel

2018-02-01

To evaluate variations in intra- and interfractional tumour motion, and the effect on internal target volume (ITV) contour accuracy, using deformable image registration of real-time two-dimensional-sagittal cine-mode MRI acquired during lung stereotactic body radiation therapy (SBRT) treatments. Five lung tumour patients underwent free-breathing SBRT treatments on the ViewRay system, with dose prescribed to a planning target volume (defined as a 3-6 mm expansion of the 4DCT-ITV). Sagittal slice cine-MR images (3.5 × 3.5 mm 2 pixels) were acquired through the centre of the tumour at 4 frames per second throughout the treatments (3-4 fractions of 21-32 min). Tumour gross tumour volumes (GTVs) were contoured on the first frame of the MR cine and tracked for the first 20 min of each treatment using offline optical-flow based deformable registration implemented on a GPU cluster. A ground truth ITV (MR-ITV 20 min ) was formed by taking the union of tracked GTV contours. Pseudo-ITVs were generated from unions of the GTV contours tracked over 10 s segments of image data (MR-ITV 10 s ). Differences were observed in the magnitude of median tumour displacement between days of treatments. MR-ITV 10 s areas were as small as 46% of the MR-ITV 20 min . An ITV offers a "snapshot" of breathing motion for the brief period of time the tumour is imaged on a specific day. Real-time MRI over prolonged periods of time and over multiple treatment fractions shows that ITV size varies. Further work is required to investigate the dosimetric effect of these results. Advances in knowledge: Five lung tumour patients underwent free-breathing MRI-guided SBRT treatments, and their tumours tracked using deformable registration of cine-mode MRI. The results indicate that variability of both intra- and interfractional breathing amplitude should be taken into account during planning of lung radiotherapy.

Real time MRI prostate segmentation based on wavelet multiscale products flow tracking.

PubMed

Flores-Tapia, Daniel; Venugopal, Niranjan; Thomas, Gabriel; McCurdy, Boyd; Ryner, Lawrence; Pistorius, Stephen

2010-01-01

Currently, prostate cancer is the third leading cause of cancer-related deaths among men in North America. As with many others types of cancer, early detection and treatment greatly increases the patient's chance of survival. Combined Magnetic Resonance Imaging and Spectroscopic Imaging (MRI/MRSI) techniques have became a reliable tool for early stage prostate cancer detection. Nevertheless, their performance is strongly affected by the determination of the region of interest (ROI) prior to data acquisition process. The process of executing prostate MRI/MRSI techniques can be significantly enhanced by segmenting the whole prostate. A novel method for segmentation of the prostate in MRI datasets is presented. This method exploits the different behavior presented by signal singularities and noise in the wavelet domain in order to accurately detect the borders around the prostate. The prostate contour is then traced by using a set of spatially variant rules that are based on prior knowledge about the general shape of the prostate. The proposed method yielded promising results when applied to clinical datasets.

Accurate tumor localization and tracking in radiation therapy using wireless body sensor networks.

PubMed

Pourhomayoun, Mohammad; Jin, Zhanpeng; Fowler, Mark

2014-07-01

Radiation therapy is an effective method to combat cancerous tumors by killing the malignant cells or controlling their growth. Knowing the exact position of the tumor is a very critical prerequisite in radiation therapy. Since the position of the tumor changes during the process of radiation therapy due to the patient׳s movements and respiration, a real-time tumor tracking method is highly desirable in order to deliver a sufficient dose of radiation to the tumor region without damaging the surrounding healthy tissues. In this paper, we develop a novel tumor positioning method based on spatial sparsity. We estimate the position by processing the received signals from only one implantable RF transmitter. The proposed method uses less number of sensors compared to common magnetic transponder based approaches. The performance of the proposed method is evaluated in two different cases: (1) when the tissue configuration is perfectly determined (acquired beforehand by MRI or CT) and (2) when there are some uncertainties about the tissue boundaries. The results demonstrate the high accuracy and performance of the proposed method, even when the tissue boundaries are imperfectly known. Copyright © 2014 Elsevier Ltd. All rights reserved.

Automated, contour-based tracking and analysis of cell behaviour over long time scales in environments of varying complexity and cell density.

PubMed

Baker, Richard M; Brasch, Megan E; Manning, M Lisa; Henderson, James H

2014-08-06

Understanding single and collective cell motility in model environments is foundational to many current research efforts in biology and bioengineering. To elucidate subtle differences in cell behaviour despite cell-to-cell variability, we introduce an algorithm for tracking large numbers of cells for long time periods and present a set of physics-based metrics that quantify differences in cell trajectories. Our algorithm, termed automated contour-based tracking for in vitro environments (ACTIVE), was designed for adherent cell populations subject to nuclear staining or transfection. ACTIVE is distinct from existing tracking software because it accommodates both variability in image intensity and multi-cell interactions, such as divisions and occlusions. When applied to low-contrast images from live-cell experiments, ACTIVE reduced error in analysing cell occlusion events by as much as 43% compared with a benchmark-tracking program while simultaneously tracking cell divisions and resulting daughter-daughter cell relationships. The large dataset generated by ACTIVE allowed us to develop metrics that capture subtle differences between cell trajectories on different substrates. We present cell motility data for thousands of cells studied at varying densities on shape-memory-polymer-based nanotopographies and identify several quantitative differences, including an unanticipated difference between two 'control' substrates. We expect that ACTIVE will be immediately useful to researchers who require accurate, long-time-scale motility data for many cells. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

An Assessment of Gadonanotubes as Magnetic Nanolabels for Improved Stem Cell Detection and Retention in Cardiomyoplasty

NASA Astrophysics Data System (ADS)

Tran, Lesa A.

In this work, gadolinium-based carbon nanocapsules are developed as a novel nanotechnology that addresses the shortcomings of current diagnostic and therapeutic methods of stem cell-based cardiomyoplasty. With cardiovascular disease (CVD) responsible for approximately 30% of deaths worldwide, the growing need for improved cardiomyoplasty has spurred efforts in nanomedicine to develop innovative techniques to enhance the therapeutic retention and diagnostic tracking of transplanted cells. Having previously been demonstrated as a high-performance T1-weighted magnetic resonance imaging (MRI) contrast agent, Gadonanotubes (GNTs) are shown for the first time to intracellularly label pig bone marrow-derived mesenchymal stem cells (MSCs). Without the use of a transfection agent, micromolar concentrations of GNTs deliver up to 109 Gd3+ ions per cell, allowing for MSCs to be visualized in a 1.5 T clinical MRI scanner. The cellular response to the intracellular incorporation of GNTs is also assessed, revealing that GNTs do not compromise the viability, differentiation potential, or phenotype characteristics of the MSCs. However, it is also found that GNT-labeled MSCs exhibit a decreased response to select cell adhesion proteins and experience a nonapoptotic, non-proliferative cell cycle arrest, from which the cells recover 48 h after GNT internalization. In tandem with developing GNTs as a new stem cell diagnostic agent, this current work also explores for the first time the therapeutic application of the magnetically-active GNTs as a magnetic facilitator to increase the retention of transplanted stem cells during cardiomyoplasty. In vitro flow chamber assays, ex vivo perfusion experiments, and in vivo porcine injection procedures all demonstrate the increased magnetic-assisted retention of GNT-labeled MSCs in the presence of an external magnetic field. These studies prove that GNTs are a powerful 'theranostic' agent that provides a novel platform to simultaneously monitor and improve the therapeutic nature of stem cells for the treatment of CVD. It is expected that this new nanotechnology will further catalyze the development of cellular cardiomyoplasty and other stem cellbased therapies for the prevention, detection, and treatment of human diseases.

Magnetically controllable 3D microtissues based on magnetic microcryogels.

PubMed

Liu, Wei; Li, Yaqian; Feng, Siyu; Ning, Jia; Wang, Jingyu; Gou, Maling; Chen, Huijun; Xu, Feng; Du, Yanan

2014-08-07

Microtissues on the scale of several hundred microns are a promising cell culture configuration resembling the functional tissue units in vivo. In contrast to conventional cell culture, handling of microtissues poses new challenges such as medium exchange, purification and maintenance of the microtissue integrity. Here, we developed magnetic microcryogels to assist microtissue formation with enhanced controllability and robustness. The magnetic microcryogels were fabricated on-chip by cryogelation and micro-molding which could endure extensive external forces such as fluidic shear stress during pipetting and syringe injection. The magnetically controllable microtissues were applied to constitute a novel separable 3D co-culture system realizing functional enhancement of the hepatic microtissues co-cultured with the stromal microtissues and easy purification of the hepatic microtissues for downstream drug testing. The magnetically controllable microtissues with pre-defined shapes were also applied as building blocks to accelerate the tissue assembly process under magnetic force for bottom-up tissue engineering. Finally, the magnetic microcryogels could be injected in vivo as cell delivery vehicles and tracked by MRI. The injectable magnetic microtissues maintained viability at the injection site indicating good retention and potential applications for cell therapy. The magnetic microcryogels are expected to significantly promote the microtissues as a promising cellular configuration for cell-based applications such as in drug testing, tissue engineering and regenerative therapy.

MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability

NASA Astrophysics Data System (ADS)

Chan, Kannie W. Y.; Liu, Guanshu; Song, Xiaolei; Kim, Heechul; Yu, Tao; Arifin, Dian R.; Gilad, Assaf A.; Hanes, Justin; Walczak, Piotr; van Zijl, Peter C. M.; Bulte, Jeff W. M.; McMahon, Michael T.

2013-03-01

Biocompatible nanomaterials and hydrogels have become an important tool for improving cell-based therapies by promoting cell survival and protecting cell transplants from immune rejection. Although their potential benefit has been widely evaluated, at present it is not possible to determine, in vivo, if and how long cells remain viable following their administration without the use of a reporter gene. Here, we report a pH-nanosensor-based magnetic resonance imaging (MRI) technique that can monitor cell death in vivo non-invasively. We demonstrate that specific MRI parameters that change on cell death of microencapsulated hepatocytes are associated with the measured bioluminescence imaging radiance. Moreover, the readout from this pH-sensitive nanosensor can be directly co-registered with high-resolution anatomical images. All of the components of these nanosensors are clinical grade and hence this approach should be a translatable and universal modification of hydrogels.

Violating instructed human agency: An fMRI study on ocular tracking of biological and nonbiological motion stimuli.

PubMed

Gertz, Hanna; Hilger, Maximilian; Hegele, Mathias; Fiehler, Katja

2016-09-01

Previous studies have shown that beliefs about the human origin of a stimulus are capable of modulating the coupling of perception and action. Such beliefs can be based on top-down recognition of the identity of an actor or bottom-up observation of the behavior of the stimulus. Instructed human agency has been shown to lead to superior tracking performance of a moving dot as compared to instructed computer agency, especially when the dot followed a biological velocity profile and thus matched the predicted movement, whereas a violation of instructed human agency by a nonbiological dot motion impaired oculomotor tracking (Zwickel et al., 2012). This suggests that the instructed agency biases the selection of predictive models on the movement trajectory of the dot motion. The aim of the present fMRI study was to examine the neural correlates of top-down and bottom-up modulations of perception-action couplings by manipulating the instructed agency (human action vs. computer-generated action) and the observable behavior of the stimulus (biological vs. nonbiological velocity profile). To this end, participants performed an oculomotor tracking task in an MRI environment. Oculomotor tracking activated areas of the eye movement network. A right-hemisphere occipito-temporal cluster comprising the motion-sensitive area V5 showed a preference for the biological as compared to the nonbiological velocity profile. Importantly, a mismatch between instructed human agency and a nonbiological velocity profile primarily activated medial-frontal areas comprising the frontal pole, the paracingulate gyrus, and the anterior cingulate gyrus, as well as the cerebellum and the supplementary eye field as part of the eye movement network. This mismatch effect was specific to the instructed human agency and did not occur in conditions with a mismatch between instructed computer agency and a biological velocity profile. Our results support the hypothesis that humans activate a specific predictive model for biological movements based on their own motor expertise. A violation of this predictive model causes costs as the movement needs to be corrected in accordance with incoming (nonbiological) sensory information. Copyright © 2016 Elsevier Inc. All rights reserved.

pH-Responsive, Self-Sacrificial Nanotheranostic Agent for Potential In Vivo and In Vitro Dual Modal MRI/CT Imaging, Real-Time, and In Situ Monitoring of Cancer Therapy.

PubMed

Yue, Ludan; Wang, Jinlong; Dai, Zhichao; Hu, Zunfu; Chen, Xue; Qi, Yafei; Zheng, Xiuwen; Yu, Dexin

2017-02-15

Multifunctional nanotheranostic agents have been highly commended due to the application to image-guided cancer therapy. Herein, based on the chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) and graphene oxide (GO), we develop a pH-responsive FePt-based multifunctional theranostic agent for potential in vivo and in vitro dual modal MRI/CT imaging and in situ cancer inhibition. The fcc-FePt will release highly active Fe ions due to the low pH in tumor cells, which would catalyze H 2 O 2 decomposition into reactive oxygen species (ROS) within the cells and further induce cancer cell apoptosis. Conjugated with folic acid (FA), the iron platinum-dimercaptosuccinnic acid/PEGylated graphene oxide-folic acid (FePt-DMSA/GO-PEG-FA) composite nanoassemblies (FePt/GO CNs) could effectively target and show significant toxicity to FA receptor-positive tumor cells, but no obvious toxicity to FA receptor-negative normal cells, which was evaluated by WST-1 assay. The FePt-based multifunctional nanoparticles allow real-time monitoring of Fe release by T 2 -weighted MRI, and the selective contrast enhancement in CT could be estimated in vivo after injection. The results showed that FePt-based NPs displayed excellent biocompatibility and favorable MRI/CT imaging ability in vivo and in vitro. Meanwhile, the decomposition of FePt will dramatically decrease the T 2 -weighted MRI signal and increase the ROS signal, which enables real-time and in situ visualized monitoring of Fe release in tumor cells. In addition, the self-sacrificial decomposition of fcc-FePt will be propitious to the self-clearance of the as-prepared FePt-based nanocomposite in vivo. Therefore, the FePt/GO CNs could serve as a potential multifunctional theranostic nanoplatform of MRI/CT imaging guided cancer diagnosis and therapy in the clinic.

Robust Revascularization in Models of Limb Ischemia Using a Clinically Translatable Human Stem Cell-Derived Endothelial Cell Product.

PubMed

MacAskill, Mark G; Saif, Jaimy; Condie, Alison; Jansen, Maurits A; MacGillivray, Thomas J; Tavares, Adriana A S; Fleisinger, Lucija; Spencer, Helen L; Besnier, Marie; Martin, Ernesto; Biglino, Giovanni; Newby, David E; Hadoke, Patrick W F; Mountford, Joanne C; Emanueli, Costanza; Baker, Andrew H

2018-03-28

Pluripotent stem cell-derived differentiated endothelial cells offer high potential in regenerative medicine in the cardiovascular system. With the aim of translating the use of a human stem cell-derived endothelial cell product (hESC-ECP) for treatment of critical limb ischemia (CLI) in man, we report a good manufacturing practice (GMP)-compatible protocol and detailed cell tracking and efficacy data in multiple preclinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP, which was identified as mostly endothelial (60% CD31 + /CD144 + ), with the remainder of the subset expressing various pericyte/mesenchymal stem cell markers. Cell tracking using MRI, PET, and qPCR in a murine model of limb ischemia demonstrated that hESC-ECP was detectable up to day 7 following injection. Efficacy in several murine models of limb ischemia (immunocompromised/immunocompetent mice and mice with either type I/II diabetes mellitus) demonstrated significantly increased blood perfusion and capillary density. Overall, we demonstrate a GMP-compatible hESC-ECP that improved ischemic limb perfusion and increased local angiogenesis without engraftment, paving the way for translation of this therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

SU-E-J-108: Template Matching Based On Multiple Templates Can Improve the Tumor Tracking Performance When There Is Large Tumor Deformation

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

Shi, X; Lin, J; Diwanji, T

2014-06-01

Purpose: Recently, template matching has been shown to be able to track tumor motion on cine-MRI images. However, artifacts such as deformation, rotation, and/or out-of-plane movement could seriously degrade the performance of this technique. In this work, we demonstrate the utility of multiple templates derived from different phases of tumor motion in reducing the negative effects of artifacts and improving the accuracy of template matching methods. Methods: Data from 2 patients with large tumors and significant tumor deformation were analyzed from a group of 12 patients from an earlier study. Cine-MRI (200 frames) imaging was performed while the patients weremore » instructed to breathe normally. Ground truth tumor position was established on each frame manually by a radiation oncologist. Tumor positions were also automatically determined using template matching with either single or multiple (5) templates. The tracking errors, defined as the absolute differences in tumor positions determined by the manual and automated methods, when using either single or multiple templates were compared in both the AP and SI directions, respectively. Results: Using multiple templates reduced the tracking error of template matching. In the SI direction where the tumor movement and deformation were significant, the mean tracking error decreased from 1.94 mm to 0.91 mm (Patient 1) and from 6.61 mm to 2.06 mm (Patient 2). In the AP direction where the tumor movement was small, the reduction of the mean tracking error was significant in Patient 1 (from 3.36 mm to 1.04 mm), but not in Patient 2 ( from 3.86 mm to 3.80 mm). Conclusion: This study shows the effectiveness of using multiple templates in improving the performance of template matching when artifacts like large tumor deformation or out-of-plane motion exists. Accurate tumor tracking capabilities can be integrated with MRI guided radiation therapy systems. This work was supported in part by grants from NIH/NCI CA 124766 and Varian Medical Systems, Palo Alto, CA.« less

Using ferromagnetic nanoparticles with low Curie temperature for magnetic resonance imaging-guided thermoablation.

PubMed

Herynek, Vít; Turnovcová, Karolína; Veverka, Pavel; Dědourková, Tereza; Žvátora, Pavel; Jendelová, Pavla; Gálisová, Andrea; Kosinová, Lucie; Jiráková, Klára; Syková, Eva

2016-01-01

Magnetic nanoparticles (NPs) represent a tool for use in magnetic resonance imaging (MRI)-guided thermoablation of tumors using an external high-frequency (HF) magnetic field. To avoid local overheating, perovskite NPs with a lower Curie temperature (T c) were proposed for use in thermotherapy. However, deposited power decreases when approaching the Curie temperature and consequently may not be sufficient for effective ablation. The goal of the study was to test this hypothesis. Perovskite NPs (T c =66°C-74°C) were characterized and tested both in vitro and in vivo. In vitro, the cells suspended with NPs were exposed to a HF magnetic field together with control samples. In vivo, a NP suspension was injected into a induced tumor in rats. Distribution was checked by MRI and the rats were exposed to a HF field together with control animals. Apoptosis in the tissue was evaluated. In vitro, the high concentration of suspended NPs caused an increase of the temperature in the cell sample, leading to cell death. In vivo, MRI confirmed distribution of the NPs in the tumor. The temperature in the tumor with injected NPs did not increase substantially in comparison with animals without particles during HF exposure. We proved that the deposited power from the NPs is too small and that thermoregulation of the animal is sufficient to conduct the heat away. Histology did not detect substantially higher apoptosis in NP-treated animals after ablation. Magnetic particles with low T c can be tracked in vivo by MRI and heated by a HF field. The particles are capable of inducing cell apoptosis in suspensions in vitro at high concentrations only. However, their effect in the case of extracellular deposition in vivo is questionable due to low deposited power and active thermoregulation of the tissue.

A spatiotemporal-based scheme for efficient registration-based segmentation of thoracic 4-D MRI.

PubMed

Yang, Y; Van Reeth, E; Poh, C L; Tan, C H; Tham, I W K

2014-05-01

Dynamic three-dimensional (3-D) (four-dimensional, 4-D) magnetic resonance (MR) imaging is gaining importance in the study of pulmonary motion for respiratory diseases and pulmonary tumor motion for radiotherapy. To perform quantitative analysis using 4-D MR images, segmentation of anatomical structures such as the lung and pulmonary tumor is required. Manual segmentation of entire thoracic 4-D MRI data that typically contains many 3-D volumes acquired over several breathing cycles is extremely tedious, time consuming, and suffers high user variability. This requires the development of new automated segmentation schemes for 4-D MRI data segmentation. Registration-based segmentation technique that uses automatic registration methods for segmentation has been shown to be an accurate method to segment structures for 4-D data series. However, directly applying registration-based segmentation to segment 4-D MRI series lacks efficiency. Here we propose an automated 4-D registration-based segmentation scheme that is based on spatiotemporal information for the segmentation of thoracic 4-D MR lung images. The proposed scheme saved up to 95% of computation amount while achieving comparable accurate segmentations compared to directly applying registration-based segmentation to 4-D dataset. The scheme facilitates rapid 3-D/4-D visualization of the lung and tumor motion and potentially the tracking of tumor during radiation delivery.

Evaluation of an image-based tracking workflow using a passive marker and resonant micro-coil fiducials for automatic image plane alignment in interventional MRI.

PubMed

Neumann, M; Breton, E; Cuvillon, L; Pan, L; Lorenz, C H; de Mathelin, M

2012-01-01

In this paper, an original workflow is presented for MR image plane alignment based on tracking in real-time MR images. A test device consisting of two resonant micro-coils and a passive marker is proposed for detection using image-based algorithms. Micro-coils allow for automated initialization of the object detection in dedicated low flip angle projection images; then the passive marker is tracked in clinical real-time MR images, with alternation between two oblique orthogonal image planes along the test device axis; in case the passive marker is lost in real-time images, the workflow is reinitialized. The proposed workflow was designed to minimize dedicated acquisition time to a single dedicated acquisition in the ideal case (no reinitialization required). First experiments have shown promising results for test-device tracking precision, with a mean position error of 0.79 mm and a mean orientation error of 0.24°.

Fast cine-magnetic resonance imaging point tracking for prostate cancer radiation therapy planning

NASA Astrophysics Data System (ADS)

Dowling, J.; Dang, K.; Fox, Chris D.; Chandra, S.; Gill, Suki; Kron, T.; Pham, D.; Foroudi, F.

2014-03-01

The analysis of intra-fraction organ motion is important for improving the precision of radiation therapy treatment delivery. One method to quantify this motion is for one or more observers to manually identify anatomic points of interest (POIs) on each slice of a cine-MRI sequence. However this is labour intensive and inter- and intra- observer variation can introduce uncertainty. In this paper a fast method for non-rigid registration based point tracking in cine-MRI sagittal and coronal series is described which identifies POIs in 0.98 seconds per sagittal slice and 1.35 seconds per coronal slice. The manual and automatic points were highly correlated (r>0.99, p<0.001) for all organs and the difference generally less than 1mm. For prostate planning peristalsis and rectal gas can result in unpredictable out of plane motion, suggesting the results may require manual verification.

Automated segmentation and tracking of non-rigid objects in time-lapse microscopy videos of polymorphonuclear neutrophils.

PubMed

Brandes, Susanne; Mokhtari, Zeinab; Essig, Fabian; Hünniger, Kerstin; Kurzai, Oliver; Figge, Marc Thilo

2015-02-01

Time-lapse microscopy is an important technique to study the dynamics of various biological processes. The labor-intensive manual analysis of microscopy videos is increasingly replaced by automated segmentation and tracking methods. These methods are often limited to certain cell morphologies and/or cell stainings. In this paper, we present an automated segmentation and tracking framework that does not have these restrictions. In particular, our framework handles highly variable cell shapes and does not rely on any cell stainings. Our segmentation approach is based on a combination of spatial and temporal image variations to detect moving cells in microscopy videos. This method yields a sensitivity of 99% and a precision of 95% in object detection. The tracking of cells consists of different steps, starting from single-cell tracking based on a nearest-neighbor-approach, detection of cell-cell interactions and splitting of cell clusters, and finally combining tracklets using methods from graph theory. The segmentation and tracking framework was applied to synthetic as well as experimental datasets with varying cell densities implying different numbers of cell-cell interactions. We established a validation framework to measure the performance of our tracking technique. The cell tracking accuracy was found to be >99% for all datasets indicating a high accuracy for connecting the detected cells between different time points. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

NASA Astrophysics Data System (ADS)

Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

2009-02-01

This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

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

Borot de Battisti, Maxence, E-mail: M.E.P.Borot@um

Purpose: The development of MR-guided high dose rate (HDR) brachytherapy is under investigation due to the excellent tumor and organs at risk visualization of MRI. However, MR-based localization of needles (including catheters or tubes) has inherently a low update rate and the required image interpretation can be hampered by signal voids arising from blood vessels or calcifications limiting the precision of the needle guidance and reconstruction. In this paper, a new needle tracking prototype is investigated using fiber Bragg gratings (FBG)-based sensing: this prototype involves a MR-compatible stylet composed of three optic fibers with nine sets of embedded FBG sensorsmore » each. This stylet can be inserted into brachytherapy needles and allows a fast measurement of the needle deflection. This study aims to assess the potential of FBG-based sensing for real-time needle (including catheter or tube) tracking during MR-guided intervention. Methods: First, the MR compatibility of FBG-based sensing and its accuracy was evaluated. Different known needle deflections were measured using FBG-based sensing during simultaneous MR-imaging. Then, a needle tracking procedure using FBG-based sensing was proposed. This procedure involved a MR-based calibration of the FBG-based system performed prior to the interventional procedure. The needle tracking system was assessed in an experiment with a moving phantom during MR imaging. The FBG-based system was quantified by comparing the gold-standard shapes, the shape manually segmented on MRI and the FBG-based measurements. Results: The evaluation of the MR compatibility of FBG-based sensing and its accuracy shows that the needle deflection could be measured with an accuracy of 0.27 mm on average. Besides, the FBG-based measurements were comparable to the uncertainty of MR-based measurements estimated at half the voxel size in the MR image. Finally, the mean(standard deviation) Euclidean distance between MR- and FBG-based needle position measurements was equal to 0.79 mm(0.37 mm). The update rate and latency of the FBG-based needle position measurement were 100 and 300 ms, respectively. Conclusions: The FBG-based needle tracking procedure proposed in this paper is able to determine the position of the complete needle, under MR-imaging, with better accuracy and precision, higher update rate, and lower latency compared to current MR-based needle localization methods. This system would be eligible for MR-guided brachytherapy, in particular, for an improved needle guidance and reconstruction.« less

Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury

DTIC Science & Technology

2012-11-01

testing and advanced MRI techniques [task-activated functional MRI (fMRI) and diffusion tensor imaging ( DTI )] to gain a comprehensive understanding of... DTI fiber tracking) and neurobehavioral testing (computerized assessment and standard neuropsychological testing) on 60 chronic trauma patients: 15...data analysis. 15. SUBJECT TERMS Blast-related traumatic brain injury (TBI), fMRI, DTI , cognition 16. SECURITY CLASSIFICATION OF: 17. LIMITATION

Label free cell-tracking and division detection based on 2D time-lapse images for lineage analysis of early embryo development.

PubMed

Cicconet, Marcelo; Gutwein, Michelle; Gunsalus, Kristin C; Geiger, Davi

2014-08-01

In this paper we report a database and a series of techniques related to the problem of tracking cells, and detecting their divisions, in time-lapse movies of mammalian embryos. Our contributions are (1) a method for counting embryos in a well, and cropping each individual embryo across frames, to create individual movies for cell tracking; (2) a semi-automated method for cell tracking that works up to the 8-cell stage, along with a software implementation available to the public (this software was used to build the reported database); (3) an algorithm for automatic tracking up to the 4-cell stage, based on histograms of mirror symmetry coefficients captured using wavelets; (4) a cell-tracking database containing 100 annotated examples of mammalian embryos up to the 8-cell stage; and (5) statistical analysis of various timing distributions obtained from those examples. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structural and functional network connectivity breakdown in Alzheimer’s disease studied with magnetic resonance imaging techniques.

PubMed

Filippi, Massimo; Agosta, Federica

2011-01-01

Patients with Alzheimer’s disease (AD) experience a brain network breakdown, reflecting disconnection at both the structural and functional system level. Resting-state (RS) functional MRI (fMRI) studies demonstrated that the regional coherence of the fMRI signal is significantly altered in patients with AD and amnestic mild cognitive impairment. Diffusion tensor (DT) MRI has made it possible to track fiber bundle projections across the brain, revealing a substantially abnormal interplay of “critical” white matter tracts in these conditions. The observed agreement between the results of RS fMRI and DT MRI tractography studies in healthy individuals is encouraging and offers interesting hypotheses to be tested in patients with AD, a MCI, and other dementias in order to improve our understanding of their pathobiology in vivo. In this review,we describe the major findings obtained in AD using RS fMRI and DT MRI tractography, and discuss how the relationship between structure and function of the brain networks in AD may be better understood through the application of MR-based technology. This research endeavor holds a great promise in clarifying the mechanisms of cognitive decline in complex chronic neurodegenerative disorders.

Labeling transplanted mice islet with polyvinylpyrrolidone coated superparamagnetic iron oxide nanoparticles for in vivo detection by magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Huang, Hai; Xie, Qiuping; Kang, Muxing; Zhang, Bo; Zhang, Hui; Chen, Jin; Zhai, Chuanxin; Yang, Deren; Jiang, Biao; Wu, Yulian

2009-09-01

Superparamagnetic iron oxide nanoparticles (SPIO) are emerging as a novel probe for noninvasive cell tracking with magnetic resonance imaging (MRI) and have potential wide usage in medical research. In this study, we have developed a method using high-temperature hydrolysis of chelate metal alkoxide complexes to synthesize polyvinylpyrrolidone coated iron oxide nanoparticles (PVP-SPIO), as a biocompatible magnetic agent that can efficiently label mice islet β-cells. The size, crystal structure and magnetic properties of the as-synthesized nanoparticles have been characterized. The newly synthesized PVP-SPIO with high stability, crystallinity and saturation magnetization can be efficiently internalized into β-cells, without affecting viability and function. The imaging of 100 PVP-SPIO-labeled mice islets in the syngeneic renal subcapsular model of transplantation under a clinical 3.0 T MR imager showed high spatial resolution in vivo. These results indicated the great potential application of the PVP-SPIO as an MRI contrast agent for monitoring transplanted islet grafts in the clinical management of diabetes in the near future.

Shape Effects in Nanoparticle-Based Imaging Agents

NASA Astrophysics Data System (ADS)

Culver, Kayla Shani Brook

At the nanoscale, material properties become highly size and shape dependent. These properties can be manipulated and exploited for a variety of biomedical applications, including sensing, drug delivery, diagnostics, and imaging. In particular, nanoparticles of different materials, sizes and shapes have been developed as high-performance contrast agents for optical, electron, and medical imaging. In this thesis, I focus on gold nanoparticles because they are widely used as contrast agents in multiple types of imaging modalities. Additionally, the surface of gold can be readily functionalized with ligands and the structure of the particles can be manipulated to modulate their performance as imaging agents. The properties of nanoparticles can generate contrast directly. For example, the light scattering properties of gold particles can be visualized in optical microscopy, the high electron density of gold produces contrast in electron microscopy, and the x-ray absorption properties of gold can be detected in medical x-ray and computed tomography imaging. Alternatively, the properties of the nanomaterial can be exploited to modulate the signal produced by other molecules that are bound to the particle surface. The light emission of molecular fluorophores can be quenched or dramatically increased by coupling to the optical field enhancements of gold nanoparticles, and the performance of gadolinium (Gd(III))-based magnetic resonance imaging (MRI) contrast agents can be increased by coupling to the rotational motion of nanoparticles. In this dissertation, I focus specifically on how the structure of star-shaped gold particles (nanostars) can be exploited as single-particle optical probes and to dramatically enhance the relaxivity of Gd(III) bound to the surface. Differential interference contrast (DIC) is a type of wide-field diffraction-limited optical microscopy that is commonly used by biologists to image cells without labels. Here, I demonstrate the DIC can be used to characterize complex nanoscale structural features and spectral properties of gold nanostars. Specifically, by evaluating the DIC contrast and image patterns of single nanostars, I distinguished between flat and 3D geometries, identified nanostars with 4-fold symmetry, and determined nanostar orientation. Additionally, in multi-wavelength DIC imaging, an inversion in the contrast could be used to indicate the localized surface plasmon resonance of nanostars with 1 and 2 branches. Next, I used DIC to track the rotational and translational dynamics of functionalized nanostars interacting with live cell membranes. The DNA aptamer ligand on the nanostars specifically targets the transmembrane receptor HER2. I tracked single nanoconstructs over long time scales (˜ 20 minutes per particle, > 80 minutes total) with high temporal resolution (4 fps) and found that analysis of the DIC contrast fluctuations could be used to identify multiple modes of rotational behavior on the cell membrane. I developed MATLAB programs to track the moving nanoconstructs in a dynamic background environment and set up a customized live-cell perfusion chamber that is compatible with the bulky high numerical aperture optics. The combination of the environmental control in the chamber and the low light levels required to visualize single nanostars make this technique optimal for long-term tracking of single nanoconstructs in viable cells. Although nanoparticle size is well-known to influence the relaxivity of Gd(III)-based MRI contrast agents that are attached to the surface, the role of nanoparticle shape was previously unknown. Recently, we discovered that the relaxivity of Gd(III)-conjugated DNA bound to nanostars was three-fold higher than that of analogous spherical nanoconstructs. The relaxivities reached enhancements that were beyond limits that could be explained theoretically by size effects alone. We found that the extremely large enhancements could be explained by elongated water residence times in the second coordination sphere. Here, we investigated in detail how the complex structure of the nanostars mediates these effects. By sorting the nanostars by shape, we found that relaxivity increases with increasing branch number. Thus, we hypothesize that the confinement of the Gd(III)-DNA in the regions of negative surface curvature between branches creates a dense hydrophilic environment that promotes relaxation of second-sphere water molecules. These results demonstrate that shape is a new parameter that can be tuned in the optimization of nanoparticle-based T1 MRI contrast agents. It is important to characterize the potential toxicity of nanomaterials that are intended for use in biomedical applications. Thus, I evaluated the in vivo biodistribution and acute toxicity in rats of gold nanostars functionalized with DNA. As expected for nanoparticles of this size (˜50 nm) and surface charge (negative), the primary clearance mechanism was through the liver and spleen. Importantly, even at the highest dose, no signs of acute toxicity were observed based on hematology, clinical chemistry, and histology, indicating that DNA-coated gold nanostars are highly biocompatible. Additionally, I exploited the high contrast of gold in electron microscopy to track the fate of the nanoconstructs within organs ex vivo. In the liver, the nanoconstructs were sequestered in lysosomes of Kupffer cells. The electron microscopy analysis also indicated that the branched structure of the nanostars was intact even after 2 weeks in the liver, which is important for shape-dependent applications.

Cell biology, MRI and geometry: insight into a microscopic/macroscopic marriage.

PubMed

de Oliveira, Sérgio Almeida; Gowdak, Luís Henrique W; Buckberg, Gerald; Krieger, José Eduardo

2006-04-01

The concept of cell therapy as an adjunctive therapy to myocardial surgical revascularization for patients with severe coronary artery disease is illustrated by two case reports of ischemic cardiac disease that were unsuitable for revascularization by coronary grafting. The potential interaction of cell therapy, magnetic resonance imaging (MRI) of viability, and left ventricle (LV) restoration is described. Each patient had an ejection fraction below 30%, a relatively conical heart, and MRI gadolinium scan showing predominantly viable muscle. Intramyocardial injections of autologous bone marrow-derived cells (BMC) were performed along with either incomplete coronary artery bypass grafting (CABG) (to mother regions) or with transmyocardial laser revascularization (TMLR). An improvement in contractile function was seen at 6-12-month intervals after the procedure. The implications of possible underlying mechanisms of improvement in both myocardial perfusion and contractility suggest the striking importance of both micro- and macroenvironment for any cell-based therapeutic strategy. These observations imply that the interaction of cell biology, viability by MRI and geometry may be important in the future, as geometry can be restored surgically, and the new architectural form may develop enhanced function if it contains viable tissue and cell-based treatment can be delivered.

Catheter tracking using continuous radial MRI.

PubMed

Rasche, V; Holz, D; Köhler, J; Proksa, R; Röschmann, P

1997-06-01

The guidance of minimally invasive procedures may become a very important future application of MRI. The guidance of interventions requires images of the anatomy as well as the information of the position of invasive devices used. This paper introduces continuous radial MRI for the simultaneous acquisition of the anatomic MR image and the position of one or more small RF-coils (mu-coils), which can be mounted on invasive devices such as catheters or biopsy needles. This approach allows the in-plane tracking of an invasive device without any prolongation of the overall acquisition time. The extension to three-dimensional position tracking is described. Phantom studies are presented demonstrating the capability of this technique for real-time automatic adjustment of the slice position to the current catheter position with a temporal resolution of 100 ms. Simultaneously the in-plane catheter position is depicted in the actually acquired MR image during continuous scanning.

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

PubMed

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

2012-04-01

Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based (1)H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a (19)F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on (1)H-MRI scans. Twenty percent of cells labeled with the (19)F agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T(2)- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. Copyright © 2011 Elsevier Ltd. All rights reserved.

19F spin-lattice relaxation of perfluoropolyethers: Dependence on temperature and magnetic field strength (7.0-14.1 T)

NASA Astrophysics Data System (ADS)

Kadayakkara, Deepak K.; Damodaran, Krishnan; Hitchens, T. Kevin; Bulte, Jeff W. M.; Ahrens, Eric T.

2014-05-01

Fluorine (19F) MRI of perfluorocarbon-labeled cells has become a powerful technique to track the migration and accumulation of cells in living organisms. It is common to label cells for 19F MRI with nanoemulsions of perfluoropolyethers that contain a large number of chemically equivalent fluorine atoms. Understanding the mechanisms of 19F nuclear relaxation, and in particular the spin-lattice relaxation of these molecules, is critical to improving experimental sensitivity. To date, the temperature and magnetic field strength dependence of spin-lattice relaxation rate constant (R1) for perfluoropolyethers has not been described in detail. In this study, we evaluated the R1 of linear perfluoropolyether (PFPE) and cyclic perfluoro-15-crown-5 ether (PCE) at three magnetic field strengths (7.0, 9.4, and 14.1 T) and at temperatures ranging from 256-323 K. Our results show that R1 of perfluoropolyethers is dominated by dipole-dipole interactions and chemical shift anisotropy. R1 increased with magnetic field strength for both PCE and PFPE. In the temperature range studied, PCE was in the fast motion regime (ωτc < 1) at all field strengths, but for PFPE, R1 passed through a maximum, from which the rotational correlation time was estimated. The importance of these measurements for the rational design of new 19F MRI agents and methods is discussed.

19F Spin-lattice Relaxation of Perfluoropolyethers: Dependence on Temperature and Magnetic Field Strength (7.0-14.1T)

PubMed Central

Kadayakkara, Deepak K.; Damodaran, Krishnan; Hitchens, T. Kevin; Bulte, Jeff W.M.; Ahrens, Eric T.

2014-01-01

Fluorine (19F) MRI of perfluorocarbon labeled cells has become a powerful technique to track the migration and accumulation of cells in living organisms. It is common to label cells for 19F MRI with nanoemulsions of perfluoropolyethers that contain a large number of chemically equivalent fluorine atoms. Understanding the mechanisms of 19F nuclear relaxation, and in particular the spin-lattice relaxation of these molecules, is critical to improving experimental sensitivity. To date, the temperature and magnetic field strength dependence of spin-lattice relaxation rate constant (R1) for perfluoropolyethers has not been described in detail. In this study, we evaluated R1 of linear perfluoropolyether (PFPE) and cyclic perfluoro-15-crown-5 ether (PCE) at three magnetic field strengths (7.0, 9.4, and 14.1 T) and at temperatures ranging from 256-323K. Our results show that R1 of perfluoropolyethers is dominated by dipole-dipole interactions and chemical shift anisotropy. R1 increased with magnetic field strength for both PCE and PFPE. In the temperature range studied, PCE was in the fast motion regime (ωτc < 1) at all field strengths, but for PFPE, R1 passed through a maximum, from which the rotational correlation time was estimated. The importance of these measurements for the rational design of new 19F MRI agents and methods is discussed. PMID:24594752

MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury.

PubMed

Li, Lian; Chopp, Michael; Ding, Guang Liang; Qu, Chang Sheng; Li, Qing Jiang; Lu, Mei; Wang, Shiyang; Nejad-Davarani, Siamak P; Mahmood, Asim; Jiang, Quan

2012-11-01

Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 × 10(6) hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood-brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.

A Simulation Tool for Dynamic Contrast Enhanced MRI

PubMed Central

Mauconduit, Franck; Christen, Thomas; Barbier, Emmanuel Luc

2013-01-01

The quantification of bolus-tracking MRI techniques remains challenging. The acquisition usually relies on one contrast and the analysis on a simplified model of the various phenomena that arise within a voxel, leading to inaccurate perfusion estimates. To evaluate how simplifications in the interstitial model impact perfusion estimates, we propose a numerical tool to simulate the MR signal provided by a dynamic contrast enhanced (DCE) MRI experiment. Our model encompasses the intrinsic and relaxations, the magnetic field perturbations induced by susceptibility interfaces (vessels and cells), the diffusion of the water protons, the blood flow, the permeability of the vessel wall to the the contrast agent (CA) and the constrained diffusion of the CA within the voxel. The blood compartment is modeled as a uniform compartment. The different blocks of the simulation are validated and compared to classical models. The impact of the CA diffusivity on the permeability and blood volume estimates is evaluated. Simulations demonstrate that the CA diffusivity slightly impacts the permeability estimates ( for classical blood flow and CA diffusion). The effect of long echo times is investigated. Simulations show that DCE-MRI performed with an echo time may already lead to significant underestimation of the blood volume (up to 30% lower for brain tumor permeability values). The potential and the versatility of the proposed implementation are evaluated by running the simulation with realistic vascular geometry obtained from two photons microscopy and with impermeable cells in the extravascular environment. In conclusion, the proposed simulation tool describes DCE-MRI experiments and may be used to evaluate and optimize acquisition and processing strategies. PMID:23516414

Two decades of dendrimers as versatile MRI agents: a tale with and without metals.

PubMed

McMahon, Michael T; Bulte, Jeff W M

2018-05-01

Dendrimers or dendritic polymers are a class of compounds with great potential for nanomedical use. Some of their properties, including their rigidity, low polydispersity and the ease with which their surfaces can be modified make them particularly well suited for use as MRI diagnostic or theranostic agents. For the past 20 years, researchers have recognized this potential and refined dendrimer formulations to optimize these nanocarriers for a host of MRI applications, including blood pool imaging agents, lymph node imaging agents, tumor-targeted theranostic agents and cell tracking agents. This review summarizes the various types of dendrimers according to the type of MR contrast they can provide. This includes the metallic T 1 , T 2 and paraCEST imaging agents, and the non-metallic diaCEST and fluorinated ( 19 F) heteronuclear imaging agents. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanomaterials and Implants. © 2017 Wiley Periodicals, Inc.

Neural and Behavioral Sequelae of Blast-Related Traumatic Brain Injury

DTIC Science & Technology

2012-09-01

fMRI, DTI , cognition 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a...techniques [task-activated functional MRI (fMRI) and diffusion tensor imaging ( DTI )] to gain a comprehensive understanding of the neural changes...orthopedic injuries. We accomplished this goal by conducting advanced neuroimaging (task-activated fMRI and DTI fiber tracking) and neurobehavioral

Decoding brain cancer dynamics: a quantitative histogram-based approach using temporal MRI

NASA Astrophysics Data System (ADS)

Zhou, Mu; Hall, Lawrence O.; Goldgof, Dmitry B.; Russo, Robin; Gillies, Robert J.; Gatenby, Robert A.

2015-03-01

Brain tumor heterogeneity remains a challenge for probing brain cancer evolutionary dynamics. In light of evolution, it is a priority to inspect the cancer system from a time-domain perspective since it explicitly tracks the dynamics of cancer variations. In this paper, we study the problem of exploring brain tumor heterogeneity from temporal clinical magnetic resonance imaging (MRI) data. Our goal is to discover evidence-based knowledge from such temporal imaging data, where multiple clinical MRI scans from Glioblastoma multiforme (GBM) patients are generated during therapy. In particular, we propose a quantitative histogram-based approach that builds a prediction model to measure the difference in histograms obtained from pre- and post-treatment. The study could significantly assist radiologists by providing a metric to identify distinctive patterns within each tumor, which is crucial for the goal of providing patient-specific treatments. We examine the proposed approach for a practical application - clinical survival group prediction. Experimental results show that our approach achieved 90.91% accuracy.

Quantifying diffusion MRI tractography of the corticospinal tract in brain tumors with deterministic and probabilistic methods☆

PubMed Central

Bucci, Monica; Mandelli, Maria Luisa; Berman, Jeffrey I.; Amirbekian, Bagrat; Nguyen, Christopher; Berger, Mitchel S.; Henry, Roland G.

2013-01-01

Introduction Diffusion MRI tractography has been increasingly used to delineate white matter pathways in vivo for which the leading clinical application is presurgical mapping of eloquent regions. However, there is rare opportunity to quantify the accuracy or sensitivity of these approaches to delineate white matter fiber pathways in vivo due to the lack of a gold standard. Intraoperative electrical stimulation (IES) provides a gold standard for the location and existence of functional motor pathways that can be used to determine the accuracy and sensitivity of fiber tracking algorithms. In this study we used intraoperative stimulation from brain tumor patients as a gold standard to estimate the sensitivity and accuracy of diffusion tensor MRI (DTI) and q-ball models of diffusion with deterministic and probabilistic fiber tracking algorithms for delineation of motor pathways. Methods We used preoperative high angular resolution diffusion MRI (HARDI) data (55 directions, b = 2000 s/mm2) acquired in a clinically feasible time frame from 12 patients who underwent a craniotomy for resection of a cerebral glioma. The corticospinal fiber tracts were delineated with DTI and q-ball models using deterministic and probabilistic algorithms. We used cortical and white matter IES sites as a gold standard for the presence and location of functional motor pathways. Sensitivity was defined as the true positive rate of delineating fiber pathways based on cortical IES stimulation sites. For accuracy and precision of the course of the fiber tracts, we measured the distance between the subcortical stimulation sites and the tractography result. Positive predictive rate of the delineated tracts was assessed by comparison of subcortical IES motor function (upper extremity, lower extremity, face) with the connection of the tractography pathway in the motor cortex. Results We obtained 21 cortical and 8 subcortical IES sites from intraoperative mapping of motor pathways. Probabilistic q-ball had the best sensitivity (79%) as determined from cortical IES compared to deterministic q-ball (50%), probabilistic DTI (36%), and deterministic DTI (10%). The sensitivity using the q-ball algorithm (65%) was significantly higher than using DTI (23%) (p < 0.001) and the probabilistic algorithms (58%) were more sensitive than deterministic approaches (30%) (p = 0.003). Probabilistic q-ball fiber tracks had the smallest offset to the subcortical stimulation sites. The offsets between diffusion fiber tracks and subcortical IES sites were increased significantly for those cases where the diffusion fiber tracks were visibly thinner than expected. There was perfect concordance between the subcortical IES function (e.g. hand stimulation) and the cortical connection of the nearest diffusion fiber track (e.g. upper extremity cortex). Discussion This study highlights the tremendous utility of intraoperative stimulation sites to provide a gold standard from which to evaluate diffusion MRI fiber tracking methods and has provided an object standard for evaluation of different diffusion models and approaches to fiber tracking. The probabilistic q-ball fiber tractography was significantly better than DTI methods in terms of sensitivity and accuracy of the course through the white matter. The commonly used DTI fiber tracking approach was shown to have very poor sensitivity (as low as 10% for deterministic DTI fiber tracking) for delineation of the lateral aspects of the corticospinal tract in our study. Effects of the tumor/edema resulted in significantly larger offsets between the subcortical IES and the preoperative fiber tracks. The provided data show that probabilistic HARDI tractography is the most objective and reproducible analysis but given the small sample and number of stimulation points a generalization about our results should be given with caution. Indeed our results inform the capabilities of preoperative diffusion fiber tracking and indicate that such data should be used carefully when making pre-surgical and intra-operative management decisions. PMID:24273719

Systematic investigations of intense convective precipitation events on European scale based on radar- and lightning-cell tracking

NASA Astrophysics Data System (ADS)

Tüchler, Lukas; Meyer, Vera

2013-04-01

The new radar-data and lightning-data based automatic cell identification, tracking and nowcasting tool A-TNT (Austrian Thunderstorm Nowcasting Tool), which has been developed at ZAMG, has been applied to investigate the appearance of thunderstorms at Europe scale. Based on the ec-TRAM-method [1], the algorithm identifies and monitors regions of intense precipitation and lightning activity separately by analyzing sequential two-dimensional intensity maps of radar precipitation rate or lightning densities, respectively. Each data source is processed by a stand-alone identification, tracking and nowcasting procedure. The two tracking results are combined to a "main" cell in a final step. This approach allows that the output derived from the two data sources complement each other giving a more comprehensive picture about the current storm situation. So it is possible to distinguish between pure precipitation cells and thunderstorms, to observe regions, where one data source is not or poorly available, and to compensate for occasional data failures. Consequently, the combined cell-tracks are expected to be more consistent and the cell-tracking more robust. Input data for radar-cell tracking on European Scale is the OPERA radar-composite, which is provided every 15 minutes on a 2 km x 2 km grid, indicating the location and intensity of precipitation over Europe. For the lightning-cell tracking, the lightning-detection data of the EUCLID network is mapped on the OPERA grid. Every five minutes, flash density maps with recorded strokes are created and analyzed. This study will present a detailed investigation of the quality of the identification and tracking results using radar and lightning data. The improvements concerning the robustness and reliability of the cell tracking achieved by combining both data sources will be shown. Analyses about cell tracks and selected storm parameters like frequency, longevity and area will give insight into occurrence, appearance and impact of different severe precipitation events. These studies are performed to support the project HAREN (Hazard Assessment based on Rainfall European Nowcasts, funded by the EC Directorate General for Humanitarian Aid and Civil Protection), which has the objective to improve warnings for hazards induced by precipitation at local scale all over Europe. REFERENCES: [1] Meyer, V. K., H. Höller, and H. D. Betz 2012: Automated thunderstorm tracking and nowcasting: utilization of three-dimensional lightning and radar data. Manuscript accepted for publication in ACPD.

In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis.

PubMed

Kirschbaum, Klara; Sonner, Jana K; Zeller, Matthias W; Deumelandt, Katrin; Bode, Julia; Sharma, Rakesh; Krüwel, Thomas; Fischer, Manuel; Hoffmann, Angelika; Costa da Silva, Milene; Muckenthaler, Martina U; Wick, Wolfgang; Tews, Björn; Chen, John W; Heiland, Sabine; Bendszus, Martin; Platten, Michael; Breckwoldt, Michael O

2016-11-15

Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood-brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood. In this study we used MRI to map inflammatory infiltrates using high-field MRI and fluorescently labeled cross-linked iron oxide nanoparticles for cell tracking. We confirmed nanoparticle uptake and MR detectability ex vivo. Using in vivo MRI, we identified extensive nanoparticle signal in the cerebellar white matter and circumscribed cortical gray matter lesions that developed during the disease course (4.6-fold increase of nanoparticle accumulation in EAE compared with healthy controls, P < 0.001). Nanoparticles showed good cellular specificity for innate immune cells in vivo, labeling activated microglia, infiltrating macrophages, and neutrophils, whereas there was only sparse uptake by adaptive immune cells. Importantly, nanoparticle signal correlated better with clinical disease than conventional gadolinium (Gd) imaging (r, 0.83 for nanoparticles vs. 0.71 for Gd-imaging, P < 0.001). We validated our approach using the Food and Drug Administration-approved iron oxide nanoparticle ferumoxytol. Our results show that noninvasive molecular imaging of innate immune responses can serve as an imaging biomarker of disease activity in autoimmune-mediated neuroinflammation with potential clinical applications in a wide range of inflammatory diseases.

Multivalent Protein Polymer MRI Contrast Agents: Controlling Relaxivity via Modulation of Amino Acid Sequence

PubMed Central

Karfeld-Sulzer, Lindsay S.; Waters, Emily A.; Davis, Nicolynn E.; Meade, Thomas J.; Barron, Annelise E.

2010-01-01

Magnetic Resonance Imaging (MRI) is a noninvasive imaging modality with high spatial and temporal resolution. Contrast agents (CAs) are frequently used to increase the contrast between tissues of interest. To increase the effectiveness of MR agents, small molecule CAs have been attached to macromolecules. We have created a family of biodegradable, macromolecular CAs based on protein polymers, allowing control over the CA properties. The protein polymers are monodisperse, random coil, and contain evenly spaced lysines that serve as reactive sites for Gd(III) chelates. The exact sequence and length of the protein can be specified, enabling controlled variation in lysine spacing and molecular weight. Relaxivity could be modulated by changing protein polymer length and lysine spacing. Relaxivities of up to ∼14 mM-1s-1 per Gd(III) and ∼461 mM-1s-1 per conjugate were observed. These CAs are biodegradable by incubation with plasmin, such that they can be easily excreted after use. They do not reduce cell viability, a prerequisite for future in vivo studies. The protein polymer CAs can be customized for different clinical diagnostic applications, including biomaterial tracking, as a balanced agent with high relaxivity and appropriate molar mass. PMID:20420441

High quality polyacrylic acid modified multifunction luminescent nanorods for tri-modality bioimaging, in vivo long-lasting tracking and biodistribution

NASA Astrophysics Data System (ADS)

Yi, Zhigao; Lu, Wei; Liu, Hongrong; Zeng, Songjun

2014-12-01

Polyacrylic acid (PAA) modified NaYF4:Gd/Yb/Er upconversion nanorods (denoted as PAA-UCNRs) are demonstrated for tri-modal upconversion (UC) optical, computed X-ray tomography (CT), and magnetic resonance imaging (MRI). The hydrophilic PAA-UCNRs were obtained from hydrophobic oleic acid (OA) capped UCNRs (denoted as OA-UCNRs) using a ligand exchange method. The as-prepared UCNRs with a hexagonal phase structure present high monodispersity. These PAA-UCNRs are successfully used as ideal probes for in vivo UC luminescence bioimaging and synergistic X-ray and UC bioimaging. Moreover, X-ray CT imaging reveals that PAA-UCNRs can act as contrast agents for improved detection of the liver and spleen. In addition, a significant signal enhancement in the liver is observed in in vivo MRI, indicating that PAA-UCNRs are ideal T1-weighted MRI agents. More importantly, in vivo long-term tracking based on these PAA-UCNRs in the live mice and the corresponding ex vivo bioimaging of isolated organs also verify the translocation of PAA-UCNRs from the liver to the spleen, and the observed intense UC signals from the feces reveal the biliary excretion mechanism of these UCNRs. These findings contribute to understanding of the translocation and potential route for excretion of PAA-UCNRs, which can provide an important guide for the diagnosis and detection of diseases based on these UCNRs.Polyacrylic acid (PAA) modified NaYF4:Gd/Yb/Er upconversion nanorods (denoted as PAA-UCNRs) are demonstrated for tri-modal upconversion (UC) optical, computed X-ray tomography (CT), and magnetic resonance imaging (MRI). The hydrophilic PAA-UCNRs were obtained from hydrophobic oleic acid (OA) capped UCNRs (denoted as OA-UCNRs) using a ligand exchange method. The as-prepared UCNRs with a hexagonal phase structure present high monodispersity. These PAA-UCNRs are successfully used as ideal probes for in vivo UC luminescence bioimaging and synergistic X-ray and UC bioimaging. Moreover, X-ray CT imaging reveals that PAA-UCNRs can act as contrast agents for improved detection of the liver and spleen. In addition, a significant signal enhancement in the liver is observed in in vivo MRI, indicating that PAA-UCNRs are ideal T1-weighted MRI agents. More importantly, in vivo long-term tracking based on these PAA-UCNRs in the live mice and the corresponding ex vivo bioimaging of isolated organs also verify the translocation of PAA-UCNRs from the liver to the spleen, and the observed intense UC signals from the feces reveal the biliary excretion mechanism of these UCNRs. These findings contribute to understanding of the translocation and potential route for excretion of PAA-UCNRs, which can provide an important guide for the diagnosis and detection of diseases based on these UCNRs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05161k

In-Vivo Imaging of Cell Migration Using Contrast Enhanced MRI and SVM Based Post-Processing.

PubMed

Weis, Christian; Hess, Andreas; Budinsky, Lubos; Fabry, Ben

2015-01-01

The migration of cells within a living organism can be observed with magnetic resonance imaging (MRI) in combination with iron oxide nanoparticles as an intracellular contrast agent. This method, however, suffers from low sensitivity and specificty. Here, we developed a quantitative non-invasive in-vivo cell localization method using contrast enhanced multiparametric MRI and support vector machines (SVM) based post-processing. Imaging phantoms consisting of agarose with compartments containing different concentrations of cancer cells labeled with iron oxide nanoparticles were used to train and evaluate the SVM for cell localization. From the magnitude and phase data acquired with a series of T2*-weighted gradient-echo scans at different echo-times, we extracted features that are characteristic for the presence of superparamagnetic nanoparticles, in particular hyper- and hypointensities, relaxation rates, short-range phase perturbations, and perturbation dynamics. High detection quality was achieved by SVM analysis of the multiparametric feature-space. The in-vivo applicability was validated in animal studies. The SVM detected the presence of iron oxide nanoparticles in the imaging phantoms with high specificity and sensitivity with a detection limit of 30 labeled cells per mm3, corresponding to 19 μM of iron oxide. As proof-of-concept, we applied the method to follow the migration of labeled cancer cells injected in rats. The combination of iron oxide labeled cells, multiparametric MRI and a SVM based post processing provides high spatial resolution, specificity, and sensitivity, and is therefore suitable for non-invasive in-vivo cell detection and cell migration studies over prolonged time periods.

Value of speckle tracking for the assessment of right ventricular function in patients operated on for tetralogy of fallot. Comparison with magnetic resonance imaging.

PubMed

Bernard, Yvette; Morel, Mathilde; Descotes-Genon, Vincent; Jehl, Jerome; Meneveau, Nicolas; Schiele, Francois

2014-04-01

Right ventricular (RV) function is a major prognostic factor in patients (pts) with operated tetralogy of Fallot (TOF). We compared the results of RV speckle tracking (two-dimensional [2D] strain) with those of magnetic resonance imaging (MRI) in this setting. At transthoracic echocardiogram (echo), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), velocity of S-wave at tricuspid annulus with tissue Doppler, and 2D strain (longitudinal maximal systolic strain) were recorded. Their results were compared to RV indexed end-diastolic volume (EDV), indexed end-systolic volume (ESV), and RV ejection fraction (EF) at MRI. Twenty-two pts (16 M) aged 11-62 years (mean 23.2 ± 10.8) were included. Parameters of RV systolic function were as follows: RVFAC = 40 ± 10%, TAPSE = 18 ± 4 mm, S-wave = 10 ± 0.2 cm/sec, and RV EF at MRI = 43 ± 11%. Global RV systolic strain was -15.5 ± 4.2%, free wall strain was -15.1 ± 6.3%, and septal strain was -15.8 ± 3.8% on average for the whole group. Echo indexed RV end-diastolic area correlated with EDV at MRI (r = 0.73), as well as echo indexed RV end-systolic area and ESV at MRI (r = 0.71). Global RV 2D strain correlated well with RV EF at MRI: r = 0.68; P < 0.05, and with ESV at MRI: r = 0.63. Feasibility, intra- and inter-observer reproducibility of 2D strain were adequate. Speckle tracking is a promising method to estimate RV systolic function in pts operated on for TOF. © 2013, Wiley Periodicals, Inc.

SU-E-J-168: Automated Pancreas Segmentation Based On Dynamic MRI

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

Gou, S; Rapacchi, S; Hu, P

2014-06-01

Purpose: MRI guided radiotherapy is particularly attractive for abdominal targets with low CT contrast. To fully utilize this modality for pancreas tracking, automated segmentation tools are needed. A hybrid gradient, region growth and shape constraint (hGReS) method to segment 2D upper abdominal dynamic MRI is developed for this purpose. Methods: 2D coronal dynamic MR images of 2 healthy volunteers were acquired with a frame rate of 5 f/second. The regions of interest (ROIs) included the liver, pancreas and stomach. The first frame was used as the source where the centers of the ROIs were annotated. These center locations were propagatedmore » to the next dynamic MRI frame. 4-neighborhood region transfer growth was performed from these initial seeds for rough segmentation. To improve the results, gradient, edge and shape constraints were applied to the ROIs before final refinement using morphological operations. Results from hGReS and 3 other automated segmentation methods using edge detection, region growth and level set were compared to manual contouring. Results: For the first patient, hGReS resulted in the organ segmentation accuracy as measure by the Dices index (0.77) for the pancreas. The accuracy was slightly superior to the level set method (0.72), and both are significantly more accurate than the edge detection (0.53) and region growth methods (0.42). For the second healthy volunteer, hGReS reliably segmented the pancreatic region, achieving a Dices index of 0.82, 0.92 and 0.93 for the pancreas, stomach and liver, respectively, comparing to manual segmentation. Motion trajectories derived from the hGReS, level set and manual segmentation methods showed high correlation to respiratory motion calculated using a lung blood vessel as the reference while the other two methods showed substantial motion tracking errors. hGReS was 10 times faster than level set. Conclusion: We have shown the feasibility of automated segmentation of the pancreas anatomy based on dynamic MRI.« less

A PET/CT-Based Strategy Is a Stronger Predictor of Survival Than a Standard Imaging Strategy in Patients with Head and Neck Squamous Cell Carcinoma.

PubMed

Rohde, Max; Nielsen, Anne L; Pareek, Manan; Johansen, Jørgen; Sørensen, Jens A; Diaz, Anabel; Nielsen, Mie K; Christiansen, Janus M; Asmussen, Jon T; Nguyen, Nina; Gerke, Oke; Thomassen, Anders; Alavi, Abass; Høilund-Carlsen, Poul Flemming; Godballe, Christian

2018-04-01

Our purpose was to examine whether staging of head and neck squamous cell carcinoma (HNSCC) by upfront 18 F-FDG PET/CT (i.e., on the day of biopsy and before the biopsy) discriminates survival better than the traditional imaging strategies based on chest x-ray plus head and neck MRI (CXR/MRI) or chest CT plus head and neck MRI (CCT/MRI). Methods: We performed a masked prospective cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were recruited from Odense University Hospital from September 2013 to March 2016. All patients underwent CXR/MRI, CCT/MRI, and PET/CT on the same day. Tumors were categorized as localized (stages I and II), locally advanced (stages III and IVB), or metastatic (stage IVC). Discriminative ability for each imaging modality with respect to HNSCC staging were compared using Kaplan-Meier analysis, Cox proportional hazards regression with the Harrell C-index, and net reclassification improvement. Results: In total, 307 patients with histologically verified HNSCC were included. Use of PET/CT significantly altered the stratification of tumor stage when compared with either CXR/MRI or CCT/MRI (χ 2 , P < 0.001 for both). Cancer stages based on PET/CT, but not CXR/MRI or CCT/MRI, were associated with significant differences in mortality risk on Kaplan-Meier analyses ( P ≤ 0.002 for all PET/CT-based comparisons). Furthermore, overall discriminative ability was significantly greater for PET/CT (C-index, 0.712) than for CXR/MRI (C-index, 0.675; P = 0.04) or CCT/MRI (C-index, 0.657; P = 0.02). Finally, PET/CT was significantly associated with a positive net reclassification improvement when compared with CXR/MRI (0.184, P = 0.03) but not CCT/MRI (0.094%, P = 0.31). Conclusion: Tumor stages determined by PET/CT were associated with more distinct prognostic properties in terms of survival than those determined by standard imaging strategies. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Segmentation of Nerve Bundles and Ganglia in Spine MRI Using Particle Filters

PubMed Central

Dalca, Adrian; Danagoulian, Giovanna; Kikinis, Ron; Schmidt, Ehud; Golland, Polina

2011-01-01

Automatic segmentation of spinal nerve bundles that originate within the dural sac and exit the spinal canal is important for diagnosis and surgical planning. The variability in intensity, contrast, shape and direction of nerves seen in high resolution myelographic MR images makes segmentation a challenging task. In this paper, we present an automatic tracking method for nerve segmentation based on particle filters. We develop a novel approach to particle representation and dynamics, based on Bézier splines. Moreover, we introduce a robust image likelihood model that enables delineation of nerve bundles and ganglia from the surrounding anatomical structures. We demonstrate accurate and fast nerve tracking and compare it to expert manual segmentation. PMID:22003741

Segmentation of nerve bundles and ganglia in spine MRI using particle filters.

PubMed

Dalca, Adrian; Danagoulian, Giovanna; Kikinis, Ron; Schmidt, Ehud; Golland, Polina

2011-01-01

Automatic segmentation of spinal nerve bundles that originate within the dural sac and exit the spinal canal is important for diagnosis and surgical planning. The variability in intensity, contrast, shape and direction of nerves seen in high resolution myelographic MR images makes segmentation a challenging task. In this paper, we present an automatic tracking method for nerve segmentation based on particle filters. We develop a novel approach to particle representation and dynamics, based on Bézier splines. Moreover, we introduce a robust image likelihood model that enables delineation of nerve bundles and ganglia from the surrounding anatomical structures. We demonstrate accurate and fast nerve tracking and compare it to expert manual segmentation.

Sub-pixel localisation of passive micro-coil fiducial markers in interventional MRI.

PubMed

Rea, Marc; McRobbie, Donald; Elhawary, Haytham; Tse, Zion T H; Lamperth, Michael; Young, Ian

2009-04-01

Electromechanical devices enable increased accuracy in surgical procedures, and the recent development of MRI-compatible mechatronics permits the use of MRI for real-time image guidance. Integrated imaging of resonant micro-coil fiducials provides an accurate method of tracking devices in a scanner with increased flexibility compared to gradient tracking. Here we report on the ability of ten different image-processing algorithms to track micro-coil fiducials with sub-pixel accuracy. Five algorithms: maximum pixel, barycentric weighting, linear interpolation, quadratic fitting and Gaussian fitting were applied both directly to the pixel intensity matrix and to the cross-correlation matrix obtained by 2D convolution with a reference image. Using images of a 3 mm fiducial marker and a pixel size of 1.1 mm, intensity linear interpolation, which calculates the position of the fiducial centre by interpolating the pixel data to find the fiducial edges, was found to give the best performance for minimal computing power; a maximum error of 0.22 mm was observed in fiducial localisation for displacements up to 40 mm. The inherent standard deviation of fiducial localisation was 0.04 mm. This work enables greater accuracy to be achieved in passive fiducial tracking.

Multimode intravascular RF coil for MRI-guided interventions.

PubMed

Kurpad, Krishna N; Unal, Orhan

2011-04-01

To demonstrate the feasibility of using a single intravascular radiofrequency (RF) probe connected to the external magnetic resonance imaging (MRI) system via a single coaxial cable to perform active tip tracking and catheter visualization and high signal-to-noise ratio (SNR) intravascular imaging. A multimode intravascular RF coil was constructed on a 6F balloon catheter and interfaced to a 1.5T MRI scanner via a decoupling circuit. Bench measurements of coil impedances were followed by imaging experiments in saline and phantoms. The multimode coil behaves as an inductively coupled transmit coil. The forward-looking capability of 6 mm was measured. A greater than 3-fold increase in SNR compared to conventional imaging using optimized external coil was demonstrated. Simultaneous active tip tracking and catheter visualization was demonstrated. It is feasible to perform 1) active tip tracking, 2) catheter visualization, and 3) high SNR imaging using a single multimode intravascular RF coil that is connected to the external system via a single coaxial cable. Copyright © 2011 Wiley-Liss, Inc.

Multi-mode Intravascular RF Coil for MRI-guided Interventions

PubMed Central

Kurpad, Krishna N.; Unal, Orhan

2011-01-01

Purpose To demonstrate the feasibility of using a single intravascular RF probe connected to the external MRI system via a single coaxial cable to perform active tip tracking and catheter visualization, and high SNR intravascular imaging. Materials and Methods A multi-mode intravascular RF coil was constructed on a 6F balloon catheter and interfaced to a 1.5T MRI scanner via a decoupling circuit. Bench measurements of coil impedances were followed by imaging experiments in saline and phantoms. Results The multi-mode coil behaves as an inductively-coupled transmit coil. Forward looking capability of 6mm is measured. Greater than 3-fold increase in SNR compared to conventional imaging using optimized external coil is demonstrated. Simultaneous active tip tracking and catheter visualization is demonstrated. Conclusions It is feasible to perform 1) active tip tracking, 2) catheter visualization, and 3) high SNR imaging using a single multi-mode intravascular RF coil that is connected to the external system via a single coaxial cable. PMID:21448969

Real-Time Correction By Optical Tracking with Integrated Geometric Distortion Correction for Reducing Motion Artifacts in fMRI

NASA Astrophysics Data System (ADS)

Rotenberg, David J.

Artifacts caused by head motion are a substantial source of error in fMRI that limits its use in neuroscience research and clinical settings. Real-time scan-plane correction by optical tracking has been shown to correct slice misalignment and non-linear spin-history artifacts, however residual artifacts due to dynamic magnetic field non-uniformity may remain in the data. A recently developed correction technique, PLACE, can correct for absolute geometric distortion using the complex image data from two EPI images, with slightly shifted k-space trajectories. We present a correction approach that integrates PLACE into a real-time scan-plane update system by optical tracking, applied to a tissue-equivalent phantom undergoing complex motion and an fMRI finger tapping experiment with overt head motion to induce dynamic field non-uniformity. Experiments suggest that including volume by volume geometric distortion correction by PLACE can suppress dynamic geometric distortion artifacts in a phantom and in vivo and provide more robust activation maps.

A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.

PubMed

Alberti, Diego; Protti, Nicoletta; Toppino, Antonio; Deagostino, Annamaria; Lanzardo, Stefania; Bortolussi, Silva; Altieri, Saverio; Voena, Claudia; Chiarle, Roberto; Geninatti Crich, Simonetta; Aime, Silvio

2015-04-01

This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation. Copyright © 2015 Elsevier Inc. All rights reserved.

[Functional neuro-navigation and intraoperative magnetic resonance imaging for the resection of gliomas involving eloquent language structures].

PubMed

Chen, Xiao-lei; Xu, Bai-nan; Wang, Fei; Meng, Xiang-hui; Zhang, Jun; Jiang, Jin-li; Yu, Xin-guang; Zhou, Ding-biao

2011-08-01

To explore the clinical value of functional neuro-navigation and high-field-strength intraoperative magnetic resonance imaging (iMRI) for the resection of intracerebral gliomas involving eloquent language structures. From April 2009 to April 2010, 48 patients with intracerebral gliomas involving eloquent language structures, were operated with functional neuro-navigation and iMRI. Blood oxygen level dependent functional MRI (BOLD-fMRI) was used to depict both Broca and Wernicke cortex, while diffusion tensor imaging (DTI) based fiber tracking was used to delineate arcuate fasciculus. The reconstructed language structures were integrated into a navigation system, so that intra-operative microscopic-based functional neuro-navigation could be achieved. iMRI was used to update the images for both language structures and residual tumors. All patients were evaluated for language function pre-operatively and post-operatively upon short-term and long-term follow-up. In all patients, functional neuro-navigation and iMRI were successfully achieved. In 38 cases (79.2%), gross total resection was accomplished, while in the rest 10 cases (20.8%), subtotal resection was achieved. Only 1 case (2.1%) developed long-term (more than 3 months) new language function deficits at post-operative follow-up. No peri-operative mortality was recorded. With functional neuro-navigation and iMRI, the eloquent structures for language can be precisely located, while the resection size can be accurately evaluated intra-operatively. This technique is safe and helpful for preservation of language function.

Intra-coil interactions in split gradient coils in a hybrid MRI-LINAC system

NASA Astrophysics Data System (ADS)

Tang, Fangfang; Freschi, Fabio; Sanchez Lopez, Hector; Repetto, Maurizio; Liu, Feng; Crozier, Stuart

2016-04-01

An MRI-LINAC system combines a magnetic resonance imaging (MRI) system with a medical linear accelerator (LINAC) to provide image-guided radiotherapy for targeting tumors in real-time. In an MRI-LINAC system, a set of split gradient coils is employed to produce orthogonal gradient fields for spatial signal encoding. Owing to this unconventional gradient configuration, eddy currents induced by switching gradient coils on and off may be of particular concern. It is expected that strong intra-coil interactions in the set will be present due to the constrained return paths, leading to potential degradation of the gradient field linearity and image distortion. In this study, a series of gradient coils with different track widths have been designed and analyzed to investigate the electromagnetic interactions between coils in a split gradient set. A driving current, with frequencies from 100 Hz to 10 kHz, was applied to study the inductive coupling effects with respect to conductor geometry and operating frequency. It was found that the eddy currents induced in the un-energized coils (hereby-referred to as passive coils) positively correlated with track width and frequency. The magnetic field induced by the eddy currents in the passive coils with wide tracks was several times larger than that induced by eddy currents in the cold shield of cryostat. The power loss in the passive coils increased with the track width. Therefore, intra-coil interactions should be included in the coil design and analysis process.

Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI

PubMed Central

Zhang, Yue; Udayakumar, Durga; Cai, Ling; Hu, Zeping; Kapur, Payal; Kho, Eun-Young; Pavía-Jiménez, Andrea; Fulkerson, Michael; de Leon, Alberto Diaz; Yuan, Qing; Dimitrov, Ivan E.; Ye, Jin; Mitsche, Matthew A.; Kim, Hyeonwoo; McDonald, Jeffrey G.; Madhuranthakam, Ananth J.; Dwivedi, Durgesh K.; Lenkinski, Robert E.; Cadeddu, Jeffrey A.; Margulis, Vitaly; Brugarolas, James; DeBerardinis, Ralph J.

2017-01-01

BACKGROUND. Dysregulated lipid and glucose metabolism in clear cell renal cell carcinoma (ccRCC) has been implicated in disease progression, and whole tumor tissue–based assessment of these changes is challenged by the tumor heterogeneity. We studied a noninvasive quantitative MRI method that predicts metabolic alterations in the whole tumor. METHODS. We applied Dixon-based MRI for in vivo quantification of lipid accumulation (fat fraction [FF]) in targeted regions of interest of 45 primary ccRCCs and correlated these MRI measures to mass spectrometry–based lipidomics and metabolomics of anatomically colocalized tissue samples isolated from the same tumor after surgery. RESULTS. In vivo tumor FF showed statistically significant (P < 0.0001) positive correlation with histologic fat content (Spearman correlation coefficient, ρ = 0.79), spectrometric triglycerides (ρ = 0.56) and cholesterol (ρ = 0.47); it showed negative correlation with free fatty acids (ρ = –0.44) and phospholipids (ρ = –0.65). We observed both inter- and intratumoral heterogeneity in lipid accumulation within the same tumor grade, whereas most aggressive tumors (International Society of Urological Pathology [ISUP] grade 4) exhibited reduced lipid accumulation. Cellular metabolites in tumors were altered compared with adjacent renal parenchyma. CONCLUSION. Our results support the use of noninvasive quantitative Dixon-based MRI as a biomarker of reprogrammed lipid metabolism in ccRCC, which may serve as a predictor of tumor aggressiveness before surgical intervention. FUNDING. NIH R01CA154475 (YZ, MF, PK, IP), NIH P50CA196516 (IP, JB, RJD, JAC, PK), Welch Foundation I-1832 (JY), and NIH P01HL020948 (JGM). PMID:28768909

Combined magnetic resonance imaging and ultrasound echography guidance for motion compensated HIFU interventions

NASA Astrophysics Data System (ADS)

Ries, Mario; de Senneville, Baudouin Denis; Regard, Yvan; Moonen, Chrit

2012-11-01

The objective of this study is to evaluate the feasibility to integrate ultrasound echography as an additional imaging modality for continuous target tracking, while performing simultaneously real-time MR- thermometry to guide a High Intensity Focused Ultrasound (HIFU) ablation. Experiments on a moving phantom were performed with MRI-guided HIFU during continuous ultrasound echography. Real-time US echography-based target tracking during MR-guided HIFU heating was performed with heated area dimensions similar to those obtained for a static target. The combination of both imaging modalities shows great potential for real-time beam steering and MR-thermometry.

Clinical feasibility and validation of 3D principal strain analysis from cine MRI: comparison to 2D strain by MRI and 3D speckle tracking echocardiography.

PubMed

Satriano, Alessandro; Heydari, Bobak; Narous, Mariam; Exner, Derek V; Mikami, Yoko; Attwood, Monica M; Tyberg, John V; Lydell, Carmen P; Howarth, Andrew G; Fine, Nowell M; White, James A

2017-12-01

Two-dimensional (2D) strain analysis is constrained by geometry-dependent reference directions of deformation (i.e. radial, circumferential, and longitudinal) following the assumption of cylindrical chamber architecture. Three-dimensional (3D) principal strain analysis may overcome such limitations by referencing intrinsic (i.e. principal) directions of deformation. This study aimed to demonstrate clinical feasibility of 3D principal strain analysis from routine 2D cine MRI with validation to strain from 2D tagged cine analysis and 3D speckle tracking echocardiography. Thirty-one patients undergoing cardiac MRI were studied. 3D strain was measured from routine, multi-planar 2D cine SSFP images using custom software designed to apply 4D deformation fields to 3D cardiac models to derive principal strain. Comparisons of strain estimates versus those by 2D tagged cine, 2D non-tagged cine (feature tracking), and 3D speckle tracking echocardiography (STE) were performed. Mean age was 51 ± 14 (36% female). Mean LV ejection fraction was 66 ± 10% (range 37-80%). 3D principal strain analysis was feasible in all subjects and showed high inter- and intra-observer reproducibility (ICC range 0.83-0.97 and 0.83-0.98, respectively-p < 0.001 for all directions). Strong correlations of minimum and maximum principal strain were respectively observed versus the following: 3D STE estimates of longitudinal (r = 0.81 and r = -0.64), circumferential (r = 0.76 and r = -0.58) and radial (r = -0.80 and r = 0.63) strain (p < 0.001 for all); 2D tagged cine estimates of longitudinal (r = 0.81 and r = -0.81), circumferential (r = 0.87 and r = -0.85), and radial (r = -0.76 and r = 0.81) strain (p < 0.0001 for all); and 2D cine (feature tracking) estimates of longitudinal (r = 0.85 and -0.83), circumferential (r = 0.88 and r = -0.87), and radial strain (r = -0.79 and r = 0.84, p < 0.0001 for all). 3D principal strain analysis is feasible using routine, multi-planar 2D cine MRI and shows high reproducibility with strong correlations to 2D conventional strain analysis and 3D STE-based analysis. Given its independence from geometry-related directions of deformation this technique may offer unique benefit for the detection and prognostication of myocardial disease, and warrants expanded investigation.

Gold nanoparticles for non-invasive cell tracking with CT imaging

NASA Astrophysics Data System (ADS)

Meir, Rinat; Betzer, Oshra; Barnoy, Eran; Motiei, Menachem; Popovtzer, Rachela

2018-02-01

Cell-based therapies use living cells with therapeutic traits to treat various diseases. This is a beneficial alternative for diseases that existing medicine cannot cure efficiently. However, inconsistent results in clinical trials are preventing the advancement and implementation of cell-based therapy. In order to explain such results, there is a need to discover the fate of the transplanted cells. To answer this need, we developed a technique for noninvasive in vivo cell tracking, which uses gold nanoparticles as contrast agents for CT imaging. Herein, we investigate the design principles of this technique for intramuscular transplantation of therapeutic cells. Longitudinal studies were performed, demonstrating the ability to track cells over long periods of time. As few as 500 cells could be detected and a way to quantify the number of cells visualized by CT was demonstrated. This cell-tracking technology has the potential to become an essential tool in pre-clinical studies as well as in clinical trials and advance cell therapy.

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin-avidin-specific binding.

PubMed

Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

2017-01-01

Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P <0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM -1 s -1 ) was observed compared to Magnevist ® (4.9 mM -1 s -1 ; P <0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor.

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

PubMed Central

Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

2017-01-01

Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM−1 s−1) was observed compared to Magnevist® (4.9 mM−1 s−1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. PMID:28765707

Magneto-reactance based detection of MnO nanoparticle-embedded Lewis lung carcinoma cells

NASA Astrophysics Data System (ADS)

Devkota, J.; Howell, M.; Mukherjee, P.; Srikanth, H.; Mohapatra, S.; Phan, M. H.

2015-05-01

We demonstrate the capacity of detecting magnetically weak manganese oxide (MnO) nanoparticles and the Lewis lung carcinoma (LLC) cancer cells that have taken up these nanoparticles using a novel biosensor based on the magneto-reactance (MX) effect of a soft ferromagnetic amorphous ribbon with a microhole-patterned surface. While the magnetic moment of the MnO nanoparticles is relatively small, and a magneto-impedance based sensor fails to detect them in solution (0.05 mg/ml manganese oxide lipid micellar nanoparticles) and inside cells at low concentrations (8.25 × 104 cells/ml), the detection of these nanoparticles and the LLC cells containing them is achieved with the MX-based sensor, which, respectively, reaches the detection sensitivity of ˜3.6% and 2.8% as compared to the blank cells. Since the MnO nanoparticles are a promising contrast agent for magnetic resonance imaging (MRI) of lung cells, the MX-based biosensing technique can be developed as a pre-detection method for MRI of lung cancer cells.

Graph-based retrospective 4D image construction from free-breathing MRI slice acquisitions

NASA Astrophysics Data System (ADS)

Tong, Yubing; Udupa, Jayaram K.; Ciesielski, Krzysztof C.; McDonough, Joseph M.; Mong, Andrew; Campbell, Robert M.

2014-03-01

4D or dynamic imaging of the thorax has many potential applications [1, 2]. CT and MRI offer sufficient speed to acquire motion information via 4D imaging. However they have different constraints and requirements. For both modalities both prospective and retrospective respiratory gating and tracking techniques have been developed [3, 4]. For pediatric imaging, x-ray radiation becomes a primary concern and MRI remains as the de facto choice. The pediatric subjects we deal with often suffer from extreme malformations of their chest wall, diaphragm, and/or spine, as such patient cooperation needed by some of the gating and tracking techniques are difficult to realize without causing patient discomfort. Moreover, we are interested in the mechanical function of their thorax in its natural form in tidal breathing. Therefore free-breathing MRI acquisition is the ideal modality of imaging for these patients. In our set up, for each coronal (or sagittal) slice position, slice images are acquired at a rate of about 200-300 ms/slice over several natural breathing cycles. This produces typically several thousands of slices which contain both the anatomic and dynamic information. However, it is not trivial to form a consistent and well defined 4D volume from these data. In this paper, we present a novel graph-based combinatorial optimization solution for constructing the best possible 4D scene from such data entirely in the digital domain. Our proposed method is purely image-based and does not need breath holding or any external surrogates or instruments to record respiratory motion or tidal volume. Both adult and children patients' data are used to illustrate the performance of the proposed method. Experimental results show that the reconstructed 4D scenes are smooth and consistent spatially and temporally, agreeing with known shape and motion of the lungs.

An automatic method of brain tumor segmentation from MRI volume based on the symmetry of brain and level set method

NASA Astrophysics Data System (ADS)

Li, Xiaobing; Qiu, Tianshuang; Lebonvallet, Stephane; Ruan, Su

2010-02-01

This paper presents a brain tumor segmentation method which automatically segments tumors from human brain MRI image volume. The presented model is based on the symmetry of human brain and level set method. Firstly, the midsagittal plane of an MRI volume is searched, the slices with potential tumor of the volume are checked out according to their symmetries, and an initial boundary of the tumor in the slice, in which the tumor is in the largest size, is determined meanwhile by watershed and morphological algorithms; Secondly, the level set method is applied to the initial boundary to drive the curve evolving and stopping to the appropriate tumor boundary; Lastly, the tumor boundary is projected one by one to its adjacent slices as initial boundaries through the volume for the whole tumor. The experiment results are compared with hand tracking of the expert and show relatively good accordance between both.

Design principles for noninvasive, longitudinal and quantitative cell tracking with nanoparticle-based CT imaging.

PubMed

Meir, Rinat; Betzer, Oshra; Motiei, Menachem; Kronfeld, Noam; Brodie, Chaya; Popovtzer, Rachela

2017-02-01

Contradictory results in clinical trials are preventing the advancement and implementation of cell-based therapy. To explain such results, there is a need to uncover the mystery regarding the fate of the transplanted cells. To answer this need, we developed a technique for noninvasive in vivo cell tracking, which uses gold nanoparticles as contrast agents for CT imaging. Herein, we investigate the design principles of this technique for intramuscular transplantation of therapeutic cells. Longitudinal studies were performed, displaying the ability to track cells over long periods of time. As few as 500 cells could be detected and a way to quantify the number of cells visualized by CT was demonstrated. Moreover, monitoring of cell functionality was demonstrated on a mouse model of Duchenne muscular dystrophy. This cell-tracking technology has the potential to become an essential tool in pre-clinical as well as clinical trials and to advance the future of cell therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Head-to-Head Comparison of Chest X-Ray/Head and Neck MRI, Chest CT/Head and Neck MRI, and 18F-FDG PET/CT for Detection of Distant Metastases and Synchronous Cancer in Oral, Pharyngeal, and Laryngeal Cancer.

PubMed

Rohde, Max; Nielsen, Anne L; Johansen, Jørgen; Sørensen, Jens A; Nguyen, Nina; Diaz, Anabel; Nielsen, Mie K; Asmussen, Jon T; Christiansen, Janus M; Gerke, Oke; Thomassen, Anders; Alavi, Abass; Høilund-Carlsen, Poul Flemming; Godballe, Christian

2017-12-01

The purpose of this study was to determine the detection rate of distant metastasis and synchronous cancer, comparing clinically used imaging strategies based on chest x-ray + head and neck MRI (CXR/MRI) and chest CT + head and neck MRI (CHCT/MRI) with 18 F-FDG PET/CT upfront in the diagnostic workup of patients with oral, pharyngeal, or laryngeal cancer. Methods: This was a prospective cohort study based on paired data. Consecutive patients with histologically verified primary head and squamous cell carcinoma at Odense University Hospital from September 2013 to March 2016 were considered for the study. Included patients underwent CXR/MRI and CHCT/MRI as well as PET/CT on the same day and before biopsy. Scans were read masked by separate teams of experienced nuclear physicians or radiologists. The true detection rate of distant metastasis and synchronous cancer was assessed for CXR/MRI, CHCT/MRI, and PET/CT. Results: A total of 307 patients were included. CXR/MRI correctly detected 3 (1%) patients with distant metastasis, CHCT/MRI detected 11 (4%) patients, and PET/CT detected 18 (6%) patients. The absolute differences of 5% and 2%, respectively, were statistically significant in favor of PET/CT. Also, PET/CT correctly detected 25 (8%) synchronous cancers, which was significantly more than CXR/MRI (3 patients, 1%) and CHCT/MRI (6 patients, 2%). The true detection rate of distant metastasis or synchronous cancer with PET/CT was 13% (40 patients), which was significantly higher than 2% (6 patients) for CXR/MRI and 6% (17 patients) for CHCT/MRI. Conclusion: A clinical imaging strategy based on PET/CT demonstrated a significantly higher detection rate of distant metastasis or synchronous cancer than strategies in current clinical imaging guidelines, of which European ones primarily recommend CXR/MRI, whereas U.S. guidelines preferably point to CHCT/MRI in patients with head and neck squamous cell carcinoma. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction.

PubMed

Morshed, R A; Gutova, M; Juliano, J; Barish, M E; Hawkins-Daarud, A; Oganesyan, D; Vazgen, K; Yang, T; Annala, A; Ahmed, A U; Aboody, K S; Swanson, K R; Moats, R A; Lesniak, M S

2015-01-01

In preclinical studies, neural stem cell (NSC)-based delivery of oncolytic virus has shown great promise in the treatment of malignant glioma. Ensuring the success of this therapy will require critical evaluation of the spatial distribution of virus after NSC transplantation. In this study, the patient-derived GBM43 human glioma line was established in the brain of athymic nude mice, followed by the administration of NSCs loaded with conditionally replicating oncolytic adenovirus (NSC-CRAd-S-pk7). We determined the tumor coverage potential of oncolytic adenovirus by examining NSC distribution using magnetic resonance (MR) imaging and by three-dimensional reconstruction from ex vivo tissue specimens. We demonstrate that unmodified NSCs and NSC-CRAd-S-pk7 exhibit a similar distribution pattern with most prominent localization occurring at the tumor margins. We were further able to visualize the accumulation of these cells at tumor sites via T2-weighted MR imaging as well as the spread of viral particles using immunofluorescence. Our analyses reveal that a single administration of oncolytic virus-loaded NSCs allows for up to 31% coverage of intracranial tumors. Such results provide valuable insights into the therapeutic potential of this novel viral delivery platform.

Quantitative characterization of the imaging limits of diffuse low-grade oligodendrogliomas.

PubMed

Gerin, Chloé; Pallud, Johan; Deroulers, Christophe; Varlet, Pascale; Oppenheim, Catherine; Roux, Francois-Xavier; Chrétien, Fabrice; Thomas, Stephen R; Grammaticos, Basile; Badoual, Mathilde

2013-10-01

Supratentorial diffuse low-grade gliomas in adults extend beyond maximal visible MRI-defined abnormalities, and a gap exists between the imaging signal changes and the actual tumor margins. Direct quantitative comparisons between imaging and histological analyses are lacking to date. However, they are of the utmost importance if one wishes to develop realistic models for diffuse glioma growth. In this study, we quantitatively compared the cell concentration and the edema fraction from human histological biopsy samples (BSs) performed inside and outside imaging abnormalities during serial imaging-based stereotactic biopsy of diffuse low-grade gliomas. The cell concentration was significantly higher in BSs located inside (1189 ± 378 cell/mm(2)) than outside (740 ± 124 cell/mm(2)) MRI-defined abnormalities (P = .0003). The edema fraction was significantly higher in BSs located inside (mean, 45% ± 23%) than outside (mean, 5 %± 9%) MRI-defined abnormalities (P < .0001). At borders of the MRI-defined abnormalities, 20% of the tissue surface area was occupied by edema and only 3% by tumor cells. The cycling cell concentration was significantly higher in BSs located inside (10 ± 12 cell/mm(2)), compared with outside (0.5 ± 0.9 cell/mm(2)), MRI-defined abnormalities (P = .0001). We showed that the margins of T2-weighted signal changes are mainly correlated with the edema fraction. In 62.5% of patients, the cycling tumor cell fraction (defined as the ratio of the cycling tumor cell concentration to the total number of tumor cells) was higher at the limits of the MRI-defined abnormalities than closer to the center of the tumor. In the remaining patients, the cycling tumor cell fraction increased towards the center of the tumor.

Using ferromagnetic nanoparticles with low Curie temperature for magnetic resonance imaging-guided thermoablation

PubMed Central

Herynek, Vít; Turnovcová, Karolína; Veverka, Pavel; Dědourková, Tereza; Žvátora, Pavel; Jendelová, Pavla; Gálisová, Andrea; Kosinová, Lucie; Jiráková, Klára; Syková, Eva

2016-01-01

Introduction Magnetic nanoparticles (NPs) represent a tool for use in magnetic resonance imaging (MRI)-guided thermoablation of tumors using an external high-frequency (HF) magnetic field. To avoid local overheating, perovskite NPs with a lower Curie temperature (Tc) were proposed for use in thermotherapy. However, deposited power decreases when approaching the Curie temperature and consequently may not be sufficient for effective ablation. The goal of the study was to test this hypothesis. Methods Perovskite NPs (Tc =66°C–74°C) were characterized and tested both in vitro and in vivo. In vitro, the cells suspended with NPs were exposed to a HF magnetic field together with control samples. In vivo, a NP suspension was injected into a induced tumor in rats. Distribution was checked by MRI and the rats were exposed to a HF field together with control animals. Apoptosis in the tissue was evaluated. Results and discussion In vitro, the high concentration of suspended NPs caused an increase of the temperature in the cell sample, leading to cell death. In vivo, MRI confirmed distribution of the NPs in the tumor. The temperature in the tumor with injected NPs did not increase substantially in comparison with animals without particles during HF exposure. We proved that the deposited power from the NPs is too small and that thermoregulation of the animal is sufficient to conduct the heat away. Histology did not detect substantially higher apoptosis in NP-treated animals after ablation. Conclusion Magnetic particles with low Tc can be tracked in vivo by MRI and heated by a HF field. The particles are capable of inducing cell apoptosis in suspensions in vitro at high concentrations only. However, their effect in the case of extracellular deposition in vivo is questionable due to low deposited power and active thermoregulation of the tissue. PMID:27540292

Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging

PubMed Central

2011-01-01

Background Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate in vivo. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs. Results Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated in vitro with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells. Conclusions The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use. PMID:21542946

Magnetic resonance imaging and X-ray microtomography studies of a gel-forming tablet formulation.

PubMed

Laity, P R; Mantle, M D; Gladden, L F; Cameron, R E

2010-01-01

The capabilities of two methods for investigating tablet swelling are investigated, based on a study of a model gel-forming system. Results from magnetic resonance imaging (MRI) were compared with results from a novel application of X-ray microtomography (XmicroT) to track the movements of embedded glass microsphere tracers as the model tablets swelled. MRI provided information concerning the movement of hydration fronts into the tablets and the composition of the swollen gel layer, which formed at the tablet surface and progressively thickened with time. Conversely, XmicroT revealed significant axial expansion within the tablet core, at short times and ahead of the hydration fronts, where there was insufficient water to be observed by MRI (estimated to be around 15% by weight for the system used here). Thus, MRI and XmicroT may be regarded as complementary methods for studying the hydration and swelling behaviour of tablets. Copyright 2009 Elsevier B.V. All rights reserved.

Sequence design and software environment for real-time navigation of a wireless ferromagnetic device using MRI system and single echo 3D tracking.

PubMed

Chanu, A; Aboussouan, E; Tamaz, S; Martel, S

2006-01-01

Software architecture for the navigation of a ferromagnetic untethered device in a 1D and 2D phantom environment is briefly described. Navigation is achieved using the real-time capabilities of a Siemens 1.5 T Avanto MRI system coupled with a dedicated software environment and a specially developed 3D tracking pulse sequence. Real-time control of the magnetic core is executed through the implementation of a simple PID controller. 1D and 2D experimental results are presented.

Retrospective respiratory self-gating and removal of bulk motion in pulmonary UTE MRI of neonates and adults

PubMed Central

Higano, NS; Hahn, AD; Tkach, JA; Cao, X; Walkup, LL; Thomen, RP; Merhar, SL; Kingma, PS; Fain, SB; Woods, JC

2016-01-01

PURPOSE To implement pulmonary 3D radial ultrashort echo-time (UTE) MRI in non-sedated, free-breathing neonates and adults with retrospective motion-tracking of respiratory and intermittent bulk motion, to obtain diagnostic-quality, respiratory-gated images. METHODS Pulmonary 3D radial UTE MRI was performed at 1.5T during free-breathing in neonates and adult volunteers for validation. Motion-tracking waveforms were obtained from the time-course of each free induction decay’s initial point (i.e. k-space center), allowing for respiratory-gated image reconstructions that excluded data acquired during bulk motion. Tidal volumes were calculated from end-expiration and end-inspiration images. Respiratory rates were calculated from the Fourier transform of the motion-tracking waveform during quiet-breathing, with comparison to physiologic prediction in neonates and validation with spirometry in adults. RESULTS High-quality respiratory-gated anatomic images were obtained at inspiration and expiration, with less respiratory blurring at the expense of signal-to-noise for narrower gating windows. Inspiration-expiration volume differences agreed with physiologic predictions (neonates; Bland-Altman bias = 6.2 mL) and spirometric values (adults; bias = 0.11 L). MRI-measured respiratory rates compared well with observed rates (biases = −0.5 and 0.2 breaths/min for neonates and adults, respectively). CONCLUSIONS 3D radial pulmonary UTE MRI allows for retrospective respiratory self-gating and removal of intermittent bulk motion in free-breathing, non-sedated neonates and adults. PMID:26972576

Tractography Verified by Intraoperative Magnetic Resonance Imaging and Subcortical Stimulation During Tumor Resection Near the Corticospinal Tract.

PubMed

Münnich, Timo; Klein, Jan; Hattingen, Elke; Noack, Anika; Herrmann, Eva; Seifert, Volker; Senft, Christian; Forster, Marie-Therese

2018-04-14

Tractography is a popular tool for visualizing the corticospinal tract (CST). However, results may be influenced by numerous variables, eg, the selection of seeding regions of interests (ROIs) or the chosen tracking algorithm. To compare different variable sets by correlating tractography results with intraoperative subcortical stimulation of the CST, correcting intraoperative brain shift by the use of intraoperative MRI. Seeding ROIs were created by means of motor cortex segmentation, functional MRI (fMRI), and navigated transcranial magnetic stimulation (nTMS). Based on these ROIs, tractography was run for each patient using a deterministic and a probabilistic algorithm. Tractographies were processed on pre- and postoperatively acquired data. Using a linear mixed effects statistical model, best correlation between subcortical stimulation intensity and the distance between tractography and stimulation sites was achieved by using the segmented motor cortex as seeding ROI and applying the probabilistic algorithm on preoperatively acquired imaging sequences. Tractographies based on fMRI or nTMS results differed very little, but with enlargement of positive nTMS sites the stimulation-distance correlation of nTMS-based tractography improved. Our results underline that the use of tractography demands for careful interpretation of its virtual results by considering all influencing variables.

Automatic Segmenting Structures in MRI's Based on Texture Analysis and Fuzzy Logic

NASA Astrophysics Data System (ADS)

Kaur, Mandeep; Rattan, Munish; Singh, Pushpinder

2017-12-01

The purpose of this paper is to present the variational method for geometric contours which helps the level set function remain close to the sign distance function, therefor it remove the need of expensive re-initialization procedure and thus, level set method is applied on magnetic resonance images (MRI) to track the irregularities in them as medical imaging plays a substantial part in the treatment, therapy and diagnosis of various organs, tumors and various abnormalities. It favors the patient with more speedy and decisive disease controlling with lesser side effects. The geometrical shape, the tumor's size and tissue's abnormal growth can be calculated by the segmentation of that particular image. It is still a great challenge for the researchers to tackle with an automatic segmentation in the medical imaging. Based on the texture analysis, different images are processed by optimization of level set segmentation. Traditionally, optimization was manual for every image where each parameter is selected one after another. By applying fuzzy logic, the segmentation of image is correlated based on texture features, to make it automatic and more effective. There is no initialization of parameters and it works like an intelligent system. It segments the different MRI images without tuning the level set parameters and give optimized results for all MRI's.

Hybrid MRI-Ultrasound acquisitions, and scannerless real-time imaging.

PubMed

Preiswerk, Frank; Toews, Matthew; Cheng, Cheng-Chieh; Chiou, Jr-Yuan George; Mei, Chang-Sheng; Schaefer, Lena F; Hoge, W Scott; Schwartz, Benjamin M; Panych, Lawrence P; Madore, Bruno

2017-09-01

To combine MRI, ultrasound, and computer science methodologies toward generating MRI contrast at the high frame rates of ultrasound, inside and even outside the MRI bore. A small transducer, held onto the abdomen with an adhesive bandage, collected ultrasound signals during MRI. Based on these ultrasound signals and their correlations with MRI, a machine-learning algorithm created synthetic MR images at frame rates up to 100 per second. In one particular implementation, volunteers were taken out of the MRI bore with the ultrasound sensor still in place, and MR images were generated on the basis of ultrasound signal and learned correlations alone in a "scannerless" manner. Hybrid ultrasound-MRI data were acquired in eight separate imaging sessions. Locations of liver features, in synthetic images, were compared with those from acquired images: The mean error was 1.0 pixel (2.1 mm), with best case 0.4 and worst case 4.1 pixels (in the presence of heavy coughing). For results from outside the bore, qualitative validation involved optically tracked ultrasound imaging with/without coughing. The proposed setup can generate an accurate stream of high-speed MR images, up to 100 frames per second, inside or even outside the MR bore. Magn Reson Med 78:897-908, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Intra-coil interactions in split gradient coils in a hybrid MRI-LINAC system.

PubMed

Tang, Fangfang; Freschi, Fabio; Sanchez Lopez, Hector; Repetto, Maurizio; Liu, Feng; Crozier, Stuart

2016-04-01

An MRI-LINAC system combines a magnetic resonance imaging (MRI) system with a medical linear accelerator (LINAC) to provide image-guided radiotherapy for targeting tumors in real-time. In an MRI-LINAC system, a set of split gradient coils is employed to produce orthogonal gradient fields for spatial signal encoding. Owing to this unconventional gradient configuration, eddy currents induced by switching gradient coils on and off may be of particular concern. It is expected that strong intra-coil interactions in the set will be present due to the constrained return paths, leading to potential degradation of the gradient field linearity and image distortion. In this study, a series of gradient coils with different track widths have been designed and analyzed to investigate the electromagnetic interactions between coils in a split gradient set. A driving current, with frequencies from 100 Hz to 10 kHz, was applied to study the inductive coupling effects with respect to conductor geometry and operating frequency. It was found that the eddy currents induced in the un-energized coils (hereby-referred to as passive coils) positively correlated with track width and frequency. The magnetic field induced by the eddy currents in the passive coils with wide tracks was several times larger than that induced by eddy currents in the cold shield of cryostat. The power loss in the passive coils increased with the track width. Therefore, intra-coil interactions should be included in the coil design and analysis process. Copyright © 2016 Elsevier Inc. All rights reserved.

Carbon-Based Nanostructures as Advanced Contrast Agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Ananta Narayanan, Jeyarama S.

2011-12-01

Superparamagnetic carbon-based nanostructures are presented as contrast agents (CAs) for advanced imaging applications such as cellular and molecular imaging using magnetic resonance imaging (MRI). Gadolinium-loaded, ultra-short single-walled carbon nanotubes (gadonanotubes; GNTs) are shown to have extremely high r1 relaxivities (contrast enhancement efficacy), especially at low-magnetic field strengths. The inherent lipophilicity of GNTs provides them the ability to image cells at low magnetic field strength. A carboxylated dextran-coated GNT (GadoDex) has been synthesized and proposed as a new biocompatible high-performance MRI CA. The r1 relaxivity is ca. 20 times greater than for other paramagnetic Gd-based CAs. This enhanced relaxivity for GadoDex is due to the synergistic effects of an increased molecular tumbling time (tauR) and a faster proton exchange rate (taum). GNTs also exhibit very large transverse relaxivities (r2) at high magnetic fields (≥ 3 T). The dependence of the transverse relaxation rates (especially R2*) of labeled cells on GNT concentration offers the possibility to quantify cell population in vivo using R2* mapping. The cell-labeling efficiency and high transverse relaxivities of GNTs has enabled the first non-iron oxide-based single-cell imaging using MRI. The residual metal catalyst particles of SWNT materials also have transverse relaxation properties. All of the SWNT materials exhibit superior transverse relaxation properties. However, purified SWNTs and US-tubes with less residual metal content exhibit better transverse relaxivities (r2), demonstrating the importance of the SWNT structure for enhanced MRI CA performance. A strategy to improve the r1 relaxivity of Gd-CAs by geometrically confining them within porous silicon particles (SiMPs) has been investigated. The enhancement in relaxivity is attributed to the slow diffusion of water molecules through the pores and the increase in the molecular tumbling time of the nanoconstruct. The universality of the strategy has been demonstrated for GNTs, gadofullerols and clinically-used MagnevistRTM. In summary, primary nanoscale confinement of Gd3+ ions in US-tubes has resulted in a new class of CAs which could revitalize low-field contrast-enhanced MRI, while extending and complementing current high-field MRI technology, as well. The observed boost in relaxivity upon a secondary nanoscale confinement of Gd-CAs within SiMPs suggests that additional unforeseen nanoscale effects may have the potential to further boost performance of MRI CAs.

Reward magnitude tracking by neural populations in ventral striatum

PubMed Central

Fiallos, Ana M.; Bricault, Sarah J.; Cai, Lili X.; Worku, Hermoon A.; Colonnese, Matthew T.; Westmeyer, Gil; Jasanoff, Alan

2017-01-01

Evaluation of the magnitudes of intrinsically rewarding stimuli is essential for assigning value and guiding behavior. By combining parametric manipulation of a primary reward, medial forebrain bundle (MFB) microstimulation, with functional magnetic imaging (fMRI) in rodents, we delineated a broad network of structures activated by behaviorally characterized levels of rewarding stimulation. Correlation of psychometric behavioral measurements with fMRI response magnitudes revealed regions whose activity corresponded closely to the subjective magnitude of rewards. The largest and most reliable focus of reward magnitude tracking was observed in the shell region of the nucleus accumbens (NAc). Although the nonlinear nature of neurovascular coupling complicates interpretation of fMRI findings in precise neurophysiological terms, reward magnitude tracking was not observed in vascular compartments and could not be explained by saturation of region-specific hemodynamic responses. In addition, local pharmacological inactivation of NAc changed the profile of animals’ responses to rewards of different magnitudes without altering mean reward response rates, further supporting a hypothesis that neural population activity in this region contributes to assessment of reward magnitudes. PMID:27789262

Optofluidic solar concentrators using electrowetting tracking: Concept, design, and characterization

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

Cheng, JT; Park, S; Chen, CL

2013-03-01

We introduce a novel optofluidic solar concentration system based on electrowetting tracking. With two immiscible fluids in a transparent cell, we can actively control the orientation of fluid fluid interface via electrowetting. The naturally-formed meniscus between the two liquids can function as a dynamic optical prism for solar tracking and sunlight steering. An integrated optofluidic solar concentrator can be constructed from the liquid prism tracker in combination with a fixed and static optical condenser (Fresnel lens). Therefore, the liquid prisms can adaptively focus sunlight on a concentrating photovoltaic (CPV) cell sitting on the focus of the Fresnel lens as themore » sun moves. Because of the unique design, electrowetting tracking allows the concentrator to adaptively track both the daily and seasonal changes of the sun's orbit (dual-axis tracking) without bulky, expensive and inefficient mechanical moving parts. This approach can potentially reduce capital costs for CPV and increases operational efficiency by eliminating the power consumption of mechanical tracking. Importantly, the elimination of bulky tracking hardware and quiet operation will allow extensive residential deployment of concentrated solar power. In comparison with traditional silicon-based photovoltaic (PV) solar cells, the electrowetting-based self-tracking technology will generate,similar to 70% more green energy with a 50% cost reduction. (C) 2013 Elsevier Ltd. All rights reserved.« less

Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo.

PubMed

Bardhan, Rizia; Chen, Wenxue; Bartels, Marc; Perez-Torres, Carlos; Botero, Maria F; McAninch, Robin Ward; Contreras, Alejandro; Schiff, Rachel; Pautler, Robia G; Halas, Naomi J; Joshi, Amit

2010-12-08

Nanoparticle-based therapeutics with local delivery and external electromagnetic field modulation holds extraordinary promise for soft-tissue cancers such as breast cancer; however, knowledge of the distribution and fate of nanoparticles in vivo is crucial for clinical translation. Here we demonstrate that multiple diagnostic capabilities can be introduced in photothermal therapeutic nanocomplexes by simultaneously enhancing both near-infrared fluorescence and magnetic resonance imaging (MRI). We track nanocomplexes in vivo, examining the influence of HER2 antibody targeting on nanocomplex distribution over 72 h. This approach provides valuable, detailed information regarding the distribution and fate of complex nanoparticles designed for specific diagnostic and therapeutic functions.

Tracking of Multimodal Therapeutic Nanocomplexes Targeting Breast Cancer in Vivo

PubMed Central

Bardhan, Rizia; Chen, Wenxue; Bartels, Marc; Perez-Torres, Carlos; Botero, Maria F.; McAninch, Robin Ward; Contreras, Alejandro; Schiff, Rachel; Pautler, Robia G.; Halas, Naomi J.; Joshi, Amit

2014-01-01

Nanoparticle-based therapeutics with local delivery and external electromagnetic field modulation holds extraordinary promise for soft-tissue cancers such as breast cancer; however, knowledge of the distribution and fate of nanoparticles in vivo is crucial for clinical translation. Here we demonstrate that multiple diagnostic capabilities can be introduced in photothermal therapeutic nanocomplexes by simultaneously enhancing both near-infrared fluorescence and magnetic resonance imaging (MRI). We track nanocomplexes in vivo, examining the influence of HER2 antibody targeting on nanocomplex distribution over 72 h. This approach provides valuable, detailed information regarding the distribution and fate of complex nanoparticles designed for specific diagnostic and therapeutic functions. PMID:21090693

Efficient MRI labeling of endothelial progenitor cells: design of thiolated surface stabilized superparamagnetic iron oxide nanoparticles.

PubMed

Shahnaz, Gul; Kremser, Christian; Reinisch, Andreas; Vetter, Anja; Laffleur, Flavia; Rahmat, Deni; Iqbal, Javed; Dünnhaupt, Sarah; Salvenmoser, Willi; Tessadri, Richard; Griesser, Ulrich; Bernkop-Schnürch, Andreas

2013-11-01

The aim of this study was to design thiolated surface stabilized superparamagnetic iron oxide nanoparticles (TSS-SPIONs) for efficient internalization with high MRI sensitivity. TSS-SPIONs were developed by chelation between thiolated chitosan-thioglycolic acid (chitosan-TGA) hydrogel and iron ions (Fe(2+)/Fe(3+)). Likely, unmodified chitosan hydrogel SPIONs (UC-SPIONs) and uncoated SPIONs were used as control. Moreover, TSS-SPIONs were investigated regarding to their iron core size, hydrodynamic diameter, zeta potential, iron contents, molar relaxivities (r1 and r2), and cellular internalization. TSS-SPIONs demonstrated an iron oxide core diameter (crystallite size by XRD) of 3.1 ± 0.02 nm, a hydrodynamic diameter of 94 ± 20 nm, a zeta potential of +21 ± 5 mV, and an iron content of 3.6 ± 0.9 mg/mL. In addition, internalization of TSS-SPIONs into human endothelial progenitor cells (EPC) from umbilical cord blood was more than threefold and 17-fold higher in contrast to UC-SPIONs and SPIONs, respectively. With twofold lower incubation iron concentration of TSS-SPIONs, more than threefold higher internalization was achieved as compared to Resovist®. Also, cell viability of more than 90% was observed in the presence of TSS-SPIONs after 24h. The molar MR relaxivities (r2) value at 1.5 T was threefold higher than that of Resovist® and demonstrated that TSS-SPIONs have the potential as very effective T2 contrast-enhancement agent. According to these findings, TSS-SPIONs with efficient internalization, lower cytotoxicity, and high MRI sensitivity seem to be promising for cell tracking. Copyright © 2013 Elsevier B.V. All rights reserved.

Tumor Lysing Genetically Engineered T Cells Loaded with Multi-Modal Imaging Agents

NASA Astrophysics Data System (ADS)

Bhatnagar, Parijat; Alauddin, Mian; Bankson, James A.; Kirui, Dickson; Seifi, Payam; Huls, Helen; Lee, Dean A.; Babakhani, Aydin; Ferrari, Mauro; Li, King C.; Cooper, Laurence J. N.

2014-03-01

Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert anti-tumor effect by identifying tumor-associated antigen (TAA), independent of major histocompatibility complex. For maximal efficacy and safety of adoptively transferred cells, imaging their biodistribution is critical. This will determine if cells home to the tumor and assist in moderating cell dose. Here, T cells are modified to express CAR. An efficient, non-toxic process with potential for cGMP compliance is developed for loading high cell number with multi-modal (PET-MRI) contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION-64Cu). This can now be potentially used for 64Cu-based whole-body PET to detect T cell accumulation region with high-sensitivity, followed by SPION-based MRI of these regions for high-resolution anatomically correlated images of T cells. CD19-specific-CAR+SPIONpos T cells effectively target in vitro CD19+ lymphoma.

Combined diffusion-weighted and functional magnetic resonance imaging reveals a temporal-occipital network involved in auditory-visual object processing

PubMed Central

Beer, Anton L.; Plank, Tina; Meyer, Georg; Greenlee, Mark W.

2013-01-01

Functional magnetic resonance imaging (MRI) showed that the superior temporal and occipital cortex are involved in multisensory integration. Probabilistic fiber tracking based on diffusion-weighted MRI suggests that multisensory processing is supported by white matter connections between auditory cortex and the temporal and occipital lobe. Here, we present a combined functional MRI and probabilistic fiber tracking study that reveals multisensory processing mechanisms that remained undetected by either technique alone. Ten healthy participants passively observed visually presented lip or body movements, heard speech or body action sounds, or were exposed to a combination of both. Bimodal stimulation engaged a temporal-occipital brain network including the multisensory superior temporal sulcus (msSTS), the lateral superior temporal gyrus (lSTG), and the extrastriate body area (EBA). A region-of-interest (ROI) analysis showed multisensory interactions (e.g., subadditive responses to bimodal compared to unimodal stimuli) in the msSTS, the lSTG, and the EBA region. Moreover, sounds elicited responses in the medial occipital cortex. Probabilistic tracking revealed white matter tracts between the auditory cortex and the medial occipital cortex, the inferior occipital cortex (IOC), and the superior temporal sulcus (STS). However, STS terminations of auditory cortex tracts showed limited overlap with the msSTS region. Instead, msSTS was connected to primary sensory regions via intermediate nodes in the temporal and occipital cortex. Similarly, the lSTG and EBA regions showed limited direct white matter connections but instead were connected via intermediate nodes. Our results suggest that multisensory processing in the STS is mediated by separate brain areas that form a distinct network in the lateral temporal and inferior occipital cortex. PMID:23407860

CellProfiler Tracer: exploring and validating high-throughput, time-lapse microscopy image data.

PubMed

Bray, Mark-Anthony; Carpenter, Anne E

2015-11-04

Time-lapse analysis of cellular images is an important and growing need in biology. Algorithms for cell tracking are widely available; what researchers have been missing is a single open-source software package to visualize standard tracking output (from software like CellProfiler) in a way that allows convenient assessment of track quality, especially for researchers tuning tracking parameters for high-content time-lapse experiments. This makes quality assessment and algorithm adjustment a substantial challenge, particularly when dealing with hundreds of time-lapse movies collected in a high-throughput manner. We present CellProfiler Tracer, a free and open-source tool that complements the object tracking functionality of the CellProfiler biological image analysis package. Tracer allows multi-parametric morphological data to be visualized on object tracks, providing visualizations that have already been validated within the scientific community for time-lapse experiments, and combining them with simple graph-based measures for highlighting possible tracking artifacts. CellProfiler Tracer is a useful, free tool for inspection and quality control of object tracking data, available from http://www.cellprofiler.org/tracer/.

Tracking of cell nuclei for assessment of in vitro uptake kinetics in ultrasound-mediated drug delivery using fibered confocal fluorescence microscopy.

PubMed

Derieppe, Marc; de Senneville, Baudouin Denis; Kuijf, Hugo; Moonen, Chrit; Bos, Clemens

2014-10-01

Previously, we demonstrated the feasibility to monitor ultrasound-mediated uptake of a cell-impermeable model drug in real time with fibered confocal fluorescence microscopy. Here, we present a complete post-processing methodology, which corrects for cell displacements, to improve the accuracy of pharmacokinetic parameter estimation. Nucleus detection was performed based on the radial symmetry transform algorithm. Cell tracking used an iterative closest point approach. Pharmacokinetic parameters were calculated by fitting a two-compartment model to the time-intensity curves of individual cells. Cells were tracked successfully, improving time-intensity curve accuracy and pharmacokinetic parameter estimation. With tracking, 93 % of the 370 nuclei showed a fluorescence signal variation that was well-described by a two-compartment model. In addition, parameter distributions were narrower, thus increasing precision. Dedicated image analysis was implemented and enabled studying ultrasound-mediated model drug uptake kinetics in hundreds of cells per experiment, using fiber-based confocal fluorescence microscopy.

WE-H-BRA-08: A Monte Carlo Cell Nucleus Model for Assessing Cell Survival Probability Based On Particle Track Structure Analysis

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

Lee, B; Georgia Institute of Technology, Atlanta, GA; Wang, C

Purpose: To correlate the damage produced by particles of different types and qualities to cell survival on the basis of nanodosimetric analysis and advanced DNA structures in the cell nucleus. Methods: A Monte Carlo code was developed to simulate subnuclear DNA chromatin fibers (CFs) of 30nm utilizing a mean-free-path approach common to radiation transport. The cell nucleus was modeled as a spherical region containing 6000 chromatin-dense domains (CDs) of 400nm diameter, with additional CFs modeled in a sparser interchromatin region. The Geant4-DNA code was utilized to produce a particle track database representing various particles at different energies and dose quantities.more » These tracks were used to stochastically position the DNA structures based on their mean free path to interaction with CFs. Excitation and ionization events intersecting CFs were analyzed using the DBSCAN clustering algorithm for assessment of the likelihood of producing DSBs. Simulated DSBs were then assessed based on their proximity to one another for a probability of inducing cell death. Results: Variations in energy deposition to chromatin fibers match expectations based on differences in particle track structure. The quality of damage to CFs based on different particle types indicate more severe damage by high-LET radiation than low-LET radiation of identical particles. In addition, the model indicates more severe damage by protons than of alpha particles of same LET, which is consistent with differences in their track structure. Cell survival curves have been produced showing the L-Q behavior of sparsely ionizing radiation. Conclusion: Initial results indicate the feasibility of producing cell survival curves based on the Monte Carlo cell nucleus method. Accurate correlation between simulated DNA damage to cell survival on the basis of nanodosimetric analysis can provide insight into the biological responses to various radiation types. Current efforts are directed at producing cell survival curves for high-LET radiation.« less

A low cost fMRI-compatible tracking system using the Nintendo Wii remote.

PubMed

Modroño, Cristián; Rodríguez-Hernández, Antonio F; Marcano, Francisco; Navarrete, Gorka; Burunat, Enrique; Ferrer, Marta; Monserrat, Raquel; González-Mora, José L

2011-11-15

It is sometimes necessary during functional magnetic resonance imaging (fMRI) experiments to capture different movements made by the subjects, e.g. to enable them to control an item or to analyze its kinematics. The aim of this work is to present an inexpensive hand tracking system suitable for use in a high field MRI environment. It works by introducing only one light-emitting diode (LED) in the magnet room, and by receiving its signal with a Nintendo Wii remote (the primary controller for the Nintendo Wii console) placed outside in the control room. Thus, it is possible to take high spatial and temporal resolution registers of a moving point that, in this case, is held by the hand. We tested it using a ball and racket virtual game inside a 3 Tesla MRI scanner to demonstrate the usefulness of the system. The results show the involvement of a number of areas (mainly occipital and frontal, but also parietal and temporal) when subjects are trying to stop an object that is approaching from a first person perspective, matching previous studies performed with related visuomotor tasks. The system presented here is easy to implement, easy to operate and does not produce important head movements or artifacts in the acquired images. Given its low cost and ready availability, the method described here is ideal for use in basic and clinical fMRI research to track one or more moving points that can correspond to limbs, fingers or any other object whose position needs to be known. Copyright © 2011 Elsevier B.V. All rights reserved.

Method for enhancing cell penetration of Gd3+-based MRI contrast agents by conjugation with hydrophobic fluorescent dyes.

PubMed

Yamane, Takehiro; Hanaoka, Kenjiro; Muramatsu, Yasuaki; Tamura, Keita; Adachi, Yusuke; Miyashita, Yasushi; Hirata, Yasunobu; Nagano, Tetsuo

2011-11-16

Gadolinium ion (Gd(3+)) complexes are commonly used as magnetic resonance imaging (MRI) contrast agents to enhance signals in T(1)-weighted MR images. Recently, several methods to achieve cell-permeation of Gd(3+) complexes have been reported, but more general and efficient methodology is needed. In this report, we describe a novel method to achieve cell permeation of Gd(3+) complexes by using hydrophobic fluorescent dyes as a cell-permeability-enhancing unit. We synthesized Gd(3+) complexes conjugated with boron dipyrromethene (BDP-Gd) and Cy7 dye (Cy7-Gd), and showed that these conjugates can be introduced efficiently into cells. To examine the relationship between cell permeability and dye structure, we further synthesized a series of Cy7-Gd derivatives. On the basis of MR imaging, flow cytometry, and ICP-MS analysis of cells loaded with Cy7-Gd derivatives, highly hydrophobic and nonanionic dyes were effective for enhancing cell permeation of Gd(3+) complexes. Furthermore, the behavior of these Cy7-Gd derivatives was examined in mice. Thus, conjugation of hydrophobic fluorescent dyes appears to be an effective approach to improve the cell permeability of Gd(3+) complexes, and should be applicable for further development of Gd(3+)-based MRI contrast agents.

Automated cell tracking and analysis in phase-contrast videos (iTrack4U): development of Java software based on combined mean-shift processes.

PubMed

Cordelières, Fabrice P; Petit, Valérie; Kumasaka, Mayuko; Debeir, Olivier; Letort, Véronique; Gallagher, Stuart J; Larue, Lionel

2013-01-01

Cell migration is a key biological process with a role in both physiological and pathological conditions. Locomotion of cells during embryonic development is essential for their correct positioning in the organism; immune cells have to migrate and circulate in response to injury. Failure of cells to migrate or an inappropriate acquisition of migratory capacities can result in severe defects such as altered pigmentation, skull and limb abnormalities during development, and defective wound repair, immunosuppression or tumor dissemination. The ability to accurately analyze and quantify cell migration is important for our understanding of development, homeostasis and disease. In vitro cell tracking experiments, using primary or established cell cultures, are often used to study migration as cells can quickly and easily be genetically or chemically manipulated. Images of the cells are acquired at regular time intervals over several hours using microscopes equipped with CCD camera. The locations (x,y,t) of each cell on the recorded sequence of frames then need to be tracked. Manual computer-assisted tracking is the traditional method for analyzing the migratory behavior of cells. However, this processing is extremely tedious and time-consuming. Most existing tracking algorithms require experience in programming languages that are unfamiliar to most biologists. We therefore developed an automated cell tracking program, written in Java, which uses a mean-shift algorithm and ImageJ as a library. iTrack4U is a user-friendly software. Compared to manual tracking, it saves considerable amount of time to generate and analyze the variables characterizing cell migration, since they are automatically computed with iTrack4U. Another major interest of iTrack4U is the standardization and the lack of inter-experimenter differences. Finally, iTrack4U is adapted for phase contrast and fluorescent cells.

The development of a 4D treatment planning methodology to simulate the tracking of central lung tumors in an MRI-linac.

PubMed

Al-Ward, Shahad M; Kim, Anthony; McCann, Claire; Ruschin, Mark; Cheung, Patrick; Sahgal, Arjun; Keller, Brian M

2018-01-01

Targeting and tracking of central lung tumors may be feasible on the Elekta MRI-linac (MRL) due to the soft-tissue visualization capabilities of MRI. The purpose of this work is to develop a novel treatment planning methodology to simulate tracking of central lung tumors with the MRL and to quantify the benefits in OAR sparing compared with the ITV approach. Full 4D-CT datasets for five central lung cancer patients were selected to simulate the condition of having 4D-pseudo-CTs derived from 4D-MRI data available on the MRL with real-time tracking capabilities. We used the MRL treatment planning system to generate two plans: (a) with a set of MLC-defined apertures around the target at each phase of the breathing ("4D-MRL" method); (b) with a fixed set of fields encompassing the maximum inhale and exhale of the breathing cycle ("ITV" method). For both plans, dose accumulation was performed onto a reference phase. To further study the potential benefits of a 4D-MRL method, the results were stratified by tumor motion amplitude, OAR-to-tumor proximity, and the relative OAR motion (ROM). With the 4D-MRL method, the reduction in mean doses was up to 3.0 Gy and 1.9 Gy for the heart and the lung. Moreover, the lung's V12.5 Gy was spared by a maximum of 300 cc. Maximum doses to serial organs were reduced by up to 6.1 Gy, 1.5 Gy, and 9.0 Gy for the esophagus, spinal cord, and the trachea, respectively. OAR dose reduction with our method depended on the tumor motion amplitude and the ROM. Some OARs with large ROMs and in close proximity to the tumor benefited from tracking despite small tumor amplitudes. We developed a novel 4D tracking methodology for the MRL for central lung tumors and quantified the potential dosimetric benefits compared with our current ITV approach. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Modular Carbon and Gold Nanoparticles for High Field MR Imaging and Theranostics

NASA Astrophysics Data System (ADS)

Rammohan, Nikhil

The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth and metastatic potential within the intact organism. Magnetic Resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies. Accordingly, we have developed carbon- and gold-nanoparticles coupled to gadolinium(III) [Gd(III)] chelates for T1-weighted MR imaging that demonstrated remarkable properties for cell tracking in vitro and in vivo.. We created nanodiamond-Gd(III) aggregates (NDG) by peptide coupling Gd(III) chelates to aminated nanodiamonds. NDG had high relaxivity independent of field strength (unprecedented for Gd(III)-nanoparticle conjugates), and demonstrated a 300-fold increase in cellular delivery of Gd(III) compared to clinical Gd(III) chelates. Further, we were able to monitor the tumor growth of NDG-labeled flank tumors by T1-weighted MRI for 26 days in vivo, longer than reported for other MR CAs or nuclear agents. Further, theranostic nanodiamond-gadolinium(III)-doxorubicin (ND-Gd-Dox) aggregates were generated by conjugating doxorubicin (ND-Gd-Dox), which enabled efficient cancer chemotherapy in breast cancer cells. Further, we synthesized Gd(III)-gold nanoconjugates (Gd AuNPs) with varied chelate structure and nanoparticle-chelate linker length. Significantly enhanced cell labeling was demonstrated compared to previous gadolinium-gold-DNA nanoconstructs. Differences in Gd(III) loading, surface packing and cell uptake were observed between four different Gd AuNP formulations suggesting that linker length and surface charge play an important role in cell labeling. The best performing Gd AuNPs afforded 23.6 +/- 3.6 fmol of Gd(III) per cell at an incubation concentration of 27.5 microM. This efficiency of Gd(III) payload delivery (Gd(III)/cell normalized to dose) exceeds that of previously Gd(III)-Au conjugates and most other Gd(III)-nanoparticle formulations. Finally, Gd AuNPs were the first MR CAs of any type to effectively image the pancreas in vivo. . In summary, both Gd AuNPs and NDG support future MR-mediated cell tracking and theranostic applications in whole-animal models.

Dose Dependent Side Effect of Superparamagnetic Iron Oxide Nanoparticle Labeling on Cell Motility in Two Fetal Stem Cell Populations

PubMed Central

Diana, Valentina; Bossolasco, Patrizia; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

2013-01-01

Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies. PMID:24244310

Breast cancer early detection via tracking of skin back-scattered secondary speckle patterns

NASA Astrophysics Data System (ADS)

Bennett, Aviya; Sirkis, Talia; Beiderman, Yevgeny; Agdarov, Sergey; Beiderman, Yafim; Zalevsky, Zeev

2018-02-01

Breast cancer has become a major cause of death among women. The lifetime risk of a woman developing this disease has been established as one in eight. The most useful way to reduce breast cancer death is to treat the disease as early as possible. The existing methods of early diagnostics of breast cancer are mainly based on screening mammography or Magnetic Resonance Imaging (MRI) periodically conducted at medical facilities. In this paper the authors proposing a new approach for simple breast cancer detection. It is based on skin stimulation by sound waves, illuminating it by laser beam and tracking the reflected secondary speckle patterns. As first approach, plastic balls of different sizes were placed under the skin of chicken breast and detected by the proposed method.

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

Hu, L; Yin, F; Cai, J

Purpose: To develop a methodology of constructing physiological-based virtual thorax phantom based on hyperpolarized (HP) gas tagging MRI for evaluating deformable image registration (DIR). Methods: Three healthy subjects were imaged at both the end-of-inhalation (EOI) and the end-of-exhalation (EOE) phases using a high-resolution (2.5mm isovoxel) 3D proton MRI, as well as a hybrid MRI which combines HP gas tagging MRI and a low-resolution (4.5mm isovoxel) proton MRI. A sparse tagging displacement vector field (tDVF) was derived from the HP gas tagging MRI by tracking the displacement of tagging grids between EOI and EOE. Using the tDVF and the high-resolution MRmore » images, we determined the motion model of the entire thorax in the following two steps: 1) the DVF inside of lungs was estimated based on the sparse tDVF using a novel multi-step natural neighbor interpolation method; 2) the DVF outside of lungs was estimated from the DIR between the EOI and EOE images (Velocity AI). The derived motion model was then applied to the high-resolution EOI image to create a deformed EOE image, forming the virtual phantom where the motion model provides the ground truth of deformation. Five DIR methods were evaluated using the developed virtual phantom. Errors in DVF magnitude (Em) and angle (Ea) were determined and compared for each DIR method. Results: Among the five DIR methods, free form deformation produced DVF results that are most closely resembling the ground truth (Em=1.04mm, Ea=6.63°). The two DIR methods based on B-spline produced comparable results (Em=2.04mm, Ea=13.66°; and Em =2.62mm, Ea=17.67°), and the two optical-flow methods produced least accurate results (Em=7.8mm; Ea=53.04°; Em=4.45mm, Ea=31.02°). Conclusion: A methodology for constructing physiological-based virtual thorax phantom based on HP gas tagging MRI has been developed. Initial evaluation demonstrated its potential as an effective tool for robust evaluation of DIR in the lung.« less

An agent-based model identifies MRI regions of probable tumor invasion in a patient with glioblastoma

NASA Astrophysics Data System (ADS)

Chen, L. Leon; Ulmer, Stephan; Deisboeck, Thomas S.

2010-01-01

We present an application of a previously developed agent-based glioma model (Chen et al 2009 Biosystems 95 234-42) for predicting spatio-temporal tumor progression using a patient-specific MRI lattice derived from apparent diffusion coefficient (ADC) data. Agents representing collections of migrating glioma cells are initialized based upon voxels at the outer border of the tumor identified on T1-weighted (Gd+) MRI at an initial time point. These simulated migratory cells exhibit a specific biologically inspired spatial search paradigm, representing a weighting of the differential contribution from haptotactic permission and biomechanical resistance on the migration decision process. ADC data from 9 months after the initial tumor resection were used to select the best search paradigm for the simulation, which was initiated using data from 6 months after the initial operation. Using this search paradigm, 100 simulations were performed to derive a probabilistic map of tumor invasion locations. The simulation was able to successfully predict a recurrence in the dorsal/posterior aspect long before it was depicted on T1-weighted MRI, 18 months after the initial operation.

An agent-based model identifies MRI regions of probable tumor invasion in a patient with glioblastoma.

PubMed

Chen, L Leon; Ulmer, Stephan; Deisboeck, Thomas S

2010-01-21

We present an application of a previously developed agent-based glioma model (Chen et al 2009 Biosystems 95 234-42) for predicting spatio-temporal tumor progression using a patient-specific MRI lattice derived from apparent diffusion coefficient (ADC) data. Agents representing collections of migrating glioma cells are initialized based upon voxels at the outer border of the tumor identified on T1-weighted (Gd+) MRI at an initial time point. These simulated migratory cells exhibit a specific biologically inspired spatial search paradigm, representing a weighting of the differential contribution from haptotactic permission and biomechanical resistance on the migration decision process. ADC data from 9 months after the initial tumor resection were used to select the best search paradigm for the simulation, which was initiated using data from 6 months after the initial operation. Using this search paradigm, 100 simulations were performed to derive a probabilistic map of tumor invasion locations. The simulation was able to successfully predict a recurrence in the dorsal/posterior aspect long before it was depicted on T1-weighted MRI, 18 months after the initial operation.

Tracking the mammary architectural features and detecting breast cancer with magnetic resonance diffusion tensor imaging.

PubMed

Nissan, Noam; Furman-Haran, Edna; Feinberg-Shapiro, Myra; Grobgeld, Dov; Eyal, Erez; Zehavi, Tania; Degani, Hadassa

2014-12-15

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

The development of an MRI lesion quantifying system for multiple sclerosis patients undergoing treatment

NASA Astrophysics Data System (ADS)

Moin, Paymann; Ma, Kevin; Amezcua, Lilyana; Gertych, Arkadiusz; Liu, Brent

2009-02-01

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that affects approximately 2.5 million people worldwide. Magnetic resonance imaging (MRI) is an established tool for the assessment of disease activity, progression and response to treatment. The progression of the disease is variable and requires routine follow-up imaging studies. Currently, MRI quantification of multiple sclerosis requires a manual approach to lesion measurement and yields an estimate of lesion volume and interval change. In the setting of several prior studies and a long treatment history, trends related to treatment change quickly become difficult to extrapolate. Our efforts seek to develop an imaging informatics based MS lesion computer aided detection (CAD) package to quantify and track MS lesions including lesion load, volume, and location. Together, with select clinical parameters, this data will be incorporated into an MS specific e- Folder to provide decision support to evaluate and assess treatment options for MS in a manner tailored specifically to an individual based on trends in MS presentation and progression.

Accurately tracking single-cell movement trajectories in microfluidic cell sorting devices.

PubMed

Jeong, Jenny; Frohberg, Nicholas J; Zhou, Enlu; Sulchek, Todd; Qiu, Peng

2018-01-01

Microfluidics are routinely used to study cellular properties, including the efficient quantification of single-cell biomechanics and label-free cell sorting based on the biomechanical properties, such as elasticity, viscosity, stiffness, and adhesion. Both quantification and sorting applications require optimal design of the microfluidic devices and mathematical modeling of the interactions between cells, fluid, and the channel of the device. As a first step toward building such a mathematical model, we collected video recordings of cells moving through a ridged microfluidic channel designed to compress and redirect cells according to cell biomechanics. We developed an efficient algorithm that automatically and accurately tracked the cell trajectories in the recordings. We tested the algorithm on recordings of cells with different stiffness, and showed the correlation between cell stiffness and the tracked trajectories. Moreover, the tracking algorithm successfully picked up subtle differences of cell motion when passing through consecutive ridges. The algorithm for accurately tracking cell trajectories paves the way for future efforts of modeling the flow, forces, and dynamics of cell properties in microfluidics applications.

A magnetic resonance imaging study on the articulatory and acoustic speech parameters of Malay vowels

PubMed Central

2014-01-01

The phonetic properties of six Malay vowels are investigated using magnetic resonance imaging (MRI) to visualize the vocal tract in order to obtain dynamic articulatory parameters during speech production. To resolve image blurring due to the tongue movement during the scanning process, a method based on active contour extraction is used to track tongue contours. The proposed method efficiently tracks tongue contours despite the partial blurring of MRI images. Consequently, the articulatory parameters that are effectively measured as tongue movement is observed, and the specific shape of the tongue and its position for all six uttered Malay vowels are determined. Speech rehabilitation procedure demands some kind of visual perceivable prototype of speech articulation. To investigate the validity of the measured articulatory parameters based on acoustic theory of speech production, an acoustic analysis based on the uttered vowels by subjects has been performed. As the acoustic speech and articulatory parameters of uttered speech were examined, a correlation between formant frequencies and articulatory parameters was observed. The experiments reported a positive correlation between the constriction location of the tongue body and the first formant frequency, as well as a negative correlation between the constriction location of the tongue tip and the second formant frequency. The results demonstrate that the proposed method is an effective tool for the dynamic study of speech production. PMID:25060583

A magnetic resonance imaging study on the articulatory and acoustic speech parameters of Malay vowels.

PubMed

Zourmand, Alireza; Mirhassani, Seyed Mostafa; Ting, Hua-Nong; Bux, Shaik Ismail; Ng, Kwan Hoong; Bilgen, Mehmet; Jalaludin, Mohd Amin

2014-07-25

The phonetic properties of six Malay vowels are investigated using magnetic resonance imaging (MRI) to visualize the vocal tract in order to obtain dynamic articulatory parameters during speech production. To resolve image blurring due to the tongue movement during the scanning process, a method based on active contour extraction is used to track tongue contours. The proposed method efficiently tracks tongue contours despite the partial blurring of MRI images. Consequently, the articulatory parameters that are effectively measured as tongue movement is observed, and the specific shape of the tongue and its position for all six uttered Malay vowels are determined.Speech rehabilitation procedure demands some kind of visual perceivable prototype of speech articulation. To investigate the validity of the measured articulatory parameters based on acoustic theory of speech production, an acoustic analysis based on the uttered vowels by subjects has been performed. As the acoustic speech and articulatory parameters of uttered speech were examined, a correlation between formant frequencies and articulatory parameters was observed. The experiments reported a positive correlation between the constriction location of the tongue body and the first formant frequency, as well as a negative correlation between the constriction location of the tongue tip and the second formant frequency. The results demonstrate that the proposed method is an effective tool for the dynamic study of speech production.

Assessment of Automated Analyses of Cell Migration on Flat and Nanostructured Surfaces

PubMed Central

Grădinaru, Cristian; Łopacińska, Joanna M.; Huth, Johannes; Kestler, Hans A.; Flyvbjerg, Henrik; Mølhave, Kristian

2012-01-01

Motility studies of cells often rely on computer software that analyzes time-lapse recorded movies and establishes cell trajectories fully automatically. This raises the question of reproducibility of results, since different programs could yield significantly different results of such automated analysis. The fact that the segmentation routines of such programs are often challenged by nanostructured surfaces makes the question more pertinent. Here we illustrate how it is possible to track cells on bright field microscopy images with image analysis routines implemented in an open-source cell tracking program, PACT (Program for Automated Cell Tracking). We compare the automated motility analysis of three cell tracking programs, PACT, Autozell, and TLA, using the same movies as input for all three programs. We find that different programs track overlapping, but different subsets of cells due to different segmentation methods. Unfortunately, population averages based on such different cell populations, differ significantly in some cases. Thus, results obtained with one software package are not necessarily reproducible by other software. PMID:24688640

MRI mediated, non-invasive tracking of intratumoral distribution of nanocarriers in rat glioma

NASA Astrophysics Data System (ADS)

Karathanasis, Efstathios; Park, Jaekeun; Agarwal, Abhiruchi; Patel, Vijal; Zhao, Fuqiang; Annapragada, Ananth V.; Hu, Xiaoping; Bellamkonda, Ravi V.

2008-08-01

Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection.

MRI mediated, non-invasive tracking of intratumoral distribution of nanocarriers in rat glioma.

PubMed

Karathanasis, Efstathios; Park, Jaekeun; Agarwal, Abhiruchi; Patel, Vijal; Zhao, Fuqiang; Annapragada, Ananth V; Hu, Xiaoping; Bellamkonda, Ravi V

2008-08-06

Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection.

Tensor-based tracking of the aorta in phase-contrast MR images

NASA Astrophysics Data System (ADS)

Azad, Yoo-Jin; Malsam, Anton; Ley, Sebastian; Rengier, Fabian; Dillmann, Rüdiger; Unterhinninghofen, Roland

2014-03-01

The velocity-encoded magnetic resonance imaging (PC-MRI) is a valuable technique to measure the blood flow velocity in terms of time-resolved 3D vector fields. For diagnosis, presurgical planning and therapy control monitoring the patient's hemodynamic situation is crucial. Hence, an accurate and robust segmentation of the diseased vessel is the basis for further methods like the computation of the blood pressure. In the literature, there exist some approaches to transfer the methods of processing DT-MR images to PC-MR data, but the potential of this approach is not fully exploited yet. In this paper, we present a method to extract the centerline of the aorta in PC-MR images by applying methods from the DT-MRI. On account of this, in the first step the velocity vector fields are converted into tensor fields. In the next step tensor-based features are derived and by applying a modified tensorline algorithm the tracking of the vessel course is accomplished. The method only uses features derived from the tensor imaging without the use of additional morphology information. For evaluation purposes we applied our method to 4 volunteer as well as 26 clinical patient datasets with good results. In 29 of 30 cases our algorithm accomplished to extract the vessel centerline.

Radiotherapy beyond cancer: Target localization in real-time MRI and treatment planning for cardiac radiosurgery

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

Ipsen, S.; Blanck, O.; Rades, D.

2014-12-15

Purpose: Atrial fibrillation (AFib) is the most common cardiac arrhythmia that affects millions of patients world-wide. AFib is usually treated with minimally invasive, time consuming catheter ablation techniques. While recently noninvasive radiosurgery to the pulmonary vein antrum (PVA) in the left atrium has been proposed for AFib treatment, precise target location during treatment is challenging due to complex respiratory and cardiac motion. A MRI linear accelerator (MRI-Linac) could solve the problems of motion tracking and compensation using real-time image guidance. In this study, the authors quantified target motion ranges on cardiac magnetic resonance imaging (MRI) and analyzed the dosimetric benefitsmore » of margin reduction assuming real-time motion compensation was applied. Methods: For the imaging study, six human subjects underwent real-time cardiac MRI under free breathing. The target motion was analyzed retrospectively using a template matching algorithm. The planning study was conducted on a CT of an AFib patient with a centrally located esophagus undergoing catheter ablation, representing an ideal case for cardiac radiosurgery. The target definition was similar to the ablation lesions at the PVA created during catheter treatment. Safety margins of 0 mm (perfect tracking) to 8 mm (untracked respiratory motion) were added to the target, defining the planning target volume (PTV). For each margin, a 30 Gy single fraction IMRT plan was generated. Additionally, the influence of 1 and 3 T magnetic fields on the treatment beam delivery was simulated using Monte Carlo calculations to determine the dosimetric impact of MRI guidance for two different Linac positions. Results: Real-time cardiac MRI showed mean respiratory target motion of 10.2 mm (superior–inferior), 2.4 mm (anterior–posterior), and 2 mm (left–right). The planning study showed that increasing safety margins to encompass untracked respiratory motion leads to overlapping structures even in the ideal scenario, compromising either normal tissue dose constraints or PTV coverage. The magnetic field caused a slight increase in the PTV dose with the in-line MRI-Linac configuration. Conclusions: The authors’ results indicate that real-time tracking and motion compensation are mandatory for cardiac radiosurgery and MRI-guidance is feasible, opening the possibility of treating cardiac arrhythmia patients completely noninvasively.« less

Imaging mesenchymal stem cells containing single wall nanotube nanoprobes in a 3D scaffold using photo-thermal optical coherence tomography

NASA Astrophysics Data System (ADS)

Connolly, Emma; Subhash, Hrebesh M.; Leahy, Martin; Rooney, Niall; Barry, Frank; Murphy, Mary; Barron, Valerie

2014-02-01

Despite the fact, that a range of clinically viable imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), photo emission tomography (PET), ultrasound and bioluminescence imaging are being optimised to track cells in vivo, many of these techniques are subject to limitations such as the levels of contrast agent required, toxic effects of radiotracers, photo attenuation of tissue and backscatter. With the advent of nanotechnology, nanoprobes are leading the charge to overcome these limitations. In particular, single wall nanotubes (SWNT) have been shown to be taken up by cells and as such are effective nanoprobes for cell imaging. Consequently, the main aim of this research is to employ mesenchymal stem cells (MSC) containing SWNT nanoprobes to image cell distribution in a 3D scaffold for cartilage repair. To this end, MSC were cultured in the presence of 32μg/ml SWNT in cell culture medium (αMEM, 10% FBS, 1% penicillin/streptomycin) for 24 hours. Upon confirmation of cell viability, the MSC containing SWNT were encapsulated in hyaluronic acid gels and loaded on polylactic acid polycaprolactone scaffolds. After 28 days in complete chondrogenic medium, with medium changes every 2 days, chondrogenesis was confirmed by the presence of glycosaminoglycan. Moreover, using photothermal optical coherence tomography (PT-OCT), the cells were seen to be distributed through the scaffold with high resolution. In summary, these data reveal that MSC containing SWNT nanoprobes in combination with PT-OCT offer an exciting opportunity for stem cell tracking in vitro for assessing seeding scaffolds and in vivo for determining biodistribution.

Safety and efficacy of cardiopoietic stem cells in the treatment of post-infarction left-ventricular dysfunction - From cardioprotection to functional repair in a translational pig infarction model.

PubMed

Emmert, Maximilian Y; Wolint, Petra; Jakab, Andras; Sheehy, Sean P; Pasqualini, Francesco S; Nguyen, Thi Dan Linh; Hilbe, Monika; Seifert, Burkhardt; Weber, Benedikt; Brokopp, Chad E; Macejovska, Dominika; Caliskan, Etem; von Eckardstein, Arnold; Schwartlander, Ruth; Vogel, Viola; Falk, Volkmar; Parker, Kevin Kit; Gyöngyösi, Mariann; Hoerstrup, Simon P

2017-04-01

To date, clinical success of cardiac cell-therapies remains limited. To enhance the cardioreparative properties of stem cells, the concept of lineage-specification through cardiopoietic-guidance has been recently suggested. However, so far, only results from murine studies and from a clinical pilot-trial in chronic heart-failure (CHF) are available, while systematic evidence of its therapeutic-efficacy is still lacking. Importantly, also no data from large animals or for other indications are available. Therefore, we here investigate the therapeutic-efficacy of human cardiopoietic stem cells in the treatment of post-infarction LV-dysfunction using a translational pig-model. Using growth-factor priming, lineage-specification of human bone-marrow derived MSCs was achieved to generate cardiopoietic stem cells according to GMP-compliant protocols. Thereafter, pigs with post-infarction LV-dysfunction (sub-acute phase;1-month) were randomized to either receive transcatheter NOGA 3D electromechanical-mapping guided intramyocardial transplantation of cardiopoietic cells or saline (control). After 30days, cardiac MRI (cMRI) was performed for functional evaluation and in-vivo cell-tracking. This approach was coupled with a comprehensive post-mortem cell-fate and mode-of-repair analysis. Cardiopoietic cell therapy was safe and ejection-fraction was significantly higher when compared to controls (p = 0.012). It further prevented maladaptive LV-remodeling and revealed a significantly lower relative and total infarct-size (p = 0.043 and p = 0.012). As in-vivo tracking and post-mortem analysis displayed only limited intramyocardial cardiopoietic cell-integration, the significant induction of neo-angiogenesis (∼40% higher; p = 0.003) and recruitment of endogenous progenitors (∼2.5x higher; p = 0.008) to the infarct border-zone appeared to be the major modes-of-repair. This is the first report using a pre-clinical large animal-model to demonstrate the safety and efficacy of cardiopoietic stem cells for the treatment of post-infarction LV-dysfunction to prevent negative LV-remodeling and subsequent CHF. It further provides insight into post-delivery cardiopoietic cell-fate and suggests the mechanisms of cardiopoietic cell-induced cardiac-repair. The adoption of GMP-/GLP-compliant methodologies may accelerate the translation into a phase-I clinical-trial in patients with post-ischemic LV-dysfunction broadening the current indication of this interesting cell-type. Copyright © 2016. Published by Elsevier Ltd.

DTI fiber tracking to differentiate demyelinating diseases from diffuse brain stem glioma.

PubMed

Giussani, Carlo; Poliakov, Andrew; Ferri, Raymond T; Plawner, Lauren L; Browd, Samuel R; Shaw, Dennis W W; Filardi, Tanya Z; Hoeppner, Corrine; Geyer, J Russell; Olson, James M; Douglas, James G; Villavicencio, Elisabeth H; Ellenbogen, Richard G; Ojemann, Jeffrey G

2010-08-01

Intrinsic diffuse brainstem tumors and demyelinating diseases primarily affecting the brainstem can share common clinical and radiological features, sometimes making the diagnosis difficult especially at the time of first clinical presentation. To explore the potential usefulness of new MRI sequences in particular diffusion tensor imaging fiber tracking in differentiating these two pathological entities, we review a series of brainstem tumors and demyelinating diseases treated at our institution. The clinical history including signs and symptoms and MRI findings of three consecutive demyelinating diseases involving the brainstem that presented with diagnostic uncertainty and three diffuse intrinsic brainstem tumors were reviewed, along with a child with a supratentorial tumor for comparison. Fiber tracking of the pyramidal tracts was performed for each patient using a DTI study at the time of presentation. Additionally Fractional Anisotropy values were calculated for each patient in the pons and the medulla oblongata. Routine MR imaging was unhelpful in differentiating between intrinsic tumor and demyelination. In contrast, retrospective DTI fiber tracking clearly differentiated the pathology showing deflection of the pyramidal tracts posteriorly and laterally in the case of intrinsic brainstem tumors and, in the case of demyelinating disease, poorly represented and truncated fibers. Regionalized FA values were variable and of themselves were not predictive either pathology. DTI fiber tracking of the pyramid tracts in patients with suspected intrinsic brainstem tumor or demyelinating disease presents two clearly different patterns that may help in differentiating between these two pathologies when conventional MRI and clinical data are inconclusive. Copyright 2010 Elsevier Inc. All rights reserved.

Anomaly detection driven active learning for identifying suspicious tracks and events in WAMI video

NASA Astrophysics Data System (ADS)

Miller, David J.; Natraj, Aditya; Hockenbury, Ryler; Dunn, Katherine; Sheffler, Michael; Sullivan, Kevin

2012-06-01

We describe a comprehensive system for learning to identify suspicious vehicle tracks from wide-area motion (WAMI) video. First, since the road network for the scene of interest is assumed unknown, agglomerative hierarchical clustering is applied to all spatial vehicle measurements, resulting in spatial cells that largely capture individual road segments. Next, for each track, both at the cell (speed, acceleration, azimuth) and track (range, total distance, duration) levels, extreme value feature statistics are both computed and aggregated, to form summary (p-value based) anomaly statistics for each track. Here, to fairly evaluate tracks that travel across different numbers of spatial cells, for each cell-level feature type, a single (most extreme) statistic is chosen, over all cells traveled. Finally, a novel active learning paradigm, applied to a (logistic regression) track classifier, is invoked to learn to distinguish suspicious from merely anomalous tracks, starting from anomaly-ranked track prioritization, with ground-truth labeling by a human operator. This system has been applied to WAMI video data (ARGUS), with the tracks automatically extracted by a system developed in-house at Toyon Research Corporation. Our system gives promising preliminary results in highly ranking as suspicious aerial vehicles, dismounts, and traffic violators, and in learning which features are most indicative of suspicious tracks.

A cCPE-based xenon biosensor for magnetic resonance imaging of claudin-expressing cells.

PubMed

Piontek, Anna; Witte, Christopher; May Rose, Honor; Eichner, Miriam; Protze, Jonas; Krause, Gerd; Piontek, Jörg; Schröder, Leif

2017-06-01

The majority of malignant tumors originate from epithelial cells, and many of them are characterized by an overexpression of claudins (Cldns) and their mislocalization out of tight junctions. We utilized the C-terminal claudin-binding domain of Clostridium perfringens enterotoxin (cCPE), with its high affinity to specific members of the claudin family, as the targeting unit for a claudin-sensitive cancer biosensor. To overcome the poor sensitivity of conventional relaxivity-based magnetic resonance imaging (MRI) contrast agents, we utilized the superior sensitivity of xenon Hyper-CEST biosensors. We labeled cCPE for both xenon MRI and fluorescence detection. As one readout module, we employed a cryptophane (CrA) monoacid and, as the second, a fluorescein molecule. Both were conjugated separately to a biotin molecule via a polyethyleneglycol chemical spacer and later via avidin linked to GST-cCPE. Nontransfected HEK293 cells and HEK293 cells stably expressing Cldn4-FLAG were incubated with the cCPE-based biosensor. Fluorescence-based flow cytometry and xenon MRI demonstrated binding of the biosensor specifically to Cldn4-expressing cells. This study provides proof of concept for the use of cCPE as a carrier for diagnostic contrast agents, a novel approach for potential detection of Cldn3/-4-overexpressing tumors for noninvasive early cancer detection. © 2017 New York Academy of Sciences.

Design Method of Digital Optimal Control Scheme and Multiple Paralleled Bridge Type Current Amplifier for Generating Gradient Magnetic Fields in MRI Systems

NASA Astrophysics Data System (ADS)

Watanabe, Shuji; Takano, Hiroshi; Fukuda, Hiroya; Hiraki, Eiji; Nakaoka, Mutsuo

This paper deals with a digital control scheme of multiple paralleled high frequency switching current amplifier with four-quadrant chopper for generating gradient magnetic fields in MRI (Magnetic Resonance Imaging) systems. In order to track high precise current pattern in Gradient Coils (GC), the proposal current amplifier cancels the switching current ripples in GC with each other and designed optimum switching gate pulse patterns without influences of the large filter current ripple amplitude. The optimal control implementation and the linear control theory in GC current amplifiers have affinity to each other with excellent characteristics. The digital control system can be realized easily through the digital control implementation, DSPs or microprocessors. Multiple-parallel operational microprocessors realize two or higher paralleled GC current pattern tracking amplifier with optimal control design and excellent results are given for improving the image quality of MRI systems.

Tracking Adult Literacy Acquisition with Functional MRI: A Single-Case Study

ERIC Educational Resources Information Center

Braga, Lucia W.; Amemiya, Eduardo; Tauil, Alexandre; Suguieda, Denis; Lacerda, Carolina; Klein, Elise; Dehaene-Lambertz, Ghislaine; Dehaene, Stanislas

2017-01-01

We evaluated neuro-functional changes associated with late acquisition of reading in an illiterate adult who underwent 20 longitudinal functional magnetic resonance imaging (fMRI) scans during 2 years, while the participant progressed from complete illiteracy to a modest level of alphabetical decoding. Initially, the participant did not activate…

MRI with DWI for the Detection of Posttreatment Head and Neck Squamous Cell Carcinoma: Why Morphologic MRI Criteria Matter.

PubMed

Ailianou, A; Mundada, P; De Perrot, T; Pusztaszieri, M; Poletti, P-A; Becker, M

2018-04-01

Although diffusion-weighted imaging combined with morphologic MRI (DWIMRI) is used to detect posttreatment recurrent and second primary head and neck squamous cell carcinoma, the diagnostic criteria used so far have not been clarified. We hypothesized that precise MRI criteria based on signal intensity patterns on T2 and contrast-enhanced T1 complement DWI and therefore improve the diagnostic performance of DWIMRI. We analyzed 1.5T MRI examinations of 100 consecutive patients treated with radiation therapy with or without additional surgery for head and neck squamous cell carcinoma. MRI examinations included morphologic sequences and DWI ( b =0 and b =1000 s/mm 2 ). Histology and follow-up served as the standard of reference. Two experienced readers, blinded to clinical/histologic/follow-up data, evaluated images according to clearly defined criteria for the diagnosis of recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment, post-radiation therapy inflammatory edema, and late fibrosis. DWI analysis included qualitative (visual) and quantitative evaluation with an ADC threshold. Recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment was present in 36 patients, whereas 64 patients had post-radiation therapy lesions only. The Cohen κ for differentiating tumor from post-radiation therapy lesions with MRI and qualitative DWIMRI was 0.822 and 0.881, respectively. Mean ADCmean in recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment (1.097 ± 0.295 × 10 -3 mm 2 /s) was significantly lower ( P < .05) than in post-radiation therapy inflammatory edema (1.754 ± 0.343 × 10 -3 mm 2 /s); however, it was similar to that in late fibrosis (0.987 ± 0.264 × 10 -3 mm 2 /s, P > .05). Although ADCs were similar in tumors and late fibrosis, morphologic MRI criteria facilitated distinction between the 2 conditions. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (95% CI) of DWIMRI with ADCmean < 1.22 × 10 -3 mm 2 /s and precise MRI criteria were 92.1% (83.5-100.0), 95.4% (90.3-100.0), 92.1% (83.5-100.0), 95.4% (90.2-100.0), 19.9 (6.58-60.5), and 0.08 (0.03-0.24), respectively, indicating a good diagnostic performance to rule in and rule out disease. Adding precise morphologic MRI criteria to quantitative DWI enables reproducible and accurate detection of recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment. © 2018 by American Journal of Neuroradiology.

Imaging vulnerable plaques by targeting inflammation in atherosclerosis using fluorescent-labeled dual-ligand microparticles of iron oxide and magnetic resonance imaging.

PubMed

Chan, Joyce M S; Monaco, Claudia; Wylezinska-Arridge, Marzena; Tremoleda, Jordi L; Cole, Jennifer E; Goddard, Michael; Cheung, Maggie S H; Bhakoo, Kishore K; Gibbs, Richard G J

2018-05-01

Identification of patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and a prelude to clinical sequelae. There are currently no clinical imaging tools to assess the inflammatory activity within plaques. This study characterized inflammation in atherosclerosis using dual-targeted microparticles of iron oxide (DT-MPIO) as a magnetic resonance imaging (MRI) probe. DT-MPIO were used to detect and characterize inflammatory markers, vascular cell adhesion molecule 1 (VCAM-1). and P-selectin on (1) tumor necrosis factor-α-treated cells by immunocytochemistry and (2) aortic root plaques of apolipoprotein-E deficient mice by in vivo MRI. Furthermore, apolipoprotein E-deficient mice with focal carotid plaques of different phenotypes were developed by means of periarterial cuff placement to allow in vivo molecular MRI using these probes. The association between biomarkers and the magnetic resonance signal in different contrast groups was assessed longitudinally in these models. Immunocytochemistry confirmed specificity and efficacy of DT-MPIO to VCAM-1 and P-selectin. Using this in vivo molecular MRI strategy, we demonstrated (1) the DT-MPIO-induced magnetic resonance signal tracked with VCAM-1 (r = 0.69; P = .014), P-selectin (r = 0.65; P = .022), and macrophage content (r = 0.59; P = .045) within aortic root plaques and (2) high-risk inflamed plaques were distinguished from noninflamed plaques in the murine carotid artery within a practical clinical imaging time frame. These molecular MRI probes constitute a novel imaging tool for in vivo characterization of plaque vulnerability and inflammatory activity in atherosclerosis. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid atherosclerotic disease in the future. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Tracking Organs Composed of One or Multiple Regions Using Geodesic Active Region Models

NASA Astrophysics Data System (ADS)

Martínez, A.; Jiménez, J. J.

In radiotherapy treatment it is very important to find out the target organs on the medical image sequence in order to determine and apply the proper dose. The techniques to achieve this goal can be classified into extrinsic and intrinsic. Intrinsic techniques only use image processing with medical images associated to the radiotherapy treatment, as we deal in this chapter. To accurately perform this organ tracking it is necessary to find out segmentation and tracking models that were able to be applied to several image modalities involved on a radiotherapy session (CT See Modality , MRI , etc.). The movements of the organs are mainly affected by two factors: breathing and involuntary movements associated with the internal organs or patient positioning. Among the several alternatives to track the organs of interest, a model based on geodesic active regions is proposed. This model has been tested over CT images from the pelvic, cardiac, and thoracic area. A new model for the segmentation of organs composed by more than one region is proposed.

DW-MRI as a Predictive Biomarker of Radiosensitization of GBM through Targeted Inhibition of Checkpoint Kinases.

PubMed

Williams, Terence M; Galbán, Stefanie; Li, Fei; Heist, Kevin A; Galbán, Craig J; Lawrence, Theodore S; Holland, Eric C; Thomae, Tami L; Chenevert, Thomas L; Rehemtulla, Alnawaz; Ross, Brian D

2013-04-01

The inherent treatment resistance of glioblastoma (GBM) can involve multiple mechanisms including checkpoint kinase (Chk1/2)-mediated increased DNA repair capability, which can attenuate the effects of genotoxic chemotherapies and radiation. The goal of this study was to evaluate diffusion-weighted magnetic resonance imaging (DW-MRI) as a biomarker for Chk1/2 inhibitors in combination with radiation for enhancement of treatment efficacy in GBM. We evaluated a specific small molecule inhibitor of Chk1/2, AZD7762, in combination with radiation using in vitro human cell lines and in vivo using a genetically engineered GBM mouse model. DW-MRI and T1-contrast MRI were used to follow treatment effects on intracranial tumor cellularity and growth rates, respectively. AZD7762 inhibited clonal proliferation in a panel of GBM cell lines and increased radiosensitivity in p53-mutated GBM cell lines to a greater extent compared to p53 wild-type cells. In vivo efficacy of AZD7762 demonstrated a dose-dependent inhibitory effect on GBM tumor growth rate and a reduction in tumor cellularity based on DW-MRI scans along with enhancement of radiation efficacy. DW-MRI was found to be a useful imaging biomarker for the detection of radiosensitization through inhibition of checkpoint kinases. Chk1/2 inhibition resulted in antiproliferative activity, prevention of DNA damage-induced repair, and radiosensitization in preclinical GBM tumor models, both in vitro and in vivo. The effects were found to be maximal in p53-mutated GBM cells. These results provide the rationale for integration of DW-MRI in clinical translation of Chk1/2 inhibition with radiation for the treatment of GBM.

Measuring the lesion load of multiple sclerosis patients within the corticospinal tract

NASA Astrophysics Data System (ADS)

Klein, Jan; Hanken, Katrin; Koceva, Jasna; Hildebrandt, Helmut; Hahn, Horst K.

2015-03-01

In this paper we present a framework for reliable determination of the lesion load within the corticospinal tract (CST) of multiple sclerosis patients. The basis constitutes a probabilistic fiber tracking approach which checks possible parameter intervals on the fly using an anatomical brain atlas. By exploiting the range of those intervals, the algorithm is able to resolve fiber crossings and to determine the CST in its full entity although it can use a simple diffusion tensor model. Another advantage is its short running time, tracking the CST takes less than a minute. For segmenting the lesions we developed a semi-automatic approach. First, a trained classifier is applied to multimodal MRI data (T1/FLAIR) where the spectrum of lesions has been determined in advance by a clustering algorithm. This leads to an automatic detection of the lesions which can be manually corrected afterwards using a threshold-based approach. For evaluation we scanned 46 MS patients and 16 healthy controls. Fiber tracking has been performed using our novel fiber tracking and a standard defection based algorithm. Regression analysis of the old and new version of the algorithm showed a highly significant superiority of the new algorithm for disease duration. Additionally, a low correlation between old and new approach supports the observation that standard DTI fiber tracking is not always able to track and quantify the CST reliably.

Non-invasive high-resolution tracking of human neuronal pathways: diffusion tensor imaging at 7T with 1.2 mm isotropic voxel size

NASA Astrophysics Data System (ADS)

Lützkendorf, Ralf; Hertel, Frank; Heidemann, Robin; Thiel, Andreas; Luchtmann, Michael; Plaumann, Markus; Stadler, Jörg; Baecke, Sebastian; Bernarding, Johannes

2013-03-01

Diffusion tensor imaging (DTI) allows characterizing and exploiting diffusion anisotropy effects, thereby providing important details about tissue microstructure. A major application in neuroimaging is the so-called fiber tracking where neuronal connections between brain regions are determined non-invasively by DTI. Combining these neural pathways within the human brain with the localization of activated brain areas provided by functional MRI offers important information about functional connectivity of brain regions. However, DTI suffers from severe signal reduction due to the diffusion-weighting. Ultra-high field (UHF) magnetic resonance imaging (MRI) should therefore be advantageous to increase the intrinsic signal-to-noise ratio (SNR). This in turn enables to acquire high quality data with increased resolution, which is beneficial for tracking more complex fiber structures. However, UHF MRI imposes some difficulties mainly due to the larger B1 inhomogeneity compared to 3T MRI. We therefore optimized the parameters to perform DTI at a 7 Tesla whole body MR scanner equipped with a high performance gradient system and a 32-channel head receive coil. A Stesjkal Tanner spin-echo EPI sequence was used, to acquire 110 slices with an isotropic voxel-size of 1.2 mm covering the whole brain. 60 diffusion directions were scanned which allows calculating the principal direction components of the diffusion vector in each voxel. The results prove that DTI can be performed with high quality at UHF and that it is possible to explore the SNT benefit of the higher field strength. Combining UHF fMRI data with UHF DTI results will therefore be a major step towards better neuroimaging methods.

Retrospective respiratory self-gating and removal of bulk motion in pulmonary UTE MRI of neonates and adults.

PubMed

Higano, Nara S; Hahn, Andrew D; Tkach, Jean A; Cao, Xuefeng; Walkup, Laura L; Thomen, Robert P; Merhar, Stephanie L; Kingma, Paul S; Fain, Sean B; Woods, Jason C

2017-03-01

To implement pulmonary three-dimensional (3D) radial ultrashort echo-time (UTE) MRI in non-sedated, free-breathing neonates and adults with retrospective motion tracking of respiratory and intermittent bulk motion, to obtain diagnostic-quality, respiratory-gated images. Pulmonary 3D radial UTE MRI was performed at 1.5 tesla (T) during free breathing in neonates and adult volunteers for validation. Motion-tracking waveforms were obtained from the time course of each free induction decay's initial point (i.e., k-space center), allowing for respiratory-gated image reconstructions that excluded data acquired during bulk motion. Tidal volumes were calculated from end-expiration and end-inspiration images. Respiratory rates were calculated from the Fourier transform of the motion-tracking waveform during quiet breathing, with comparison to physiologic prediction in neonates and validation with spirometry in adults. High-quality respiratory-gated anatomic images were obtained at inspiration and expiration, with less respiratory blurring at the expense of signal-to-noise for narrower gating windows. Inspiration-expiration volume differences agreed with physiologic predictions (neonates; Bland-Altman bias = 6.2 mL) and spirometric values (adults; bias = 0.11 L). MRI-measured respiratory rates compared well with the observed rates (biases = -0.5 and 0.2 breaths/min for neonates and adults, respectively). Three-dimensional radial pulmonary UTE MRI allows for retrospective respiratory self-gating and removal of intermittent bulk motion in free-breathing, non-sedated neonates and adults. Magn Reson Med 77:1284-1295, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking imaging.

PubMed

Notomi, Yuichi; Lysyansky, Peter; Setser, Randolph M; Shiota, Takahiro; Popović, Zoran B; Martin-Miklovic, Maureen G; Weaver, Joan A; Oryszak, Stephanie J; Greenberg, Neil L; White, Richard D; Thomas, James D

2005-06-21

We sought to examine the accuracy/consistency of a novel ultrasound speckle tracking imaging (STI) method for left ventricular torsion (LVtor) measurement in comparison with tagged magnetic resonance imaging (MRI) (a time-domain method similar to STI) and Doppler tissue imaging (DTI) (a velocity-based approach). Left ventricular torsion from helically oriented myofibers is a key parameter of cardiac performance but is difficult to measure. Ultrasound STI is potentially suitable for measurement of angular motion because of its angle-independence. We acquired basal and apical short-axis left ventricular (LV) images in 15 patients to estimate LVtor by STI and compare it with tagged MRI and DTI. Left ventricular torsion was defined as the net difference of LV rotation at the basal and apical planes. For the STI analysis, we used high-frame (104 +/- 12 frames/s) second harmonic two-dimensional images. Data on 13 of 15 patients were usable for STI analysis, and LVtor profile estimated by STI strongly correlated with those by tagged MRI (y = 0.95x + 0.19, r = 0.93, p < 0.0001, analyzed by repeated-measures regression models). The STI torsional velocity profile also correlated well with that by the DTI method (y = 0.79x + 2.4, r = 0.76, p < 0.0001, by repeated-measures regression models) with acceptable bias. The STI estimation of LVtor is concordant with those analyzed by tagged MRI (data derived from tissue displacement) and also showed good agreement with those by DTI (data derived from tissue velocity). Ultrasound STI is a promising new method to assess LV torsional deformation and may make the assessment more available in clinical and research cardiology.

Autonomous Navigation Performance During The Hartley 2 Comet Flyby

NASA Technical Reports Server (NTRS)

Abrahamson, Matthew J; Kennedy, Brian A.; Bhaskaran, Shyam

2012-01-01

On November 4, 2010, the EPOXI spacecraft performed a 700-km flyby of the comet Hartley 2 as follow-on to the successful 2005 Deep Impact prime mission. EPOXI, an extended mission for the Deep Impact Flyby spacecraft, returned a wealth of visual and infrared data from Hartley 2, marking the fifth time that high-resolution images of a cometary nucleus have been captured by a spacecraft. The highest resolution science return, captured at closest approach to the comet nucleus, was enabled by use of an onboard autonomous navigation system called AutoNav. AutoNav estimates the comet-relative spacecraft trajectory using optical measurements from the Medium Resolution Imager (MRI) and provides this relative position information to the Attitude Determination and Control System (ADCS) for maintaining instrument pointing on the comet. For the EPOXI mission, AutoNav was tasked to enable continuous tracking of a smaller, more active Hartley 2, as compared to Tempel 1, through the full encounter while traveling at a higher velocity. To meet the mission goal of capturing the comet in all MRI science images, position knowledge accuracies of +/- 3.5 km (3-?) cross track and +/- 0.3 seconds (3-?) time of flight were required. A flight-code-in-the-loop Monte Carlo simulation assessed AutoNav's statistical performance under the Hartley 2 flyby dynamics and determined optimal configuration. The AutoNav performance at Hartley 2 was successful, capturing the comet in all of the MRI images. The maximum residual between observed and predicted comet locations was 20 MRI pixels, primarily influenced by the center of brightness offset from the center of mass in the observations and attitude knowledge errors. This paper discusses the Monte Carlo-based analysis that led to the final AutoNav configuration and a comparison of the predicted performance with the flyby performance.

In vitro labelling and detection of mesenchymal stromal cells: a comparison between magnetic resonance imaging of iron-labelled cells and magnetic resonance spectroscopy of fluorine-labelled cells.

PubMed

Rizzo, Stefania; Petrella, Francesco; Zucca, Ileana; Rinaldi, Elena; Barbaglia, Andrea; Padelli, Francesco; Baggi, Fulvio; Spaggiari, Lorenzo; Bellomi, Massimo; Bruzzone, Maria Grazia

2017-01-01

Among the various stem cell populations used for cell therapy, adult mesenchymal stromal cells (MSCs) have emerged as a major new cell technology. These cells must be tracked after transplantation to monitor their migration within the body and quantify their accumulation at the target site. This study assessed whether rat bone marrow MSCs can be labelled with superparamagnetic iron oxide (SPIO) nanoparticles and perfluorocarbon (PFC) nanoemulsion formulations without altering cell viability and compared magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) results from iron-labelled and fluorine-labelled MSCs, respectively. Of MSCs, 2 × 10 6 were labelled with Molday ION Rhodamine-B (MIRB) and 2 × 10 6 were labelled with Cell Sense. Cell viability was evaluated by trypan blue exclusion method. Labelled MSCs were divided into four samples containing increasing cell numbers (0.125 × 10 6 , 0.25 × 10 6 , 0.5 × 10 6 , 1 × 10 6 ) and scanned on a 7T MRI: for MIRB-labelled cells, phantoms and cells negative control, T1, T2 and T2* maps were acquired; for Cell Sense labelled cells, phantoms and unlabelled cells, a 19 F non-localised single-pulse MRS sequence was acquired. In total, 86.8% and 83.6% of MIRB-labelled cells and Cell Sense-labelled cells were viable, respectively. MIRB-labelled cells were visible in all samples with different cell numbers; pellets containing 0.5 × 10 6 and 1 × 10 6 of Cell Sense-labelled cells showed a detectable 19 F signal. Our data support the use of both types of contrast material (SPIO and PFC) for MSCs labelling, although further efforts should be dedicated to improve the efficiency of PFC labelling.

A compact multi-bit flip-flop with smaller height implementation and metal-less intra-cell routing

NASA Astrophysics Data System (ADS)

Seo, Jaewoo; Jung, Jinwook; Shin, Youngsoo

2018-03-01

Multi-bit flip-ops (MBFFs) are widely used in modern circuit designs because of their lower power consumption and smaller footprint. However, conventional MBFFs have routability issues due to the dense intra-cell connections. Since many horizontal connections are populated in the typical MBFF layouts, metal-2 (M2) tracks are highly occupied inside the cell. Accordingly, routers cannot leverage the M2 tracks for inter-cell connections. The conventional MBFFs also show a limited impact on the cell area reduction. Since the cell area saving of an MBFF mainly comes from the clock driver sharing, the layouts of other ip-op modules remain almost the same. In this paper, we propose a compact MBFF with metal-less clock routing and smaller height implementation. To achieve a sparse population of M2 routing tracks, we vertically place MBFF modules and interconnect them using the poly layer. As a result, the wire length of M2 layer inside a cell is significantly reduced. We also propose the smaller cell height implementation for compact MBFF layouts. Assuming the default standard cell height of 9 tracks, we present a 6-track MBFF implementation and the glue logic which makes legal cell placement with the 9-track logic cells. Experiments with a few test circuits show that the number of routing grids having congestion overflow is reduced by 16% and 73%, on average, compared to the single-bit flip-op and conventional MBFF based designs, respectively. Total cell area is also reduced by 8% and 2%, on average, compared to the single-bit flip-op and conventional MBFF based designs, respectively.

Labeling Human Mesenchymal Stem Cells with Gold Nanocages for in vitro and in vivo Tracking by Two-Photon Microscopy and Photoacoustic Microscopy

PubMed Central

Zhang, Yu Shrike; Wang, Yu; Wang, Lidai; Wang, Yucai; Cai, Xin; Zhang, Chi; Wang, Lihong V.; Xia, Younan

2013-01-01

Stem cell tracking is a highly important subject. Current techniques based on nanoparticle-labeling, such as magnetic resonance imaging, fluorescence microscopy, and micro-computed tomography, are plagued by limitations including relatively low sensitivity or penetration depth, involvement of ionizing irradiation, and potential cytotoxicity of the nanoparticles. Here we introduce a new class of contrast agents based on gold nanocages (AuNCs) with hollow interiors and porous walls to label human mesenchymal stem cells (hMSCs) for both in vitro and in vivo tracking using two-photon microscopy and photoacoustic microscopy. As demonstrated by the viability assay, the AuNCs showed negligible cytotoxicity under a reasonable dose, and did not alter the differentiation potential of the hMSCs into desired lineages. We were able to image the cells labeled with AuNCs in vitro for at least 28 days in culture, as well as to track the cells that homed to the tumor region in nude mice in vivo. PMID:23946820

Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) for the assessment of Pc 4-sensitized photodynamic therapy of a U87-derived glioma model in the athymic nude rat

NASA Astrophysics Data System (ADS)

Anka, Ali; Thompson, Paul; Mott, Eric; Sharma, Rahul; Zhang, Ruozhen; Cross, Nathan; Sun, Jiayang; Flask, Chris A.; Oleinick, Nancy L.; Dean, David

2010-02-01

Introduction: Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) may provide a means of tracking the outcome of Pc 4-sensitized photodynamic therapy (PDT) in deeply placed lesions (e.g., brain tumors). We previously determined that 150 μL of gadolinium (Gd-DTPA) produces optimal enhancement of U87-derived intracerebral tumors in an athymic nude rat glioma model. We wish to determine how consistently DCE-MRI enhancement will detect an increase in Gd-enhancement of these tumors following Pc 4-PDT. Methods: We injected 2.5 x 105 U87 cells into the brains of 6 athymic nude rats. After 7-8 days pre-Pc 4 PDT peri-tumor DCE-MRI images were acquired on a 7.0T microMRI scanner before and after administration of 150 μL Gd. DCE-MRI scans were repeated on Days 11, 12, and 13 following Pc 4-PDT (Day 8 or 9). Results: Useful DCE-MRI data were obtained for these animals before and after Pc 4- PDT. In the pre-Pc 4-PDT DCE-MRI scans an average normalized peak Gd enhancement was observed in tumor tissue that was 1.297 times greater than baseline (0.035 Standard Error [SE]). The average normalized peak Gd enhancement in the tumor tissue in the scan following PDT (Day 11) was 1.537 times greater than baseline (0.036 SE), a statistically significant increase in enhancement (p = 0.00584) over the pre-PDT level. Discussion: A 150 μL Gd dose appears to provide an unambiguous increase in signal indicating Pc 4-PDT-induced necrosis of the U87-derived tumor. Our DCEMRI protocol may allow the development of a clinically robust, unambiguous, non-invasive technique for the assessment of PDT outcome.

Probabilistic vs. deterministic fiber tracking and the influence of different seed regions to delineate cerebellar-thalamic fibers in deep brain stimulation.

PubMed

Schlaier, Juergen R; Beer, Anton L; Faltermeier, Rupert; Fellner, Claudia; Steib, Kathrin; Lange, Max; Greenlee, Mark W; Brawanski, Alexander T; Anthofer, Judith M

2017-06-01

This study compared tractography approaches for identifying cerebellar-thalamic fiber bundles relevant to planning target sites for deep brain stimulation (DBS). In particular, probabilistic and deterministic tracking of the dentate-rubro-thalamic tract (DRTT) and differences between the spatial courses of the DRTT and the cerebello-thalamo-cortical (CTC) tract were compared. Six patients with movement disorders were examined by magnetic resonance imaging (MRI), including two sets of diffusion-weighted images (12 and 64 directions). Probabilistic and deterministic tractography was applied on each diffusion-weighted dataset to delineate the DRTT. Results were compared with regard to their sensitivity in revealing the DRTT and additional fiber tracts and processing time. Two sets of regions-of-interests (ROIs) guided deterministic tractography of the DRTT or the CTC, respectively. Tract distances to an atlas-based reference target were compared. Probabilistic fiber tracking with 64 orientations detected the DRTT in all twelve hemispheres. Deterministic tracking detected the DRTT in nine (12 directions) and in only two (64 directions) hemispheres. Probabilistic tracking was more sensitive in detecting additional fibers (e.g. ansa lenticularis and medial forebrain bundle) than deterministic tracking. Probabilistic tracking lasted substantially longer than deterministic. Deterministic tracking was more sensitive in detecting the CTC than the DRTT. CTC tracts were located adjacent but consistently more posterior to DRTT tracts. These results suggest that probabilistic tracking is more sensitive and robust in detecting the DRTT but harder to implement than deterministic approaches. Although sensitivity of deterministic tracking is higher for the CTC than the DRTT, targets for DBS based on these tracts likely differ. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease.

PubMed

Case, Michelle; Zhang, Huishi; Mundahl, John; Datta, Yvonne; Nelson, Stephen; Gupta, Kalpna; He, Bin

2017-01-01

Sickle cell disease (SCD) is a red blood cell disorder that causes many complications including life-long pain. Treatment of pain remains challenging due to a poor understanding of the mechanisms and limitations to characterize and quantify pain. In the present study, we examined simultaneously recording functional MRI (fMRI) and electroencephalogram (EEG) to better understand neural connectivity as a consequence of chronic pain in SCD patients. We performed independent component analysis and seed-based connectivity on fMRI data. Spontaneous power and microstate analysis was performed on EEG-fMRI data. ICA analysis showed that patients lacked activity in the default mode network (DMN) and executive control network compared to controls. EEG-fMRI data revealed that the insula cortex's role in salience increases with age in patients. EEG microstate analysis showed patients had increased activity in pain processing regions. The cerebellum in patients showed a stronger connection to the periaqueductal gray matter (involved in pain inhibition), and negative connections to pain processing areas. These results suggest that patients have reduced activity of DMN and increased activity in pain processing regions during rest. The present findings suggest resting state connectivity differences between patients and controls can be used as novel biomarkers of SCD pain.

Toward a comprehensive hybrid physical-virtual reality simulator of peripheral anesthesia with ultrasound and neurostimulator guidance.

PubMed

Samosky, Joseph T; Allen, Pete; Boronyak, Steve; Branstetter, Barton; Hein, Steven; Juhas, Mark; Nelson, Douglas A; Orebaugh, Steven; Pinto, Rohan; Smelko, Adam; Thompson, Mitch; Weaver, Robert A

2011-01-01

We are developing a simulator of peripheral nerve block utilizing a mixed-reality approach: the combination of a physical model, an MRI-derived virtual model, mechatronics and spatial tracking. Our design uses tangible (physical) interfaces to simulate surface anatomy, haptic feedback during needle insertion, mechatronic display of muscle twitch corresponding to the specific nerve stimulated, and visual and haptic feedback for the injection syringe. The twitch response is calculated incorporating the sensed output of a real neurostimulator. The virtual model is isomorphic with the physical model and is derived from segmented MRI data. This model provides the subsurface anatomy and, combined with electromagnetic tracking of a sham ultrasound probe and a standard nerve block needle, supports simulated ultrasound display and measurement of needle location and proximity to nerves and vessels. The needle tracking and virtual model also support objective performance metrics of needle targeting technique.

Trans-dimensional MCMC methods for fully automatic motion analysis in tagged MRI.

PubMed

Smal, Ihor; Carranza-Herrezuelo, Noemí; Klein, Stefan; Niessen, Wiro; Meijering, Erik

2011-01-01

Tagged magnetic resonance imaging (tMRI) is a well-known noninvasive method allowing quantitative analysis of regional heart dynamics. Its clinical use has so far been limited, in part due to the lack of robustness and accuracy of existing tag tracking algorithms in dealing with low (and intrinsically time-varying) image quality. In this paper, we propose a novel probabilistic method for tag tracking, implemented by means of Bayesian particle filtering and a trans-dimensional Markov chain Monte Carlo (MCMC) approach, which efficiently combines information about the imaging process and tag appearance with prior knowledge about the heart dynamics obtained by means of non-rigid image registration. Experiments using synthetic image data (with ground truth) and real data (with expert manual annotation) from preclinical (small animal) and clinical (human) studies confirm that the proposed method yields higher consistency, accuracy, and intrinsic tag reliability assessment in comparison with other frequently used tag tracking methods.

TH-AB-BRA-08: Simulated Tumor Tracking in An MRI Linac for Lung Tumor Lesions Using the Monaco Treatment Planning System

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

Al-Ward, S; Kim, A; McCann, C

2016-06-15

Purpose: To simulate tumor tracking in an Elekta MRI-linac (MRL) and to compare this tracking method with our current ITV approach in terms of OAR sparing for lung cancer patients. Methods: Five SABR-NSCLC patients with central lung tumors were selected for reasons of potential enhancement of tumor-tissue delineation using MRI. The Monaco TPS was used to compare the current clinical ITV approach to a simulated, novel tracking method which used a 7MV MRL beam in the presence of an orthogonal 1.5 T magnetic field (4D-MRL method). In the simulated tracking scenario, achieved using the virtual couch shift (VCS), the PTVmore » was defined using an isotropic 5mm margin applied to the GTV of each phase, as acquired from an 8-phase amplitude-binned 4DCT. These VCS plans were optimized and weighted on each phase. The dose weighting was performed using the patient-specific breathing traces. The doses were accumulated on the inhale phase. The two methods were compared by assessing the OAR DVHs. Results: The 4D-MRL method resulted in a reduced target volume (by an average of 29% over all patients). The benefits of using an MRL tracking system depended on the tumor motion amplitude and the relative OAR motion (ROM) to the target. The reduction in mean doses to parallel organs was up to 3 Gy for the heart and 2.1 Gy for the lung. The reductions in maximum doses to serial organs were up to 9.4 Gy, 5.6 Gy, and 8.7 Gy for the esophagus, spinal cord, and the trachea, respectively. Serial organs benefited from MRL tracking when the ROM was ≥ 0.3 cm despite small tumor motion amplitude in some cases. Conclusions: This work demonstrated the potential benefit for an MRL tracking system to spare OARs in SABR-NSCLC patients with central tumors. The benefits are embodied in the target volume reduction. This project was made possible with the financial support of Elekta.« less

Engineering cell-fluorescent ion track hybrid detectors.

PubMed

Niklas, Martin; Greilich, Steffen; Melzig, Claudius; Akselrod, Mark S; Debus, Jürgen; Jäkel, Oliver; Abdollahi, Amir

2013-06-11

The lack of sensitive biocompatible particle track detectors has so far limited parallel detection of physical energy deposition and biological response. Fluorescent nuclear track detectors (FNTDs) based on Al₂O₃:C,Mg single crystals combined with confocal laser scanning microscopy (CLSM) provide 3D information on ion tracks with a resolution limited by light diffraction. Here we report the development of next generation cell-fluorescent ion track hybrid detectors (Cell-Fit-HD). The biocompatibility of FNTDs was tested using six different cell lines, i.e. human non-small cell lung carcinoma (A549), glioblastoma (U87), androgen independent prostate cancer (PC3), epidermoid cancer (A431) and murine (VmDk) glioma SMA-560. To evaluate cell adherence, viability and conformal coverage of the crystals different seeding densities and alternative coating with extracellular matrix (fibronectin) was tested. Carbon irradiation was performed in Bragg peak (initial 270.55 MeV u⁻¹). A series of cell compartment specific fluorescence stains including nuclear (HOECHST), membrane (Glut-1), cytoplasm (Calcein AM, CM-DiI) were tested on Cell-Fit-HDs and a single CLSM was employed to co-detect the physical (crystal) as well as the biological (cell layer) information. The FNTD provides a biocompatible surface. Among the cells tested, A549 cells formed the most uniform, viable, tightly packed epithelial like monolayer. The ion track information was not compromised in Cell-Fit-HD as compared to the FNTD alone. Neither cell coating and culturing, nor additional staining procedures affected the properties of the FNTD surface to detect ion tracks. Standard immunofluorescence and live staining procedures could be employed to co-register cell biology and ion track information. The Cell-Fit-Hybrid Detector system is a promising platform for a multitude of studies linking biological response to energy deposition at high level of optical microscopy resolution.

Quantitative Characterization of Cell Behaviors through Cell Cycle Progression via Automated Cell Tracking

PubMed Central

Wang, Yuliang; Jeong, Younkoo; Jhiang, Sissy M.; Yu, Lianbo; Menq, Chia-Hsiang

2014-01-01

Cell behaviors are reflections of intracellular tension dynamics and play important roles in many cellular processes. In this study, temporal variations in cell geometry and cell motion through cell cycle progression were quantitatively characterized via automated cell tracking for MCF-10A non-transformed breast cells, MCF-7 non-invasive breast cancer cells, and MDA-MB-231 highly metastatic breast cancer cells. A new cell segmentation method, which combines the threshold method and our modified edge based active contour method, was applied to optimize cell boundary detection for all cells in the field-of-view. An automated cell-tracking program was implemented to conduct live cell tracking over 40 hours for the three cell lines. The cell boundary and location information was measured and aligned with cell cycle progression with constructed cell lineage trees. Cell behaviors were studied in terms of cell geometry and cell motion. For cell geometry, cell area and cell axis ratio were investigated. For cell motion, instantaneous migration speed, cell motion type, as well as cell motion range were analyzed. We applied a cell-based approach that allows us to examine and compare temporal variations of cell behavior along with cell cycle progression at a single cell level. Cell body geometry along with distribution of peripheral protrusion structures appears to be associated with cell motion features. Migration speed together with motion type and motion ranges are required to distinguish the three cell-lines examined. We found that cells dividing or overlapping vertically are unique features of cell malignancy for both MCF-7 and MDA-MB-231 cells, whereas abrupt changes in cell body geometry and cell motion during mitosis are unique to highly metastatic MDA-MB-231 cells. Taken together, our live cell tracking system serves as an invaluable tool to identify cell behaviors that are unique to malignant and/or highly metastatic breast cancer cells. PMID:24911281

Uncertainty Footprint: Visualization of Nonuniform Behavior of Iterative Algorithms Applied to 4D Cell Tracking

PubMed Central

Wan, Y.; Hansen, C.

2018-01-01

Research on microscopy data from developing biological samples usually requires tracking individual cells over time. When cells are three-dimensionally and densely packed in a time-dependent scan of volumes, tracking results can become unreliable and uncertain. Not only are cell segmentation results often inaccurate to start with, but it also lacks a simple method to evaluate the tracking outcome. Previous cell tracking methods have been validated against benchmark data from real scans or artificial data, whose ground truth results are established by manual work or simulation. However, the wide variety of real-world data makes an exhaustive validation impossible. Established cell tracking tools often fail on new data, whose issues are also difficult to diagnose with only manual examinations. Therefore, data-independent tracking evaluation methods are desired for an explosion of microscopy data with increasing scale and resolution. In this paper, we propose the uncertainty footprint, an uncertainty quantification and visualization technique that examines nonuniformity at local convergence for an iterative evaluation process on a spatial domain supported by partially overlapping bases. We demonstrate that the patterns revealed by the uncertainty footprint indicate data processing quality in two algorithms from a typical cell tracking workflow – cell identification and association. A detailed analysis of the patterns further allows us to diagnose issues and design methods for improvements. A 4D cell tracking workflow equipped with the uncertainty footprint is capable of self diagnosis and correction for a higher accuracy than previous methods whose evaluation is limited by manual examinations. PMID:29456279

Towards magnetic-enhanced cellular uptake, MRI and chemotherapeutics delivery by magnetic mesoporous silica nanoparticles.

PubMed

Liu, Qian; Zhang, Jixi; Xia, Weiliang; Gu, Hongchen

2012-10-01

A type of nanoparticle with three functional modalities was prepared with the aim of providing a multifunctional drug delivery system. The nanoparticle was 50 nm in size, with 2.7 nm mesopores and a magnetic nanocrystal core, which was further doped with FITC to enable the tracking of cellular uptake. We demonstrated that the internalization of the nanoparticles in tumor cells could be enhanced by applying an external magnetic field and furthermore, this kind of nanoparticle could be used in magnetic targeted drug delivery. With high transverse relaxivity, the magnetic nanoparticles shortened proton relaxation time and induced high magnetic resonance imaging contrast in tumor cells. Studies on anticancer drug loading and delivery capacity of anticancer drugs also showed that this type of nanoparticles could load water-soluble doxorubicin, and produce a prominent inhibitive effect against tumor cells. Taken together, the presented nanoparticles could become a promising agent in cancer theranostics.

Emerging MRI Methods in Translational Cardiovascular Research

PubMed Central

Vandsburger, Moriel H; Epstein, Frederick H

2011-01-01

Cardiac magnetic resonance imaging (CMR) has become a reference standard modality for imaging of left ventricular (LV) structure and function, and, using late gadolinium enhancement, for imaging myocardial infarction. Emerging CMR techniques enable a more comprehensive examination of the heart, making CMR an excellent tool for use in translational cardiovascular research. Specifically, emerging CMR methods have been developed to measure the extent of myocardial edema, changes in ventricular mechanics, changes in tissue composition as a result of fibrosis, and changes in myocardial perfusion as a function of both disease and infarct healing. New CMR techniques also enable the tracking of labeled cells, molecular imaging of biomarkers of disease, and changes in calcium flux in cardiomyocytes. In addition, MRI can quantify blood flow velocity and wall shear stress in large blood vessels. Almost all of these techniques can be applied in both pre-clinical and clinical settings, enabling both the techniques themselves and the knowledge gained using such techniques in pre-clinical research to be translated from the lab bench to the patient bedside. PMID:21452060

Seeing Stem Cells at Work In Vivo

PubMed Central

Srivastava, Amit K.; Bulte, Jeff W. M.

2013-01-01

Stem cell based-therapies are novel therapeutic strategies that hold key for developing new treatments for diseases conditions with very few or no cures. Although there has been an increase in the number of clinical trials involving stem cell-based therapies in the last few years, the long-term risks and benefits of these therapies are still unknown. Detailed in vivo studies are needed to monitor the fate of transplanted cells, including their distribution, differentiation, and longevity over time. Advancements in non-invasive cellular imaging techniques to track engrafted cells in real-time present a powerful tool for determining the efficacy of stem cell-based therapies. In this review, we describe the latest approaches to stem cell labeling and tracking using different imaging modalities. PMID:23975604

Innovative molecular-based fluorescent nanoparticles for multicolor single particle tracking in cells

NASA Astrophysics Data System (ADS)

Daniel, Jonathan; Godin, Antoine G.; Palayret, Matthieu; Lounis, Brahim; Cognet, Laurent; Blanchard-Desce, Mireille

2016-03-01

Based on an original molecular-based design, we present bright and photostable fluorescent organic nanoparticles (FONs) showing excellent colloidal stability in various aqueous environments. Complementary near-infrared emitting and green emitting FONs were prepared using a simple, fast and robust protocol. Both types of FONs could be simultaneously imaged at the single-particle level in solution as well as in biological environments using a monochromatic excitation and a dual-color fluorescence microscope. No evidence of acute cytotoxicity was found upon incubation of live cells with mixed solutions of FONs, and both types of nanoparticles were found internalized in the cells where their motion could be simultaneously tracked at video-rate up to minutes. These fluorescent organic nanoparticles open a novel non-toxic alternative to existing nanoparticles for imaging biological structures, compatible with live-cell experiments and specially fitted for multicolor single particle tracking.

A theranostic nanoplatform: magneto-gold@fluorescence polymer nanoparticles for tumor targeting T1&T2-MRI/CT/NIR fluorescence imaging and induction of genuine autophagy mediated chemotherapy.

PubMed

Wang, Guannan; Qian, Kun; Mei, Xifan

2018-06-14

Multifunctional nanoparticles, bearing low toxicity and tumor-targeting properties, coupled with multifunctional diagnostic imaging and enhanced treatment efficacy, have drawn tremendous attention due to their enormous potential for medical applications. Herein, we report a new kind of biocompatible and tumor-targeting magneto-gold@fluorescent polymer nanoparticle (MGFs-LyP-1), which is based on ultra-small magneto-gold (Fe 3 O 4 -Au) nanoparticles and NIR emissive fluorescent polymers by a solvent-mediated method. This kind of nanoparticle could be taken up efficiently and simultaneously serve for in vivo tumor targeting T 1 &T 2 -MRI/CT/near infrared (NIR) fluorescence bioimaging. Furthermore, the nanoparticles exhibit small size, higher tumor targeting accumulation, excellent cytocompatibility for long-term tracking, and no disturbing cell proliferation and differentiation. Moreover, clear and convincing evidence proves that as-synthesized MGFs-LyP-1 could elicit genuine autophagy via inducing autophagosome formation, which offers a definite synergistic effect to enhance cancer therapy with doxorubicin (DOX) at a nontoxic concentration through enhancement of the autophagy flux. Meanwhile, the as-prepared nanoparticles could be rapidly cleared from mice without any obvious organ impairment. The results indeed reveal a promising prospect of an MGFs-LyP-1 contrast agent with low toxicity and high efficiency for promising application in biomedicine.

Track-weighted functional connectivity (TW-FC): a tool for characterizing the structural-functional connections in the brain.

PubMed

Calamante, Fernando; Masterton, Richard A J; Tournier, Jacques-Donald; Smith, Robert E; Willats, Lisa; Raffelt, David; Connelly, Alan

2013-04-15

MRI provides a powerful tool for studying the functional and structural connections in the brain non-invasively. The technique of functional connectivity (FC) exploits the intrinsic temporal correlations of slow spontaneous signal fluctuations to characterise brain functional networks. In addition, diffusion MRI fibre-tracking can be used to study the white matter structural connections. In recent years, there has been considerable interest in combining these two techniques to provide an overall structural-functional description of the brain. In this work we applied the recently proposed super-resolution track-weighted imaging (TWI) methodology to demonstrate how whole-brain fibre-tracking data can be combined with FC data to generate a track-weighted (TW) FC map of FC networks. The method was applied to data from 8 healthy volunteers, and illustrated with (i) FC networks obtained using a seeded connectivity-based analysis (seeding in the precuneus/posterior cingulate cortex, PCC, known to be part of the default mode network), and (ii) with FC networks generated using independent component analysis (in particular, the default mode, attention, visual, and sensory-motor networks). TW-FC maps showed high intensity in white matter structures connecting the nodes of the FC networks. For example, the cingulum bundles show the strongest TW-FC values in the PCC seeded-based analysis, due to their major role in the connection between medial frontal cortex and precuneus/posterior cingulate cortex; similarly the superior longitudinal fasciculus was well represented in the attention network, the optic radiations in the visual network, and the corticospinal tract and corpus callosum in the sensory-motor network. The TW-FC maps highlight the white matter connections associated with a given FC network, and their intensity in a given voxel reflects the functional connectivity of the part of the nodes of the network linked by the structural connections traversing that voxel. They therefore contain a different (and novel) image contrast from that of the images used to generate them. The results shown in this study illustrate the potential of the TW-FC approach for the fusion of structural and functional data into a single quantitative image. This technique could therefore have important applications in neuroscience and neurology, such as for voxel-based comparison studies. Copyright © 2012 Elsevier Inc. All rights reserved.

The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity.

PubMed

Cui, Li-li; Kerkelä, Erja; Bakreen, Abdulhameed; Nitzsche, Franziska; Andrzejewska, Anna; Nowakowski, Adam; Janowski, Miroslaw; Walczak, Piotr; Boltze, Johannes; Lukomska, Barbara; Jolkkonen, Jukka

2015-01-27

Intra-arterial cell infusion is an efficient delivery route with which to target organs such as the ischemic brain. However, adverse events including microembolisms and decreased cerebral blood flow were recently reported after intra-arterial cell delivery in rodent models, raising safety concerns. We tested the hypothesis that cell dose, infusion volume, and velocity would be related to the severity of complications after intra-arterial cell delivery. In this study, 38 rats were subjected to a sham middle cerebral artery occlusion (sham-MCAO) procedure before being infused with allogeneic bone-marrow mesenchymal stem cells at different cell doses (0 to 1.0 × 10(6)), infusion volumes (0.5 to 1.0 ml), and infusion times (3 to 6 minutes). An additional group (n = 4) was infused with 1.0 × 10(6) cells labeled with iron oxide for in vivo tracking of cells. Cells were infused through the external carotid artery under laser Doppler flowmetry monitoring 48 hours after sham-MCAO. Magnetic resonance imaging (MRI) was performed 24 hours after cell infusion to reveal cerebral embolisms or hemorrhage. Limb placing, cylinder, and open field tests were conducted to assess sensorimotor functions before the rats were perfused for histology. A cell dose-related reduction in cerebral blood flow was noted, as well as an increase in embolic events and concomitant lesion size, and sensorimotor impairment. In addition, a low infusion velocity (0.5 ml/6 minutes) was associated with high rate of complications. Lesions on MRI were confirmed with histology and corresponded to necrotic cell loss and blood-brain barrier leakage. Particularly cell dose but also infusion velocity contribute to complications encountered after intra-arterial cell transplantation. This should be considered before planning efficacy studies in rats and, potentially, in patients with stroke.

Using T2-Exchange from Ln3+DOTA-Based Chelates for Contrast-Enhanced Molecular Imaging of Prostate Cancer with MRI

DTIC Science & Technology

2015-04-01

antigen ( PSMA ) of prostate cancer cells would then be synthesized and tested with both in vitro and in vivo experiments. Major Findings: We found that the...simplified chemistry. 15. SUBJECT TERMS MRI Contrast Agent, T2 contrast, Prostate Cancer, PSMA Targeted Agent, Early Detection and Diagnosis, Dysprosium... PSMA ), which is significantly over-expressed by prostate cancer cells, has proven to be an excellent target for imaging prostate cancer in mouse

Motion compensation for MRI-compatible patient-mounted needle guide device: estimation of targeting accuracy in MRI-guided kidney cryoablations

NASA Astrophysics Data System (ADS)

Tokuda, Junichi; Chauvin, Laurent; Ninni, Brian; Kato, Takahisa; King, Franklin; Tuncali, Kemal; Hata, Nobuhiko

2018-04-01

Patient-mounted needle guide devices for percutaneous ablation are vulnerable to patient motion. The objective of this study is to develop and evaluate a software system for an MRI-compatible patient-mounted needle guide device that can adaptively compensate for displacement of the device due to patient motion using a novel image-based automatic device-to-image registration technique. We have developed a software system for an MRI-compatible patient-mounted needle guide device for percutaneous ablation. It features fully-automated image-based device-to-image registration to track the device position, and a device controller to adjust the needle trajectory to compensate for the displacement of the device. We performed: (a) a phantom study using a clinical MR scanner to evaluate registration performance; (b) simulations using intraoperative time-series MR data acquired in 20 clinical cases of MRI-guided renal cryoablations to assess its impact on motion compensation; and (c) a pilot clinical study in three patients to test its feasibility during the clinical procedure. FRE, TRE, and success rate of device-to-image registration were mm, mm, and 98.3% for the phantom images. The simulation study showed that the motion compensation reduced the targeting error for needle placement from 8.2 mm to 5.4 mm (p  <  0.0005) in patients under general anesthesia (GA), and from 14.4 mm to 10.0 mm () in patients under monitored anesthesia care (MAC). The pilot study showed that the software registered the device successfully in a clinical setting. Our simulation study demonstrated that the software system could significantly improve targeting accuracy in patients treated under both MAC and GA. Intraprocedural image-based device-to-image registration was feasible.

Tracking targeted bimodal nanovaccines: immune responses and routing in cells, tissue, and whole organism.

PubMed

Cruz, Luis J; Tacken, Paul J; Zeelenberg, Ingrid S; Srinivas, Mangala; Bonetto, Fernando; Weigelin, Bettina; Eich, Christina; de Vries, I Jolanda; Figdor, Carl G

2014-12-01

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs), involved in the induction of immunity and currently exploited for antitumor immunotherapies. An optimized noninvasive imaging modality capable of determining and quantifying DC-targeted nanoparticle (NP) trajectories could provide valuable information regarding therapeutic vaccine outcome. Here, targeted poly(d,l-lactide-co-glycolide) nanoparticles (PLGA NPs) recognizing DC receptors were equipped with superparamagnetic iron oxide particles (SPIO) or gold nanoparticles with fluorescently labeled antigen. The fluorescent label allowed for rapid analysis and quantification of DC-specific uptake of targeted PLGA NPs in comparison to uptake by other cells. Transmission electron microscopy (TEM) showed that a fraction of the encapsulated antigen reached the lysosomal compartment of DCs, where SPIO and gold were already partially released. However, part of the PLGA NPs localized within the cytoplasm, as confirmed by confocal microscopy. DCs targeted with NPs carrying SPIO or fluorescent antigen were detected within lymph nodes as early as 1 h after injection by magnetic resonance imaging (MRI). Despite the fact that targeting did not markedly affect PLGA NP biodistribution on organism and tissue level, it increased delivery of NPs to DCs residing in peripheral lymph nodes and resulted in enhanced T cell proliferation. In conclusion, two imaging agents within a single carrier allows tracking of targeted PLGA NPs at the subcellular, cellular, and organismal levels, thereby facilitating the rational design of in vivo targeted vaccination strategies.

Accelerating Dynamic Magnetic Resonance Imaging (MRI) for Lung Tumor Tracking Based on Low-Rank Decomposition in the Spatial–Temporal Domain: A Feasibility Study Based on Simulation and Preliminary Prospective Undersampled MRI

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

Sarma, Manoj; Department of Radiation Oncology, University of California, Los Angeles, California; Hu, Peng

Purpose: To evaluate a low-rank decomposition method to reconstruct down-sampled k-space data for the purpose of tumor tracking. Methods and Materials: Seven retrospective lung cancer patients were included in the simulation study. The fully-sampled k-space data were first generated from existing 2-dimensional dynamic MR images and then down-sampled by 5 × -20 × before reconstruction using a Cartesian undersampling mask. Two methods, a low-rank decomposition method using combined dynamic MR images (k-t SLR based on sparsity and low-rank penalties) and a total variation (TV) method using individual dynamic MR frames, were used to reconstruct images. The tumor trajectories were derived on the basis ofmore » autosegmentation of the resultant images. To further test its feasibility, k-t SLR was used to reconstruct prospective data of a healthy subject. An undersampled balanced steady-state free precession sequence with the same undersampling mask was used to acquire the imaging data. Results: In the simulation study, higher imaging fidelity and low noise levels were achieved with the k-t SLR compared with TV. At 10 × undersampling, the k-t SLR method resulted in an average normalized mean square error <0.05, as opposed to 0.23 by using the TV reconstruction on individual frames. Less than 6% showed tracking errors >1 mm with 10 × down-sampling using k-t SLR, as opposed to 17% using TV. In the prospective study, k-t SLR substantially reduced reconstruction artifacts and retained anatomic details. Conclusions: Magnetic resonance reconstruction using k-t SLR on highly undersampled dynamic MR imaging data results in high image quality useful for tumor tracking. The k-t SLR was superior to TV by better exploiting the intrinsic anatomic coherence of the same patient. The feasibility of k-t SLR was demonstrated by prospective imaging acquisition and reconstruction.« less

Classifying MCI Subtypes in Community-Dwelling Elderly Using Cross-Sectional and Longitudinal MRI-Based Biomarkers

PubMed Central

Guan, Hao; Liu, Tao; Jiang, Jiyang; Tao, Dacheng; Zhang, Jicong; Niu, Haijun; Zhu, Wanlin; Wang, Yilong; Cheng, Jian; Kochan, Nicole A.; Brodaty, Henry; Sachdev, Perminder; Wen, Wei

2017-01-01

Amnestic MCI (aMCI) and non-amnestic MCI (naMCI) are considered to differ in etiology and outcome. Accurately classifying MCI into meaningful subtypes would enable early intervention with targeted treatment. In this study, we employed structural magnetic resonance imaging (MRI) for MCI subtype classification. This was carried out in a sample of 184 community-dwelling individuals (aged 73–85 years). Cortical surface based measurements were computed from longitudinal and cross-sectional scans. By introducing a feature selection algorithm, we identified a set of discriminative features, and further investigated the temporal patterns of these features. A voting classifier was trained and evaluated via 10 iterations of cross-validation. The best classification accuracies achieved were: 77% (naMCI vs. aMCI), 81% (aMCI vs. cognitively normal (CN)) and 70% (naMCI vs. CN). The best results for differentiating aMCI from naMCI were achieved with baseline features. Hippocampus, amygdala and frontal pole were found to be most discriminative for classifying MCI subtypes. Additionally, we observed the dynamics of classification of several MRI biomarkers. Learning the dynamics of atrophy may aid in the development of better biomarkers, as it may track the progression of cognitive impairment. PMID:29085292

Application of unscented Kalman filter for robust pose estimation in image-guided surgery

NASA Astrophysics Data System (ADS)

Vaccarella, Alberto; De Momi, Elena; Valenti, Marta; Ferrigno, Giancarlo; Enquobahrie, Andinet

2012-02-01

Image-guided surgery (IGS) allows clinicians to view current, intra-operative scenes superimposed on preoperative images (typically MRI or CT scans). IGS systems use localization systems to track and visualize surgical tools overlaid on top of preoperative images of the patient during surgery. The most commonly used localization systems in the Operating Rooms (OR) are optical tracking systems (OTS) due to their ease of use and cost effectiveness. However, OTS' suffer from the major drawback of line-of-sight requirements. State space approaches based on different implementations of the Kalman filter have recently been investigated in order to compensate for short line-of-sight occlusion. However, the proposed parameterizations for the rigid body orientation suffer from singularities at certain values of rotation angles. The purpose of this work is to develop a quaternion-based Unscented Kalman Filter (UKF) for robust optical tracking of both position and orientation of surgical tools in order to compensate marker occlusion issues. This paper presents preliminary results towards a Kalman-based Sensor Management Engine (SME). The engine will filter and fuse multimodal tracking streams of data. This work was motivated by our experience working in robot-based applications for keyhole neurosurgery (ROBOCAST project). The algorithm was evaluated using real data from NDI Polaris tracker. The results show that our estimation technique is able to compensate for marker occlusion with a maximum error of 2.5° for orientation and 2.36 mm for position. The proposed approach will be useful in over-crowded state-of-the-art ORs where achieving continuous visibility of all tracked objects will be difficult.

New robust algorithm for tracking cells in videos of Drosophila morphogenesis based on finding an ideal path in segmented spatio-temporal cellular structures.

PubMed

Bellaïche, Yohanns; Bosveld, Floris; Graner, François; Mikula, Karol; Remesíková, Mariana; Smísek, Michal

2011-01-01

In this paper, we present a novel algorithm for tracking cells in time lapse confocal microscopy movie of a Drosophila epithelial tissue during pupal morphogenesis. We consider a 2D + time video as a 3D static image, where frames are stacked atop each other, and using a spatio-temporal segmentation algorithm we obtain information about spatio-temporal 3D tubes representing evolutions of cells. The main idea for tracking is the usage of two distance functions--first one from the cells in the initial frame and second one from segmented boundaries. We track the cells backwards in time. The first distance function attracts the subsequently constructed cell trajectories to the cells in the initial frame and the second one forces them to be close to centerlines of the segmented tubular structures. This makes our tracking algorithm robust against noise and missing spatio-temporal boundaries. This approach can be generalized to a 3D + time video analysis, where spatio-temporal tubes are 4D objects.

Glucose-installed, SPIO-loaded PEG- b-PCL micelles as MR contrast agents to target prostate cancer cells

NASA Astrophysics Data System (ADS)

Theerasilp, Man; Sunintaboon, Panya; Sungkarat, Witaya; Nasongkla, Norased

2017-11-01

Polymeric micelles of poly(ethylene glycol)- block-poly(ɛ-caprolactone) bearing glucose analog encapsulated with superparamagnetic iron oxide nanoparticles (Glu-SPIO micelles) were synthesized as an MRI contrast agent to target cancer cells based on high-glucose metabolism. Compared to SPIO micelles (non-targeting SPIO micelles), Glu-SPIO micelles demonstrated higher toxicity to human prostate cancer cell lines (PC-3) at high concentration. Atomic absorption spectroscopy was used to determine the amount of iron in cells. It was found that the iron in cancer cells treated by Glu-SPIO micelles were 27-fold higher than cancer cells treated by SPIO micelles at the iron concentration of 25 ppm and fivefold at the iron concentration of 100 ppm. To implement Glu-SPIO micelles as a MR contrast agent, the 3-T clinical MRI was applied to determine transverse relaxivities ( r 2*) and relaxation rate (1/ T 2*) values. In vitro MRI showed different MRI signal from cancer cells after cellular uptake of SPIO micelles and Glu-SPIO micelles. Glu-SPIO micelles was highly sensitive with the r 2* in agarose gel at 155 mM-1 s-1. Moreover, the higher 1/ T 2* value was found for cancer cells treated with Glu-SPIO micelles. These results supported that glucose ligand increased the cellular uptake of micelles by PC-3 cells with over-expressing glucose transporter on the cell membrane. Thus, glucose can be used as a small molecule ligand for targeting prostate cancer cells overexpressing glucose transporter.

Tracking Perfluorocarbon Nanoemulsion Delivery by 19F MRI for Precise High Intensity Focused Ultrasound Tumor Ablation

PubMed Central

Shin, Soo Hyun; Park, Eun-Joo; Min, Changki; Choi, Sun Il; Jeon, Soyeon; Kim, Yun-Hee; Kim, Daehong

2017-01-01

Perfluorocarbon nanoemulsions (PFCNEs) have recently been undergoing rigorous study to investigate their ability to improve the therapeutic efficacy of tumor ablation by high intensity focused ultrasound (HIFU). For precise control of PFCNE delivery and thermal ablation, their accumulation and distribution in a tumor should be quantitatively analyzed. Here, we used fluorine-19 (19F) magnetic resonance imaging (MRI) to quantitatively track PFCNE accumulation in a tumor, and analyzed how intra-tumoral PFCNE quantities affect the therapeutic efficacy of HIFU treatment. Ablation outcomes were assessed by intra-voxel incoherent motion analysis and bioluminescent imaging up to 14 days after the procedure. Assessment of PFCNE delivery and treatment outcomes showed that 2-3 mg/mL of PFCNE in a tumor produces the largest ablation volume under the same HIFU insonation conditions. Histology showed varying degrees of necrosis depending on the amount of PFCNE delivered. 19F MRI promises to be a valuable platform for precisely guiding PFCNE-enhanced HIFU ablation of tumors. PMID:28255351

Magnetic Labeling of Activated Microglia in Experimental Gliomas1

PubMed Central

Fleige, Gerrit; Nolte, Christiane; Synowitz, Michael; Seeberger, Florian; Kettenmann, Helmut; Zimmer, Claus

2001-01-01

Abstract Microglia, as intrinsic immunoeffector cells of the central nervous system (CNS), play a very sensitive, crucial role in the response to almost any brain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether these cells can be visualized with magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of the tumor, but also allow for assessing the status of immunologic defense. Using USPIOs in cell culture experiments and in a rat glioma model, we showed that microglia can be labeled magnetically. Labeled microglia are detected by confocal microscopy within and around tumors in a typical border-like pattern. Quantitative in vitro studies revealed that microglia internalize amounts of USPIOs that are significantly higher than those incorporated by tumor cells and astrocytes. Labeled microglia can be detected and quantified with MRI in cell phantoms, and the extent of the tumor can be seen in glioma-bearing rats in vivo. We conclude that magnetic labeling of microglia provides a potential tool for MRI of gliomas, which reflects tumor morphology precisely. Furthermore, the results suggest that MRI may yield functional data on the immunologic reaction of the CNS. PMID:11774031

Real-time Magnetic Resonance Imaging Guidance for Cardiovascular Procedures

PubMed Central

Horvath, Keith A.; Li, Ming; Mazilu, Dumitru; Guttman, Michael A.; McVeigh, Elliot R.

2008-01-01

Magnetic resonance imaging (MRI) of the cardiovascular system has proven to be an invaluable diagnostic tool. Given the ability to allow for real-time imaging, MRI guidance of intraoperative procedures can provide superb visualization which can facilitate a variety of interventions and minimize the trauma of the operations as well. In addition to the anatomic detail, MRI can provide intraoperative assessment of organ and device function. Instruments and devices can be marked to enhance visualization and tracking. All of which is an advance over standard x-ray or ultrasonic imaging. PMID:18395633

Design and development of novel MRI compatible zirconium- ruthenium alloys with ultralow magnetic susceptibility.

PubMed

Li, H F; Zhou, F Y; Li, L; Zheng, Y F

2016-04-19

In the present study, novel MRI compatible zirconium-ruthenium alloys with ultralow magnetic susceptibility were developed for biomedical and therapeutic devices under MRI diagnostics environments. The results demonstrated that alloying with ruthenium into pure zirconium would significantly increase the strength and hardness properties. The corrosion resistance of zirconium-ruthenium alloys increased significantly. High cell viability could be found and healthy cell morphology observed when culturing MG 63 osteoblast-like cells and L-929 fibroblast cells with zirconium-ruthenium alloys, whereas the hemolysis rates of zirconium-ruthenium alloys are <1%, much lower than 5%, the safe value for biomaterials according to ISO 10993-4 standard. Compared with conventional biomedical 316L stainless steel, Co-Cr alloys and Ti-based alloys, the magnetic susceptibilities of the zirconium-ruthenium alloys (1.25 × 10(-6) cm(3)·g(-1)-1.29 × 10(-6) cm(3)·g(-1) for zirconium-ruthenium alloys) are ultralow, about one-third that of Ti-based alloys (Ti-6Al-4V, ~3.5 × 10(-6) cm(3)·g(-1), CP Ti and Ti-6Al-7Nb, ~3.0 × 10(-6) cm(3)·g(-1)), and one-sixth that of Co-Cr alloys (Co-Cr-Mo, ~7.7 × 10(-6) cm(3)·g(-1)). Among the Zr-Ru alloy series, Zr-1Ru demonstrates enhanced mechanical properties, excellent corrosion resistance and cell viability with lowest magnetic susceptibility, and thus is the optimal Zr-Ru alloy system as therapeutic devices under MRI diagnostics environments.

Dipy, a library for the analysis of diffusion MRI data.

PubMed

Garyfallidis, Eleftherios; Brett, Matthew; Amirbekian, Bagrat; Rokem, Ariel; van der Walt, Stefan; Descoteaux, Maxime; Nimmo-Smith, Ian

2014-01-01

Diffusion Imaging in Python (Dipy) is a free and open source software project for the analysis of data from diffusion magnetic resonance imaging (dMRI) experiments. dMRI is an application of MRI that can be used to measure structural features of brain white matter. Many methods have been developed to use dMRI data to model the local configuration of white matter nerve fiber bundles and infer the trajectory of bundles connecting different parts of the brain. Dipy gathers implementations of many different methods in dMRI, including: diffusion signal pre-processing; reconstruction of diffusion distributions in individual voxels; fiber tractography and fiber track post-processing, analysis and visualization. Dipy aims to provide transparent implementations for all the different steps of dMRI analysis with a uniform programming interface. We have implemented classical signal reconstruction techniques, such as the diffusion tensor model and deterministic fiber tractography. In addition, cutting edge novel reconstruction techniques are implemented, such as constrained spherical deconvolution and diffusion spectrum imaging (DSI) with deconvolution, as well as methods for probabilistic tracking and original methods for tractography clustering. Many additional utility functions are provided to calculate various statistics, informative visualizations, as well as file-handling routines to assist in the development and use of novel techniques. In contrast to many other scientific software projects, Dipy is not being developed by a single research group. Rather, it is an open project that encourages contributions from any scientist/developer through GitHub and open discussions on the project mailing list. Consequently, Dipy today has an international team of contributors, spanning seven different academic institutions in five countries and three continents, which is still growing.

Dipy, a library for the analysis of diffusion MRI data

PubMed Central

Garyfallidis, Eleftherios; Brett, Matthew; Amirbekian, Bagrat; Rokem, Ariel; van der Walt, Stefan; Descoteaux, Maxime; Nimmo-Smith, Ian

2014-01-01

Diffusion Imaging in Python (Dipy) is a free and open source software project for the analysis of data from diffusion magnetic resonance imaging (dMRI) experiments. dMRI is an application of MRI that can be used to measure structural features of brain white matter. Many methods have been developed to use dMRI data to model the local configuration of white matter nerve fiber bundles and infer the trajectory of bundles connecting different parts of the brain. Dipy gathers implementations of many different methods in dMRI, including: diffusion signal pre-processing; reconstruction of diffusion distributions in individual voxels; fiber tractography and fiber track post-processing, analysis and visualization. Dipy aims to provide transparent implementations for all the different steps of dMRI analysis with a uniform programming interface. We have implemented classical signal reconstruction techniques, such as the diffusion tensor model and deterministic fiber tractography. In addition, cutting edge novel reconstruction techniques are implemented, such as constrained spherical deconvolution and diffusion spectrum imaging (DSI) with deconvolution, as well as methods for probabilistic tracking and original methods for tractography clustering. Many additional utility functions are provided to calculate various statistics, informative visualizations, as well as file-handling routines to assist in the development and use of novel techniques. In contrast to many other scientific software projects, Dipy is not being developed by a single research group. Rather, it is an open project that encourages contributions from any scientist/developer through GitHub and open discussions on the project mailing list. Consequently, Dipy today has an international team of contributors, spanning seven different academic institutions in five countries and three continents, which is still growing. PMID:24600385

Design and development of an ethnically-diverse imaging informatics-based eFolder system for multiple sclerosis patients.

PubMed

Ma, Kevin C; Fernandez, James R; Amezcua, Lilyana; Lerner, Alex; Shiroishi, Mark S; Liu, Brent J

2015-12-01

MRI has been used to identify multiple sclerosis (MS) lesions in brain and spinal cord visually. Integrating patient information into an electronic patient record system has become key for modern patient care in medicine in recent years. Clinically, it is also necessary to track patients' progress in longitudinal studies, in order to provide comprehensive understanding of disease progression and response to treatment. As the amount of required data increases, there exists a need for an efficient systematic solution to store and analyze MS patient data, disease profiles, and disease tracking for both clinical and research purposes. An imaging informatics based system, called MS eFolder, has been developed as an integrated patient record system for data storage and analysis of MS patients. The eFolder system, with a DICOM-based database, includes a module for lesion contouring by radiologists, a MS lesion quantification tool to quantify MS lesion volume in 3D, brain parenchyma fraction analysis, and provide quantitative analysis and tracking of volume changes in longitudinal studies. Patient data, including MR images, have been collected retrospectively at University of Southern California Medical Center (USC) and Los Angeles County Hospital (LAC). The MS eFolder utilizes web-based components, such as browser-based graphical user interface (GUI) and web-based database. The eFolder database stores patient clinical data (demographics, MS disease history, family history, etc.), MR imaging-related data found in DICOM headers, and lesion quantification results. Lesion quantification results are derived from radiologists' contours on brain MRI studies and quantified into 3-dimensional volumes and locations. Quantified results of white matter lesions are integrated into a structured report based on DICOM-SR protocol and templates. The user interface displays patient clinical information, original MR images, and viewing structured reports of quantified results. The GUI also includes a data mining tool to handle unique search queries for MS. System workflow and dataflow steps has been designed based on the IHE post-processing workflow profile, including workflow process tracking, MS lesion contouring and quantification of MR images at a post-processing workstation, and storage of quantitative results as DICOM-SR in DICOM-based storage system. The web-based GUI is designed to display zero-footprint DICOM web-accessible data objects (WADO) and the SR objects. The MS eFolder system has been designed and developed as an integrated data storage and mining solution in both clinical and research environments, while providing unique features, such as quantitative lesion analysis and disease tracking over a longitudinal study. A comprehensive image and clinical data integrated database provided by MS eFolder provides a platform for treatment assessment, outcomes analysis and decision-support. The proposed system serves as a platform for future quantitative analysis derived automatically from CAD algorithms that can also be integrated within the system for individual disease tracking and future MS-related research. Ultimately the eFolder provides a decision-support infrastructure that can eventually be used as add-on value to the overall electronic medical record. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design and development of an ethnically-diverse imaging informatics-based eFolder system for multiple sclerosis patients

PubMed Central

Ma, Kevin C.; Fernandez, James R.; Amezcua, Lilyana; Lerner, Alex; Shiroishi, Mark S.; Liu, Brent J.

2016-01-01

Purpose MRI has been used to identify multiple sclerosis (MS) lesions in brain and spinal cord visually. Integrating patient information into an electronic patient record system has become key for modern patient care in medicine in recent years. Clinically, it is also necessary to track patients' progress in longitudinal studies, in order to provide comprehensive understanding of disease progression and response to treatment. As the amount of required data increases, there exists a need for an efficient systematic solution to store and analyze MS patient data, disease profiles, and disease tracking for both clinical and research purposes. Method An imaging informatics based system, called MS eFolder, has been developed as an integrated patient record system for data storage and analysis of MS patients. The eFolder system, with a DICOM-based database, includes a module for lesion contouring by radiologists, a MS lesion quantification tool to quantify MS lesion volume in 3D, brain parenchyma fraction analysis, and provide quantitative analysis and tracking of volume changes in longitudinal studies. Patient data, including MR images, have been collected retrospectively at University of Southern California Medical Center (USC) and Los Angeles County Hospital (LAC). The MS eFolder utilizes web-based components, such as browser-based graphical user interface (GUI) and web-based database. The eFolder database stores patient clinical data (demographics, MS disease history, family history, etc.), MR imaging-related data found in DICOM headers, and lesion quantification results. Lesion quantification results are derived from radiologists' contours on brain MRI studies and quantified into 3-dimensional volumes and locations. Quantified results of white matter lesions are integrated into a structured report based on DICOM-SR protocol and templates. The user interface displays patient clinical information, original MR images, and viewing structured reports of quantified results. The GUI also includes a data mining tool to handle unique search queries for MS. System workflow and dataflow steps has been designed based on the IHE post-processing workflow profile, including workflow process tracking, MS lesion contouring and quantification of MR images at a post-processing workstation, and storage of quantitative results as DICOM-SR in DICOM-based storage system. The web-based GUI is designed to display zero-footprint DICOM web-accessible data objects (WADO) and the SR objects. Summary The MS eFolder system has been designed and developed as an integrated data storage and mining solution in both clinical and research environments, while providing unique features, such as quantitative lesion analysis and disease tracking over a longitudinal study. A comprehensive image and clinical data integrated database provided by MS eFolder provides a platform for treatment assessment, outcomes analysis and decision-support. The proposed system serves as a platform for future quantitative analysis derived automatically from CAD algorithms that can also be integrated within the system for individual disease tracking and future MS-related research. Ultimately the eFolder provides a decision-support infrastructure that can eventually be used as add-on value to the overall electronic medical record. PMID:26564667

MO-FG-BRA-07: Theranostic Gadolinium-Based AGuIX Nanoparticles for MRI-Guided Radiation Therapy

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

Detappe, A; Institut Lumiere-Matiere, Villeurbanne; Nano-H, St-Quentin Fallavier

2015-06-15

Purpose: AGuIX are gadolinium-based nanoparticles, initially developed for MRI, that have a potential role in radiation therapy as a radiosensitizer. Our goal is to demonstrate that these nanoparticles can both be used as an MRI contrast agent, as well as to obtain local dose enhancement in a pancreatic tumor when delivered in combination with an external beam irradiation. Methods: We performed in vitro cell uptake and radiosensitization studies of a pancreatic cancer cell line in a low energy (220kVp) beam, a standard clinical 6MV beam (STD) and a flattening filter free clinical 6MV beam (FFF). After injection of 40mM ofmore » nanoparticles, a biodistribution study was performed in vivo on mice with subcutaneous xenograft pancreatic tumors. In vivo radiation therapy studies were performed at the time point of maximum tumor uptake. Results: The concentration of AGuIX nanoparticles in Panc-1 pancreatic cancer cells, determined in vitro by MRI and ICPMS, peaks after 30 minutes with 0.3% of the initial concentration (5mg/g). Clonogenic assays show a significant effect (p<0.05) when the AGuIX are coupled with MV photon irradiation (DEF20%=1.31). Similar AGuIX tumor uptake is found in vivo by both MRI and ICPMS 30 minutes after intravenous injection. For long term survival studies, the choice of the radiation dose is determined with 5 control groups (3mice/group) irradiated with 0, 5, 10, 15, and 20Gy. Afterwards, 4 groups (8mice/group) are used to evaluate the effect of the nanoparticles. A Logrank test is performed as a statistical test to evaluate the effect of the nanoparticles. Conclusion: The combination of the MRI contrast and radiosensitization properties of gadolinium nanoparticles reveals a strong potential for usage with MRI-guided radiation therapy.« less

Paramagnetic fluorinated nanoemulsions for sensitive cellular fluorine-19 magnetic resonance imaging

PubMed Central

Kislukhin, Alexander A.; Xu, Hongyan; Adams, Stephen R.; Narsinh, Kazim H.; Tsien, Roger Y.; Ahrens, Eric T.

2016-01-01

Fluorine-19 magnetic resonance imaging (19F MRI) probes enable quantitative in vivo detection of cell therapies and inflammatory cells. Here, we describe the formulation of perfluorocarbon-based nanoemulsions with improved sensitivity for cellular MRI. Reduction of the 19F spin-lattice relaxation time (T1) enables rapid imaging and an improved signal-to-noise ratio, thereby improving cell detection sensitivity. We synthesized metal-binding β-diketones conjugated to linear perfluoropolyether (PFPE), formulated these fluorinated ligands as aqueous nanoemulsions, and then metalated them with various transition and lanthanide ions in the fluorous phase. Iron(III) tris-β-diketonate ('FETRIS') nanoemulsions with PFPE have low cytotoxicity (<20%) and superior MRI properties. Moreover, the 19F T1 can readily be reduced by an order of magnitude and tuned by stoichiometric modulation of the iron concentration. The resulting 19F MRI detection sensitivity is enhanced by 3-to-5 fold over previously used tracers at 11.7 T, and is predicted to increase by at least 8-fold at clinical field strength of 3 T. PMID:26974409

Studying microstructure and microstructural changes in plant tissues by advanced diffusion magnetic resonance imaging techniques

PubMed Central

Morozov, Darya; Tal, Iris; Pisanty, Odelia; Shani, Eilon

2017-01-01

Abstract As sessile organisms, plants must respond to the environment by adjusting their growth and development. Most of the plant body is formed post-embryonically by continuous activity of apical and lateral meristems. The development of lateral adventitious roots is a complex process, and therefore the development of methods that can visualize, non-invasively, the plant microstructure and organ initiation that occur during growth and development is of paramount importance. In this study, relaxation-based and advanced diffusion magnetic resonance imaging (MRI) methods including diffusion tensor (DTI), q-space diffusion imaging (QSI), and double-pulsed-field-gradient (d-PFG) MRI, at 14.1 T, were used to characterize the hypocotyl microstructure and the microstructural changes that occurred during the development of lateral adventitious roots in tomato. Better contrast was observed in relaxation-based MRI using higher in-plane resolution but this also resulted in a significant reduction in the signal-to-noise ratio of the T2-weighted MR images. Diffusion MRI revealed that water diffusion is highly anisotropic in the vascular cylinder. QSI and d-PGSE MRI showed that in the vascular cylinder some of the cells have sizes in the range of 6–10 μm. The MR images captured cell reorganization during adventitious root formation in the periphery of the primary vascular bundles, adjacent to the xylem pole that broke through the cortex and epidermis layers. This study demonstrates that MRI and diffusion MRI methods allow the non-invasive study of microstructural features of plants, and enable microstructural changes associated with adventitious root formation to be followed. PMID:28398563

Optical/MRI Multimodality Molecular Imaging

NASA Astrophysics Data System (ADS)

Ma, Lixin; Smith, Charles; Yu, Ping

2007-03-01

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

Brain activation of semantic category-based grouping in multiple identity tracking task

PubMed Central

Wei, Liuqing; Lyu, Chuang; Hu, Siyuan; Li, Zhen

2017-01-01

Using Multiple Identity Tracking task and the functional magnetic resonance imaging (fMRI) technology, the present study aimed to isolate and visualize the functional anatomy of neural systems involved in the semantic category-based grouping process. Three experiment conditions were selected and compared: the category-based targets grouping (TG) condition, the targets-distractors grouping (TDG) condition and the homogenous condition. In the TG condition, observers could utilize the categorical distinction between targets and distractors, to construct a uniform presentation of targets, that is, to form a group of the targets to facilitate tracking. In the TDG condition, half the targets and half the distractors belonged to the same category. Observers had to inhibit the grouping of targets and distractors in one category to complete tracking. In the homogenous condition, where targets and distractors consisted of the same objects, no grouping could be formed. The “TG-Homogenous” contrast (p<0.01) revealed the activation of the left fusiform and the pars triangularis of inferior frontal gyrus (IFG). The “TG-TDG” contrast only revealed the activation of the left anterior cingulate gyrus (ACC). The fusiform and IFG pars triangularis might participate in the representation of semantic knowledge, IFG pars triangularis might relate intensely with the classification of semantic categories. The ACC might be responsible for the initiation and maintenance of grouping representation. PMID:28505166

Live-cell MRI with xenon hyper-CEST biosensors targeted to metabolically labeled cell-surface glycans.

PubMed

Witte, Christopher; Martos, Vera; Rose, Honor May; Reinke, Stefan; Klippel, Stefan; Schröder, Leif; Hackenberger, Christian P R

2015-02-23

The targeting of metabolically labeled glycans with conventional MRI contrast agents has proved elusive. In this work, which further expands the utility of xenon Hyper-CEST biosensors in cell experiments, we present the first successful molecular imaging of such glycans using MRI. Xenon Hyper-CEST biosensors are a novel class of MRI contrast agents with very high sensitivity. We designed a multimodal biosensor for both fluorescent and xenon MRI detection that is targeted to metabolically labeled sialic acid through bioorthogonal chemistry. Through the use of a state of the art live-cell bioreactor, it was demonstrated that xenon MRI biosensors can be used to image cell-surface glycans at nanomolar concentrations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Engineering cell-fluorescent ion track hybrid detectors

PubMed Central

2013-01-01

Background The lack of sensitive biocompatible particle track detectors has so far limited parallel detection of physical energy deposition and biological response. Fluorescent nuclear track detectors (FNTDs) based on Al2O3:C,Mg single crystals combined with confocal laser scanning microscopy (CLSM) provide 3D information on ion tracks with a resolution limited by light diffraction. Here we report the development of next generation cell-fluorescent ion track hybrid detectors (Cell-Fit-HD). Methods The biocompatibility of FNTDs was tested using six different cell lines, i.e. human non-small cell lung carcinoma (A549), glioblastoma (U87), androgen independent prostate cancer (PC3), epidermoid cancer (A431) and murine (VmDk) glioma SMA-560. To evaluate cell adherence, viability and conformal coverage of the crystals different seeding densities and alternative coating with extracellular matrix (fibronectin) was tested. Carbon irradiation was performed in Bragg peak (initial 270.55 MeV u−1). A series of cell compartment specific fluorescence stains including nuclear (HOECHST), membrane (Glut-1), cytoplasm (Calcein AM, CM-DiI) were tested on Cell-Fit-HDs and a single CLSM was employed to co-detect the physical (crystal) as well as the biological (cell layer) information. Results The FNTD provides a biocompatible surface. Among the cells tested, A549 cells formed the most uniform, viable, tightly packed epithelial like monolayer. The ion track information was not compromised in Cell-Fit-HD as compared to the FNTD alone. Neither cell coating and culturing, nor additional staining procedures affected the properties of the FNTD surface to detect ion tracks. Standard immunofluorescence and live staining procedures could be employed to co-register cell biology and ion track information. Conclusions The Cell-Fit-Hybrid Detector system is a promising platform for a multitude of studies linking biological response to energy deposition at high level of optical microscopy resolution. PMID:23758749

Real-Time Tracking of Motor Response Activation and Response Competition in a Stroop Task in Young Children: A Lateralized Readiness Potential Study

ERIC Educational Resources Information Center

Szucs, Denes; Soltesz, Fruzsina; Bryce, Donna; Whitebread, David

2009-01-01

The ability to select an appropriate motor response by resolving competition among alternative responses plays a major role in cognitive performance. fMRI studies suggest that the development of this skill is related to the maturation of the frontal cortex that underlies the improvement of motor inhibition abilities. However, fMRI cannot…

Developing 3D microscopy with CLARITY on human brain tissue: Towards a tool for informing and validating MRI-based histology.

PubMed

Morawski, Markus; Kirilina, Evgeniya; Scherf, Nico; Jäger, Carsten; Reimann, Katja; Trampel, Robert; Gavriilidis, Filippos; Geyer, Stefan; Biedermann, Bernd; Arendt, Thomas; Weiskopf, Nikolaus

2017-11-28

Recent breakthroughs in magnetic resonance imaging (MRI) enabled quantitative relaxometry and diffusion-weighted imaging with sub-millimeter resolution. Combined with biophysical models of MR contrast the emerging methods promise in vivo mapping of cyto- and myelo-architectonics, i.e., in vivo histology using MRI (hMRI) in humans. The hMRI methods require histological reference data for model building and validation. This is currently provided by MRI on post mortem human brain tissue in combination with classical histology on sections. However, this well established approach is limited to qualitative 2D information, while a systematic validation of hMRI requires quantitative 3D information on macroscopic voxels. We present a promising histological method based on optical 3D imaging combined with a tissue clearing method, Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging compatible Tissue hYdrogel (CLARITY), adapted for hMRI validation. Adapting CLARITY to the needs of hMRI is challenging due to poor antibody penetration into large sample volumes and high opacity of aged post mortem human brain tissue. In a pilot experiment we achieved transparency of up to 8 mm-thick and immunohistochemical staining of up to 5 mm-thick post mortem brain tissue by a combination of active and passive clearing, prolonged clearing and staining times. We combined 3D optical imaging of the cleared samples with tailored image processing methods. We demonstrated the feasibility for quantification of neuron density, fiber orientation distribution and cell type classification within a volume with size similar to a typical MRI voxel. The presented combination of MRI, 3D optical microscopy and image processing is a promising tool for validation of MRI-based microstructure estimates. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

SU-G-JeP1-15: Sliding Window Prior Data Assisted Compressed Sensing for MRI Lung Tumor Tracking

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

Yip, E; Wachowicz, K; Rathee, S

Purpose: Prior Data Assisted Compressed Sensing (PDACS) is a partial k-space acquisition and reconstruction method for mobile tumour (i.e. lung) tracking using on-line MRI in radiotherapy. PDACS partially relies on prior data acquired at the beginning of dynamic scans, and is therefore susceptible to artifacts in longer duration scan due to slow drifts in MR signal. A novel sliding window strategy is presented to mitigate this effect. Methods: MRI acceleration is simulated by retrospective removal of data from the fully sampled sets. Six lung cancer patients were scanned (clinical 3T MRI) using a balanced steady state free precession (bSSFP) sequencemore » for 3 minutes at approximately 4 frames per second, for a total of 650 dynamics. PDACS acceleration is achieved by undersampling of k-space in a single pseudo-random pattern. Reconstruction iteratively minimizes the total variations while constraining the images to satisfy both the currently acquired data and the prior data in missing k-space. Our novel sliding window technique (SW-PDACS), uses a series of distinct pseudo-random under-sampling patterns of partial k-space – with the prior data drawn from a sliding window of the most recent data available. Under-sampled data, simulating 2 – 5x acceleration are reconstructed using PDACS and SW-PDACS. Three quantitative metrics: artifact power, centroid error and Dice’s coefficient are computed for comparison. Results: Quantitively metric values from all 6 patients are averaged in 3 bins, each containing approximately one minute of dynamic data. For the first minute bin, PDACS and SW-PDACS give comparable results. Progressive decline in image quality metrics in bins 2 and 3 are observed for PDACS. No decline in image quality is observed for SW-PDACS. Conclusion: The novel approach presented (SW-PDACS) is a more robust for accelerating longer duration (>1 minute) dynamic MRI scans for tracking lung tumour motion using on-line MRI in radiotherapy. B.G. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).« less

Tractography of Association Fibers Associated with Language Processing.

PubMed

Egger, K; Yang, S; Reisert, M; Kaller, C; Mader, I; Beume, L; Weiller, C; Urbach, H

2015-10-01

Several major association fiber tracts are known to be part of the language processing system. There is evidence that high angular diffusion-based MRI is able to separate these fascicles in a constant way. In this study, we wanted to proof this thesis using a novel whole brain "global tracking" approach and to test for possible lateralization. Global tracking was performed in six healthy right-handed volunteers for the arcuate fascicle (AF), the medial longitudinal fascicle (MdLF), the inferior fronto-occipital fascicle (IFOF), and the inferior longitudinal fascicle (ILF). These fiber tracts were characterized quantitatively using the number of streamlines (SL) and the mean fractional anisotropy (FA). We were able to characterize the AF, the MdLF, the IFOF, and the ILF consistently in six healthy volunteers using global tracking. A left-sided dominance (LI > 0.2) for the AF was found in all participants. The MdLF showed a left-sided dominance in four participants (one female, three male). Regarding the FA, no lateralization (LI > 0.2) could be shown in any of the fascicles. Using a novel global tracking algorithm we confirmed that the courses of the primary language processing associated fascicles can consistently be differentiated. Additionally we were able to show a streamline-based left-sided lateralization in the AF of all right-handed healthy subjects.

Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study.

PubMed

Kim, Y S; Choi, Y J; Lee, S W; Kwon, O R; Suh, D S; Heo, D B; Koh, Y G

2016-02-01

Cartilage regenerative procedures using the cell-based tissue engineering approach involving mesenchymal stem cells (MSCs) have been receiving increased interest because of their potential for altering the progression of osteoarthritis (OA) by repairing cartilage lesions. The aim of this study was to investigate the clinical and magnetic resonance imaging (MRI) outcomes of MSC implantation in OA knees and to determine the association between clinical and MRI outcomes. Twenty patients (24 knees) who underwent arthroscopic MSC implantation for cartilage lesions in their OA knees were evaluated at 2 years after surgery. Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed according to the MRI Osteoarthritis Knee Score (MOAKS) and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. The clinical outcomes significantly improved (P < 0.001 for both). The cartilage lesion grades (as described in MOAKS [grades for size of cartilage-loss area and percentage of full-thickness cartilage loss]) at follow-up MRI were significantly better than the preoperative values (P < 0.001 for both). The clinical outcomes at final follow-up were significantly correlated with the MOAKS and MOCART score at follow-up MRI (P < 0.05 for all). Considering the encouraging clinical and MRI outcomes obtained and the significant correlations noted between the clinical and MRI outcomes, MSC implantation seems to be useful for repairing cartilage lesions in OA knees. However, a larger sample size and long-term studies are needed to confirm our findings. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A role for bioelectric effects in the induction of bystander signals by ionizing radiation?

PubMed

Mothersill, C; Moran, G; McNeill, F; Gow, M D; Denbeigh, J; Prestwich, W; Seymour, C B

2007-04-03

The induction of "bystander effects" i.e. effects in cells which have not received an ionizing radiation track, is now accepted but the mechanisms are not completely clear. Bystander effects following high and low LET radiation exposure are accepted but mechanisms are still not understood. There is some evidence for a physical component to the signal. This paper tests the hypothesis that bioelectric or biomagnetic phenomena are involved. Human immortalized skin keratinocytes and primary explants of mouse bladder and fish skin, were exposed directly to ionizing radiation or treated in a variety of bystander protocols. Exposure of cells was conducted by shielding one group of flasks using lead, to reduce the dose below the threshold of 2mGy (60)Cobalt gamma rays established for the bystander effect. The endpoint for the bystander effect in the reporter system used was reduction in cloning efficiency (RCE). The magnitude of the RCE was similar in shielded and unshielded flasks. When cells were placed in a Faraday cage the magnitude of the RCE was less but not eliminated. The results suggest that liquid media or cell-cell contact transmission of bystander factors may be only part of the bystander mechanism. Bioelectric or bio magnetic fields may have a role to play. To test this further, cells were placed in a Magnetic Resonance Imaging (MRI) machine for 10 min using a typical head scan protocol. This treatment also induced a bystander response. Apart from the obvious clinical relevance, the MRI results further suggest that bystander effects may be produced by non-ionizing exposures. It is concluded that bioelectric or magnetic effects may be involved in producing bystander signaling cascades commonly seen following ionizing radiation exposure.

A Role for Bioelectric Effects in the Induction of Bystander Signals by Ionizing Radiation?

PubMed Central

Mothersill, C.; Moran, G.; McNeill, F.; Gow, M.D.; Denbeigh, J.; Prestwich, W.; Seymour, C.B.

2007-01-01

The induction of “bystander effects” i.e. effects in cells which have not received an ionizing radiation track, is now accepted but the mechanisms are not completely clear. Bystander effects following high and low LET radiation exposure are accepted but mechanisms are still not understood. There is some evidence for a physical component to the signal. This paper tests the hypothesis that bioelectric or biomagnetic phenomena are involved. Human immortalized skin keratinocytes and primary explants of mouse bladder and fish skin, were exposed directly to ionizing radiation or treated in a variety of bystander protocols. Exposure of cells was conducted by shielding one group of flasks using lead, to reduce the dose below the threshold of 2mGy 60Cobalt gamma rays established for the bystander effect. The endpoint for the bystander effect in the reporter system used was reduction in cloning efficiency (RCE). The magnitude of the RCE was similar in shielded and unshielded flasks. When cells were placed in a Faraday cage the magnitude of the RCE was less but not eliminated. The results suggest that liquid media or cell-cell contact transmission of bystander factors may be only part of the bystander mechanism. Bioelectric or bio magnetic fields may have a role to play. To test this further, cells were placed in a Magnetic Resonance Imaging (MRI) machine for 10min using a typical head scan protocol. This treatment also induced a bystander response. Apart from the obvious clinical relevance, the MRI results further suggest that bystander effects may be produced by non-ionizing exposures. It is concluded that bioelectric or magnetic effects may be involved in producing bystander signaling cascades commonly seen following ionizing radiation exposure. PMID:18648606

Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters

PubMed Central

Wang, Hai-yi; Su, Zi-hua; Xu, Xiao; Sun, Zhi-peng; Duan, Fei-xue; Song, Yuan-yuan; Li, Lu; Wang, Ying-wei; Ma, Xin; Guo, Ai-tao; Ma, Lin; Ye, Hui-yi

2016-01-01

Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan–rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K trans & Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters. PMID:27380733

Design of biomimetic vascular grafts with magnetic endothelial patterning.

PubMed

Fayol, Delphine; Le Visage, Catherine; Ino, Julia; Gazeau, Florence; Letourneur, Didier; Wilhelm, Claire

2013-01-01

The development of small diameter vascular grafts with a controlled pluricellular organization is still needed for effective vascular tissue engineering. Here, we describe a technological approach combining a tubular scaffold and magnetically labeled cells to create a pluricellular and organized vascular graft, the endothelialization of which could be monitored by MRI prior to transplantation. A novel type of scaffold was developed with a tubular geometry and a porous bulk structure enabling the seeding of cells in the scaffold pores. A homogeneous distribution of human mesenchymal stem cells in the macroporous structure was obtained by seeding the freeze-dried scaffold with the cell suspension. The efficient covering of the luminal surface of the tube was then made possible thanks to the implementation of a magnetic-based patterning technique. Human endothelial cells or endothelial progenitors were magnetically labeled with iron oxide nanoparticles and successfully attracted to the 2-mm lumen where they attached and formed a continuous endothelium. The combination of imaging modalities [fluorescence imaging, histology, and 3D magnetic resonance imaging (MRI)] evidenced the integrity of the vascular construct. In particular, the observation of different cell organizations in a vascular scaffold within the range of resolution of single cells by 4.7 T MRI is reported.

Design of quantum dot-conjugated lipids for long-term, high-speed tracking experiments on cell surfaces.

PubMed

Murcia, Michael J; Minner, Daniel E; Mustata, Gina-Mirela; Ritchie, Kenneth; Naumann, Christoph A

2008-11-12

The current study reports the facile design of quantum dot (QD)-conjugated lipids and their application to high-speed tracking experiments on cell surfaces. CdSe/ZnS core/shell QDs with two types of hydrophilic coatings, 2-(2-aminoethoxy)ethanol (AEE) and a 60:40 molar mixture of 1,2-dipalmitoyl- sn-glycero-3-phosphocholine and 1,2-dipalmitoyl- sn-glycero-3-phosphoethanolamine- N-[methoxy(polyethylene glycol-2000], are conjugated to sulfhydryl lipids via maleimide reactive groups on the QD surface. Prior to lipid conjugation, the colloidal stability of both types of coated QDs in aqueous solution is confirmed using fluorescence correlation spectroscopy. A sensitive assay based on single lipid tracking experiments on a planar solid-supported phospholipid bilayer is presented that establishes conditions of monovalent conjugation of QDs to lipids. The QD-lipids are then employed as single-molecule tracking probes in plasma membranes of several cell types. Initial tracking experiments at a frame rate of 30 frames/s corroborate that QD-lipids diffuse like dye-labeled lipids in the plasma membrane of COS-7, HEK-293, 3T3, and NRK cells, thus confirming monovalent labeling. Finally, QD-lipids are applied for the first time to high-speed single-molecule imaging by tracking their lateral mobility in the plasma membrane of NRK fibroblasts with up to 1000 frames/s. Our high-speed tracking data, which are in excellent agreement with previous tracking experiments that used larger (40 nm) Au labels, not only push the time resolution in long-time, continuous fluorescence-based single-molecule tracking but also show that highly photostable, photoluminescent nanoprobes of 10 nm size can be employed (AEE-coated QDs). These probes are also attractive because, unlike Au nanoparticles, they facilitate complex multicolor experiments.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

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

A Retrospective Cohort Study of Lesion Distribution of HIV-1 Infection Patients With Cryptococcal Meningoencephalitis on MRI: Correlation With Immunity and Immune Reconstitution.

PubMed

Xia, Shuang; Li, Xueqin; Shi, Yanbin; Liu, Jinxin; Zhang, Mengjie; Gu, Tenghui; Pan, Shinong; Song, Liucun; Xu, Jinsheng; Sun, Yan; Zhao, Qingxia; Lu, Zhiyan; Lu, Puxuan; Li, Hongjun

2016-02-01

The objective of this paper is to correlate the MRI distribution of cryptococcal meningoencephalitis in HIV-1 infection patients with CD4 T cell count and immune reconstitution effect.A large retrospective cohort study of HIV patients from multi-HIV centers in China was studied to demonstrate the MRI distribution of cryptococcal meningoencephalitis and its correlation with the different immune status.The consecutive clinical and neuroimaging data of 55 HIV-1-infected patients with cryptococcal meningoencephalitis collected at multi-HIV centers in China during the years of 2011 to 2014 was retrospectively analyzed. The enrolled patients were divided into 2 groups based on the distribution of lesions. One group of patients had their lesions at the central brain (group 1, n = 34) and the other group of patients had their lesions at the superficial brain (group 2, n = 21). We explored their MRI characterization of brain. In addition, we also compared their CD4 T cell counts and immune reconstitution effects between the 2 groups based on the imaging findings.No statistical difference was found in terms of age and gender between the 2 groups. The medians of CD4 T cell counts were 11.67 cells/mm (3.00-52.00 cells/mm) in group 1 and 42.00 cells/mm (10.00-252.00 cells/mm) in group 2. Statistical difference of CD4 T cell count was found between the 2 groups (P = 0.023). Thirteen patients in group 1 (13/34) and 12 patients in group 2 (12/21) received highly active antiretroviral treatment (HAART). Patients of group 2 received HAART therapy more frequently than patients of group 1 (P = 0.021).Central and superficial brain lesions detected by MR imaging in HIV-1-infected patients with cryptococcal meningoencephalitis are in correlation with the host immunity and HAART therapy.

Eye-Tracking Provides a Sensitive Measure of Exploration Deficits After Acute Right MCA Stroke

PubMed Central

Delazer, Margarete; Sojer, Martin; Ellmerer, Philipp; Boehme, Christian; Benke, Thomas

2018-01-01

The eye-tracking study aimed at assessing spatial biases in visual exploration in patients after acute right MCA (middle cerebral artery) stroke. Patients affected by unilateral neglect show less functional recovery and experience severe difficulties in everyday life. Thus, accurate diagnosis is essential, and specific treatment is required. Early assessment is of high importance as rehabilitative interventions are more effective when applied soon after stroke. Previous research has shown that deficits may be overlooked when classical paper-and-pencil tasks are used for diagnosis. Conversely, eye-tracking allows direct monitoring of visual exploration patterns. We hypothesized that the analysis of eye-tracking provides more sensitive measures for spatial exploration deficits after right middle cerebral artery stroke. Twenty-two patients with right MCA stroke (median 5 days after stroke) and 28 healthy controls were included. Lesions were confirmed by MRI/CCT. Groups performed comparably in the Mini–Mental State Examination (patients and controls median 29) and in a screening of executive functions. Eleven patients scored at ceiling in neglect screening tasks, 11 showed minimal to severe signs of unilateral visual neglect. An overlap plot based on MRI and CCT imaging showed lesions in the temporo–parieto–frontal cortex, basal ganglia, and adjacent white matter tracts. Visual exploration was evaluated in two eye-tracking tasks, one assessing free visual exploration of photographs, the other visual search using symbols and letters. An index of fixation asymmetries proved to be a sensitive measure of spatial exploration deficits. Both patient groups showed a marked exploration bias to the right when looking at complex photographs. A single case analysis confirmed that also most of those patients who showed no neglect in screening tasks performed outside the range of controls in free exploration. The analysis of patients’ scoring at ceiling in neglect screening tasks is of special interest, as possible deficits may be overlooked and thus remain untreated. Our findings are in line with other studies suggesting considerable limitations of laboratory screening procedures to fully appreciate the occurrence of neglect symptoms. Future investigations are needed to explore the predictive value of the eye-tracking index and its validity in everyday situations.

Tracking and nowcasting convective precipitation cells at European scale for transregional warnings

NASA Astrophysics Data System (ADS)

Meyer, Vera; Tüchler, Lukas

2013-04-01

A transregional overview of the current weather situation is considered as highly valuable information to assist forecasters as well as official authorities for disaster management in their decision making processes. The development of the European-wide radar composite OPERA enables for the first time a coherent object-oriented tracking and nowcasting of intense precipitation cells in real time at continental scale and at a resolution of 2 x 2 km² and 15 minutes. Recently, the object-oriented cell-tracking tool A-TNT (Austrian Thunderstorm Nowcasting Tool) has been developed at ZAMG. A-TNT utilizes the method of ec-TRAM [1]. It consists of two autonomously operating routines, which identify, track and nowcast radar- and lightning-cells separately. The two independent outputs are combined to a coherent storm monitoring and nowcasting in a final step. Within the framework of HAREN (Hazard Assessment based on Rainfall European Nowcasts), which is a project funded by the EC Directorate General for Humanitarian Aid and Civil Protection, A-TNT has been adapted to OPERA radar data. The objective of HAREN is the support of forecasters and official authorities in their decision-making processes concerning precipitation induced hazards with pan-European information. This study will present (1) the general performance of the object-oriented approach for thunderstorm tracking and nowcasting on continental scale giving insight into its current capabilities and limitations and (2) the utilization of object-oriented cell information for automated precipitation warnings carried out within the framework of HAREN. Data collected from April to October 2012 are used to assess the performance of cell-tracking based on radar data. Furthermore, the benefit of additional lightning information provided by the European Cooperation for Lightning Detection (EUCLID) for thunderstorm tracking and nowcasting will be summarized in selected analyses. REFERENCES: [1] Meyer, V. K., H. Höller, and H. D. Betz 2012: Automated thunderstorm tracking and nowcasting: utilization of three-dimensional lightning and radar data. Manuscript accepted for publication in ACPD.

[Interest of tricuspid annular displacement (TAD) in evaluation of right ventricular ejection fraction].

PubMed

Hugues, T; Ducreux, D; Bertora, D; Berthier, F; Lemoigne, F; Padovani, B; Gibelin, P

2010-04-01

The ultrasound assessment of RV structure and function is often sub-optimal. The range of excursions of the mitral or tricuspid annulus measured in millimetre by 2D or TM-mode in centimetre per second by DTI-mode echocardiography has been shown to reflect the systolic function of both ventricles. We studied a new technique based on a tissue tracking algorithm that is ultrasound beam angle independent for automated detection of tricuspid annular displacement (TAD) (QLAB, Philips Medical Imaging). Twenty-six patients (pts) referred for magnetic resonance imaging (MRI) and 44 control subjects underwent a complete transthoracic echocardiography. MRI of the right ventricular ejection fraction (RVEF) was correlated by linear regression with TAD. Sixteen pts (61.5%) exhibited right ventricular systolic dysfunction (MRI RVEF<40%). The MRI RVEF was positively correlated with TAD (R(2)=0,65; p<0,0001). A value of TAD <14mm predicted right ventricular dysfunction with a sensitivity of 87.5% and a specificity of 90%. Most of (90%) healthy subjects exhibited TAD values exceeding this cut-off point (mean: 16.9+/-1.64mm; range: 13.3 to 24.8mm). Negative correlation was found between TAD and age (R(2)=0,36; p<0,0001). Our study is the first to correlate TAD with MRI RVEF. TAD is a simple, rapid, and non-invasive tool for right ventricular systolic function assessment.

Mathematical imaging methods for mitosis analysis in live-cell phase contrast microscopy.

PubMed

Grah, Joana Sarah; Harrington, Jennifer Alison; Koh, Siang Boon; Pike, Jeremy Andrew; Schreiner, Alexander; Burger, Martin; Schönlieb, Carola-Bibiane; Reichelt, Stefanie

2017-02-15

In this paper we propose a workflow to detect and track mitotic cells in time-lapse microscopy image sequences. In order to avoid the requirement for cell lines expressing fluorescent markers and the associated phototoxicity, phase contrast microscopy is often preferred over fluorescence microscopy in live-cell imaging. However, common specific image characteristics complicate image processing and impede use of standard methods. Nevertheless, automated analysis is desirable due to manual analysis being subjective, biased and extremely time-consuming for large data sets. Here, we present the following workflow based on mathematical imaging methods. In the first step, mitosis detection is performed by means of the circular Hough transform. The obtained circular contour subsequently serves as an initialisation for the tracking algorithm based on variational methods. It is sub-divided into two parts: in order to determine the beginning of the whole mitosis cycle, a backwards tracking procedure is performed. After that, the cell is tracked forwards in time until the end of mitosis. As a result, the average of mitosis duration and ratios of different cell fates (cell death, no division, division into two or more daughter cells) can be measured and statistics on cell morphologies can be obtained. All of the tools are featured in the user-friendly MATLAB®Graphical User Interface MitosisAnalyser. Copyright © 2017. Published by Elsevier Inc.

Wall shear stress estimation in the aorta: Impact of wall motion, spatiotemporal resolution, and phase noise.

PubMed

Zimmermann, Judith; Demedts, Daniel; Mirzaee, Hanieh; Ewert, Peter; Stern, Heiko; Meierhofer, Christian; Menze, Bjoern; Hennemuth, Anja

2018-04-01

Wall shear stress (WSS) presents an important parameter for assessing blood flow characteristics and evaluating flow-mediated lesions in the aorta. To investigate the robustness of WSS and oscillatory shear index (OSI) estimation based on 4D flow MRI against vessel wall motion, spatiotemporal resolution, and velocity encoding (VENC). Simulated and prospective. Synthetic 4D flow MRI data of the aorta, simulated using the Lattice-Boltzmann method; in vivo 4D flow MRI data of the aorta from healthy volunteers (n = 11) and patients with congenital heart defects (n = 17). 1.5T; 4D flow MRI with PEAK-GRAPPA acceleration and prospective electrocardiogram triggering. Predicated upon 3D cubic B-splines interpolation of the image velocity field, WSS was estimated in mid-systole, early-diastole, and late-diastole and OSI was derived. We assessed the impact of spatiotemporal resolution and phase noise, and compared results based on tracked-using deformable registration-and static vessel wall location. Bland-Altman analysis to assess WSS/OSI differences; Hausdorff distance (HD) to assess wall motion; and Pearson's correlation coefficient (PCC) to assess correlation of HD with WSS. Synthetic data results show systematic over-/underestimation of WSS when different spatial resolution (mean ± 1.96 SD up to -0.24 ± 0.40 N/m 2 and 0.5 ± 1.38 N/m 2 for 8-fold and 27-fold voxel size, respectively) and VENC-depending phase noise (mean ± 1.96 SD up to 0.31 ± 0.12 N/m 2 and 0.94 ± 0.28 N/m 2 for 2-fold and 4-fold VENC increase, respectively) are given. Neglecting wall motion when defining the vessel wall perturbs WSS estimates to a considerable extent (1.96 SD up to 1.21 N/m 2 ) without systematic over-/underestimation (Bland-Altman mean range -0.06 to 0.05). In addition to sufficient spatial resolution and velocity to noise ratio, accurate tracking of the vessel wall is essential for reliable image-based WSS estimation and should not be neglected if wall motion is present. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Image-guided Navigation of Single-element Focused Ultrasound Transducer

PubMed Central

Kim, Hyungmin; Chiu, Alan; Park, Shinsuk; Yoo, Seung-Schik

2014-01-01

The spatial specificity and controllability of focused ultrasound (FUS), in addition to its ability to modify the excitability of neural tissue, allows for the selective and reversible neuromodulation of the brain function, with great potential in neurotherapeutics. Intra-operative magnetic resonance imaging (MRI) guidance (in short, MRg) has limitations due to its complicated examination logistics, such as fixation through skull screws to mount the stereotactic frame, simultaneous sonication in the MRI environment, and restrictions in choosing MR-compatible materials. In order to overcome these limitations, an image-guidance system based on optical tracking and pre-operative imaging data is developed, separating the imaging acquisition for guidance and sonication procedure for treatment. Techniques to define the local coordinates of the focal point of sonication are presented. First, mechanical calibration detects the concentric rotational motion of a rigid-body optical tracker, attached to a straight rod mimicking the sonication path, pivoted at the virtual FUS focus. The spatial error presented in the mechanical calibration was compensated further by MRI-based calibration, which estimates the spatial offset between the navigated focal point and the ground-truth location of the sonication focus obtained from a temperature-sensitive MR sequence. MRI-based calibration offered a significant decrease in spatial errors (1.9±0.8 mm; 57% reduction) compared to the mechanical calibration method alone (4.4±0.9 mm). Using the presented method, pulse-mode FUS was applied to the motor area of the rat brain, and successfully stimulated the motor cortex. The presented techniques can be readily adapted for the transcranial application of FUS to intact human brain. PMID:25232203

Tilted pillar array fabrication by the combination of proton beam writing and soft lithography for microfluidic cell capture Part 2: Image sequence analysis based evaluation and biological application.

PubMed

Járvás, Gábor; Varga, Tamás; Szigeti, Márton; Hajba, László; Fürjes, Péter; Rajta, István; Guttman, András

2018-02-01

As a continuation of our previously published work, this paper presents a detailed evaluation of a microfabricated cell capture device utilizing a doubly tilted micropillar array. The device was fabricated using a novel hybrid technology based on the combination of proton beam writing and conventional lithography techniques. Tilted pillars offer unique flow characteristics and support enhanced fluidic interaction for improved immunoaffinity based cell capture. The performance of the microdevice was evaluated by an image sequence analysis based in-house developed single-cell tracking system. Individual cell tracking allowed in-depth analysis of the cell-chip surface interaction mechanism from hydrodynamic point of view. Simulation results were validated by using the hybrid device and the optimized surface functionalization procedure. Finally, the cell capture capability of this new generation microdevice was demonstrated by efficiently arresting cells from a HT29 cell-line suspension. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Uterus segmentation in dynamic MRI using LBP texture descriptors

NASA Astrophysics Data System (ADS)

Namias, R.; Bellemare, M.-E.; Rahim, M.; Pirró, N.

2014-03-01

Pelvic floor disorders cover pathologies of which physiopathology is not well understood. However cases get prevalent with an ageing population. Within the context of a project aiming at modelization of the dynamics of pelvic organs, we have developed an efficient segmentation process. It aims at alleviating the radiologist with a tedious one by one image analysis. From a first contour delineating the uterus-vagina set, the organ border is tracked along a dynamic mri sequence. The process combines movement prediction, local intensity and texture analysis and active contour geometry control. Movement prediction allows a contour intitialization for next image in the sequence. Intensity analysis provides image-based local contour detection enhanced by local binary pattern (lbp) texture descriptors. Geometry control prohibits self intersections and smoothes the contour. Results show the efficiency of the method with images produced in clinical routine.

Non-rigid estimation of cell motion in calcium time-lapse images

NASA Astrophysics Data System (ADS)

Hachi, Siham; Lucumi Moreno, Edinson; Desmet, An-Sofie; Vanden Berghe, Pieter; Fleming, Ronan M. T.

2016-03-01

Calcium imaging is a widely used technique in neuroscience permitting the simultaneous monitoring of electro- physiological activity of hundreds of neurons at single cell resolution. Identification of neuronal activity requires rapid and reliable image analysis techniques, especially when neurons fire and move simultaneously over time. Traditionally, image segmentation is performed to extract individual neurons in the first frame of a calcium sequence. Thereafter, the mean intensity is calculated from the same region of interest in each frame to infer calcium signals. However, when cells move, deform and fire, this segmentation on its own generates artefacts and therefore biased neuronal activity. Therefore, there is a pressing need to develop a more efficient cell tracking technique. We hereby present a novel vision-based cell tracking scheme using a thin-plate spline deformable model. The thin-plate spline warping is based on control points detected using the Fast from Accelerated Segment Test descriptor and tracked using the Lucas-Kanade optical flow. Our method is able to track neurons in calcium time-series, even when there are large changes in intensity, such as during a firing event. The robustness and efficiency of the proposed approach is validated on real calcium time-lapse images of a neuronal population.

Multifunctional PHPMA-Derived Polymer for Ratiometric pH Sensing, Fluorescence Imaging, and Magnetic Resonance Imaging.

PubMed

Su, Fengyu; Agarwal, Shubhangi; Pan, Tingting; Qiao, Yuan; Zhang, Liqiang; Shi, Zhengwei; Kong, Xiangxing; Day, Kevin; Chen, Meiwan; Meldrum, Deirdre; Kodibagkar, Vikram D; Tian, Yanqing

2018-01-17

In this paper, we report synthesis and characterization of a novel multimodality (MRI/fluorescence) probe for pH sensing and imaging. A multifunctional polymer was derived from poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and integrated with a naphthalimide-based-ratiometric fluorescence probe and a gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex (Gd-DOTA complex). The polymer was characterized using UV-vis absorption spectrophotometry, fluorescence spectrofluorophotometry, magnetic resonance imaging (MRI), and confocal microscopy for optical and MRI-based pH sensing and cellular imaging. In vitro labeling of macrophage J774 and esophageal CP-A cell lines shows the polymer's ability to be internalized in the cells. The transverse relaxation time (T 2 ) of the polymer was observed to be pH-dependent, whereas the spin-lattice relaxation time (T 1 ) was not. The pH probe in the polymer shows a strong fluorescence-based ratiometric pH response with emission window changes, exhibiting blue emission under acidic conditions and green emission under basic conditions, respectively. This study provides new materials with multimodalities for pH sensing and imaging.

Geometric validation of self-gating k-space-sorted 4D-MRI vs 4D-CT using a respiratory motion phantom

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

Yue, Yong, E-mail: yong.yue@cshs.org; Yang, Wensha; McKenzie, Elizabeth

Purpose: MRI is increasingly being used for radiotherapy planning, simulation, and in-treatment-room motion monitoring. To provide more detailed temporal and spatial MR data for these tasks, we have recently developed a novel self-gated (SG) MRI technique with advantage of k-space phase sorting, high isotropic spatial resolution, and high temporal resolution. The current work describes the validation of this 4D-MRI technique using a MRI- and CT-compatible respiratory motion phantom and comparison to 4D-CT. Methods: The 4D-MRI sequence is based on a spoiled gradient echo-based 3D projection reconstruction sequence with self-gating for 4D-MRI at 3 T. Respiratory phase is resolved by usingmore » SG k-space lines as the motion surrogate. 4D-MRI images are reconstructed into ten temporal bins with spatial resolution 1.56 × 1.56 × 1.56 mm{sup 3}. A MRI-CT compatible phantom was designed to validate the performance of the 4D-MRI sequence and 4D-CT imaging. A spherical target (diameter 23 mm, volume 6.37 ml) filled with high-concentration gadolinium (Gd) gel is embedded into a plastic box (35 × 40 × 63 mm{sup 3}) and stabilized with low-concentration Gd gel. The phantom, driven by an air pump, is able to produce human-type breathing patterns between 4 and 30 respiratory cycles/min. 4D-CT of the phantom has been acquired in cine mode, and reconstructed into ten phases with slice thickness 1.25 mm. The 4D images sets were imported into a treatment planning software for target contouring. The geometrical accuracy of the 4D MRI and CT images has been quantified using target volume, flattening, and eccentricity. The target motion was measured by tracking the centroids of the spheres in each individual phase. Motion ground-truth was obtained from input signals and real-time video recordings. Results: The dynamic phantom has been operated in four respiratory rate (RR) settings, 6, 10, 15, and 20/min, and was scanned with 4D-MRI and 4D-CT. 4D-CT images have target-stretching, partial-missing, and other motion artifacts in various phases, whereas the 4D-MRI images are visually free of those artifacts. Volume percentage difference for the 6.37 ml target ranged from 5.3% ± 4.3% to 10.3% ± 5.9% for 4D-CT, and 1.47 ± 0.52 to 2.12 ± 1.60 for 4D-MRI. With an increase of respiratory rate, the target volumetric and geometric deviations increase for 4D-CT images while remaining stable for the 4D-MRI images. Target motion amplitude errors at different RRs were measured with a range of 0.66–1.25 mm for 4D-CT and 0.2–0.42 mm for 4D-MRI. The results of Mann–Whitney tests indicated that 4D-MRI significantly outperforms 4D-CT in phase-based target volumetric (p = 0.027) and geometric (p < 0.001) measures. Both modalities achieve equivalent accuracy in measuring motion amplitude (p = 0.828). Conclusions: The k-space self-gated 4D-MRI technique provides a robust method for accurately imaging phase-based target motion and geometry. Compared to 4D-CT, the current 4D-MRI technique demonstrates superior spatiotemporal resolution, and robust resistance to motion artifacts caused by fast target motion and irregular breathing patterns. The technique can be used extensively in abdominal targeting, motion gating, and toward implementing MRI-based adaptive radiotherapy.« less

Design and development of novel MRI compatible zirconium- ruthenium alloys with ultralow magnetic susceptibility

PubMed Central

Li, H.F.; Zhou, F.Y.; Li, L.; Zheng, Y.F.

2016-01-01

In the present study, novel MRI compatible zirconium-ruthenium alloys with ultralow magnetic susceptibility were developed for biomedical and therapeutic devices under MRI diagnostics environments. The results demonstrated that alloying with ruthenium into pure zirconium would significantly increase the strength and hardness properties. The corrosion resistance of zirconium-ruthenium alloys increased significantly. High cell viability could be found and healthy cell morphology observed when culturing MG 63 osteoblast-like cells and L-929 fibroblast cells with zirconium-ruthenium alloys, whereas the hemolysis rates of zirconium-ruthenium alloys are <1%, much lower than 5%, the safe value for biomaterials according to ISO 10993-4 standard. Compared with conventional biomedical 316L stainless steel, Co–Cr alloys and Ti-based alloys, the magnetic susceptibilities of the zirconium-ruthenium alloys (1.25 × 10−6 cm3·g−1–1.29 × 10−6 cm3·g−1 for zirconium-ruthenium alloys) are ultralow, about one-third that of Ti-based alloys (Ti–6Al–4V, ~3.5 × 10−6 cm3·g−1, CP Ti and Ti–6Al–7Nb, ~3.0 × 10−6 cm3·g−1), and one-sixth that of Co–Cr alloys (Co–Cr–Mo, ~7.7 × 10−6 cm3·g−1). Among the Zr–Ru alloy series, Zr–1Ru demonstrates enhanced mechanical properties, excellent corrosion resistance and cell viability with lowest magnetic susceptibility, and thus is the optimal Zr–Ru alloy system as therapeutic devices under MRI diagnostics environments. PMID:27090955

Design and implementation of a MRI compatible and dynamic phantom simulating the motion of a tumor in the liver under the breathing cycle

NASA Astrophysics Data System (ADS)

Geelhand de Merxem, Arnould; Lechien, Vianney; Thibault, Tanguy; Dasnoy, Damien; Macq, Benoît

2017-11-01

In the context of cancer treatment by proton therapy, research is carried out on the use magnetic resonance imaging (MRI) to perform real-time tracking of tumors during irradiation. The purpose of this combination is to reduce the irradiation of healthy tissues surrounding the tumor, while using a non-ionizing imaging method. Therefore, it is necessary to validate the tracking algorithms on real-time MRI sequences by using physical simulators, i.e. a phantom. Our phantom is a device representing a liver with hepatocellular carcinoma, a stomach and a pancreas close to the anatomy and the magnetic properties of the human body, animated by a motion similar to the one induced by the respiration. Many anatomical or mobile phantoms already exist, but the purpose here is to combine a reliable representation of the abdominal organs with the creation and the evaluation of a programmable movement in the same device, which makes it unique. The phantom is composed of surrogate organs made of CAGN gels. These organs are placed in a transparent box filled with water and attached to an elastic membrane. A programmable electro-pneumatic system creates a movement, similarly to a human diaphragm, by inflating and deflating the membrane. The average relaxation times of the synthetic organs belongs to a range corresponding to the human organs values (T1 = [458.7-1660] ms, T2 = [39.3-89.1] ms). The displacement of the tumor is tracked in real time by a camera inside the MRI. The amplitude of the movement varies from 12.8 to 20.1 mm for a periodic and repeatable movement. Irregular breath patterns can be created with a maximum amplitude of 40 mm.

Perfusion information extracted from resting state functional magnetic resonance imaging.

PubMed

Tong, Yunjie; Lindsey, Kimberly P; Hocke, Lia M; Vitaliano, Gordana; Mintzopoulos, Dionyssios; Frederick, Blaise deB

2017-02-01

It is widely known that blood oxygenation level dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) is an indirect measure for neuronal activations through neurovascular coupling. The BOLD signal is also influenced by many non-neuronal physiological fluctuations. In previous resting state (RS) fMRI studies, we have identified a moving systemic low frequency oscillation (sLFO) in BOLD signal and were able to track its passage through the brain. We hypothesized that this seemingly intrinsic signal moves with the blood, and therefore, its dynamic patterns represent cerebral blood flow. In this study, we tested this hypothesis by performing Dynamic Susceptibility Contrast (DSC) MRI scans (i.e. bolus tracking) following the RS scans on eight healthy subjects. The dynamic patterns of sLFO derived from RS data were compared with the bolus flow visually and quantitatively. We found that the flow of sLFO derived from RS fMRI does to a large extent represent the blood flow measured with DSC. The small differences, we hypothesize, are largely due to the difference between the methods in their sensitivity to different vessel types. We conclude that the flow of sLFO in RS visualized by our time delay method represents the blood flow in the capillaries and veins in the brain.

Tracking the development of brain connectivity in adolescence through a fast Bayesian integrative method

NASA Astrophysics Data System (ADS)

Zhang, Aiying; Jia, Bochao; Wang, Yu-Ping

2018-03-01

Adolescence is a transitional period between childhood and adulthood with physical changes, as well as increasing emotional activity. Studies have shown that the emotional sensitivity is related to a second dramatical brain growth. However, there is little focus on the trend of brain development during this period. In this paper, we aim to track the functional brain connectivity development in adolescence using resting state fMRI (rs-fMRI), which amounts to a time-series analysis problem. Most existing methods either require the time point to be fairly long or are only applicable to small graphs. To this end, we adapted a fast Bayesian integrative analysis (FBIA) to address the short time-series difficulty, and combined with adaptive sum of powered score (aSPU) test for group difference. The data we used are the resting state fMRI (rs-fMRI) obtained from the publicly available Philadelphia Neurodevelopmental Cohort (PNC). They include 861 individuals aged 8-22 years who were divided into five different adolescent stages. We summarized the networks with global measurements: segregation and integration, and provided full brain functional connectivity pattern in various stages of adolescence. Moreover, our research revealed several brain functional modules development trends. Our results are shown to be both statistically and biologically significant.

Imaging features of colovesical fistulae on MRI.

PubMed

Tang, Y Z; Booth, T C; Swallow, D; Shahabuddin, K; Thomas, M; Hanbury, D; Chang, S; King, C

2012-10-01

MRI is routinely used in the investigation of colovesical fistulae at our institute. Several papers have alluded to its usefulness in achieving the diagnosis; however, there is a paucity of literature on its imaging findings. Our objective was to quantify the MRI characteristics of these fistulae. We selected all cases over a 4-year period with a final clinical diagnosis of colovesical fistula which had been investigated with MRI. The MRI scans were reviewed in a consensus fashion by two consultant uroradiologists. Their MRI features were quantified. There were 40 cases of colovesical fistulae. On MRI, the fistula morphology consistently fell into three patterns. The most common pattern (71%) demonstrated an intervening abscess between the bowel wall and bladder wall. The second pattern (15%) had a visible track between the affected bowel and bladder. The third pattern (13%) was a complete loss of fat plane between the affected bladder and bowel wall. MRI correctly determined the underlying aetiology in 63% of cases. MRI is a useful imaging modality in the diagnosis of colovesical fistulae. The fistulae appear to have three characteristic morphological patterns that may aid future diagnoses of colovesical fistulae. To the authors' knowledge, this is the first publication of the MRI findings in colovesical fistulae.

Tracking protein aggregation and mislocalization in cells with flow cytometry.

PubMed

Ramdzan, Yasmin M; Polling, Saskia; Chia, Cheryl P Z; Ng, Ivan H W; Ormsby, Angelique R; Croft, Nathan P; Purcell, Anthony W; Bogoyevitch, Marie A; Ng, Dominic C H; Gleeson, Paul A; Hatters, Danny M

2012-03-18

We applied pulse-shape analysis (PulSA) to monitor protein localization changes in mammalian cells by flow cytometry. PulSA enabled high-throughput tracking of protein aggregation, translocation from the cytoplasm to the nucleus and trafficking from the plasma membrane to the Golgi as well as stress-granule formation. Combining PulSA with tetracysteine-based oligomer sensors in a cell model of Huntington's disease enabled further separation of cells enriched with monomers, oligomers and inclusion bodies.

CNR considerations for rapid real-time MRI tumor tracking in radiotherapy hybrid devices: Effects of B{sub 0} field strength

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

Wachowicz, K., E-mail: keith.wachowicz@albertaheal

2016-08-15

Purpose: This work examines the subject of contrast-to-noise ratio (CNR), specifically between tumor and tissue background, and its dependence on the MRI field strength, B{sub 0}. This examination is motivated by the recent interest and developments in MRI/radiotherapy hybrids where real-time imaging can be used to guide treatment beams. The ability to distinguish a tumor from background tissue is of primary importance in this field, and this work seeks to elucidate the complex relationship between the CNR and B{sub 0} that is too often assumed to be purely linear. Methods: Experimentally based models of B{sub 0}-dependant relaxation for various tumormore » and normal tissues from the literature were used in conjunction with signal equations for MR sequences suitable for rapid real-time imaging to develop field-dependent predictions for CNR. These CNR models were developed for liver, lung, breast, glioma, and kidney tumors for spoiled gradient-echo, balanced steady-state free precession (bSSFP), and single-shot half-Fourier fast spin echo sequences. Results: Due to the pattern in which the relaxation properties of tissues are found to vary over B{sub 0} field (specifically the T{sub 1} time), there was always an improved CNR at lower fields compared to linear dependency. Further, in some tumor sites, the CNR at lower fields was found to be comparable to, or sometimes higher than those at higher fields (i.e., bSSFP CNR for glioma, kidney, and liver tumors). Conclusions: In terms of CNR, lower B{sub 0} fields have been shown to perform as well or better than higher fields for some tumor sites due to superior T{sub 1} contrast. In other sites this effect was less pronounced, reversing the CNR advantage. This complex relationship between CNR and B{sub 0} reveals both low and high magnetic fields as viable options for tumor tracking in MRI/radiotherapy hybrids.« less

Image fusion pitfalls for cranial radiosurgery.

PubMed

Jonker, Benjamin P

2013-01-01

Stereotactic radiosurgery requires imaging to define both the stereotactic space in which the treatment is delivered and the target itself. Image fusion is the process of using rotation and translation to bring a second image set into alignment with the first image set. This allows the potential concurrent use of multiple image sets to define the target and stereotactic space. While a single magnetic resonance imaging (MRI) sequence alone can be used for delineation of the target and fiducials, there may be significant advantages to using additional imaging sets including other MRI sequences, computed tomography (CT) scans, and advanced imaging sets such as catheter-based angiography, diffusor tension imaging-based fiber tracking and positon emission tomography in order to more accurately define the target and surrounding critical structures. Stereotactic space is usually defined by detection of fiducials on the stereotactic head frame or mask system. Unfortunately MRI sequences are susceptible to geometric distortion, whereas CT scans do not face this problem (although they have poorer resolution of the target in most cases). Thus image fusion can allow the definition of stereotactic space to proceed from the geometrically accurate CT images at the same time as using MRI to define the target. The use of image fusion is associated with risk of error introduced by inaccuracies of the fusion process, as well as workflow changes that if not properly accounted for can mislead the treating clinician. The purpose of this review is to describe the uses of image fusion in stereotactic radiosurgery as well as its potential pitfalls.

Multistability of the Brain Network for Self-other Processing

PubMed Central

Chen, Yi-An; Huang, Tsung-Ren

2017-01-01

Early fMRI studies suggested that brain areas processing self-related and other-related information were highly overlapping. Hypothesising functional localisation of the cortex, researchers have tried to locate “self-specific” and “other-specific” regions within these overlapping areas by subtracting suspected confounding signals in task-based fMRI experiments. Inspired by recent advances in whole-brain dynamic modelling, we instead explored an alternative hypothesis that similar spatial activation patterns could be associated with different processing modes in the form of different synchronisation patterns. Combining an automated synthesis of fMRI data with a presumption-free diffusion spectrum image (DSI) fibre-tracking algorithm, we isolated a network putatively composed of brain areas and white matter tracts involved in self-other processing. We sampled synchronisation patterns from the dynamical systems of this network using various combinations of physiological parameters. Our results showed that the self-other processing network, with simulated gamma-band activity, tended to stabilise at a number of distinct synchronisation patterns. This phenomenon, termed “multistability,” could serve as an alternative model in theorising the mechanism of processing self-other information. PMID:28256520

A model-based approach for automated in vitro cell tracking and chemotaxis analyses.

PubMed

Debeir, Olivier; Camby, Isabelle; Kiss, Robert; Van Ham, Philippe; Decaestecker, Christine

2004-07-01

Chemotaxis may be studied in two main ways: 1) counting cells passing through an insert (e.g., using Boyden chambers), and 2) directly observing cell cultures (e.g., using Dunn chambers), both in response to stationary concentration gradients. This article promotes the use of Dunn chambers and in vitro cell-tracking, achieved by video microscopy coupled with automatic image analysis software, in order to extract quantitative and qualitative measurements characterizing the response of cells to a diffusible chemical agent. Previously, we set up a videomicroscopy system coupled with image analysis software that was able to compute cell trajectories from in vitro cell cultures. In the present study, we are introducing a new software increasing the application field of this system to chemotaxis studies. This software is based on an adapted version of the active contour methodology, enabling each cell to be efficiently tracked for hours and resulting in detailed descriptions of individual cell trajectories. The major advantages of this method come from an improved robustness with respect to variability in cell morphologies between different cell lines and dynamical changes in cell shape during cell migration. Moreover, the software includes a very small number of parameters which do not require overly sensitive tuning. Finally, the running time of the software is very short, allowing improved possibilities in acquisition frequency and, consequently, improved descriptions of complex cell trajectories, i.e. trajectories including cell division and cell crossing. We validated this software on several artificial and real cell culture experiments in Dunn chambers also including comparisons with manual (human-controlled) analyses. We developed new software and data analysis tools for automated cell tracking which enable cell chemotaxis to be efficiently analyzed. Copyright 2004 Wiley-Liss, Inc.

SU-D-207A-05: Investigating Sparse-Sampled MRI for Motion Management in Thoracic Radiotherapy

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

Sabouri, P; Sawant, A; Arai, T

Purpose: Sparse sampling and reconstruction-based MRI techniques represent an attractive strategy to achieve sufficiently high image acquisition speed while maintaining image quality for the task of radiotherapy guidance. In this study, we examine rapid dynamic MRI using a sparse sampling sequence k-t BLAST in capturing motion-induced, cycle-to-cycle variations in tumor position. We investigate the utility of long-term MRI-based motion monitoring as a means of better characterizing respiration-induced tumor motion compared to a single-cycle 4DCT. Methods: An MRI-compatible, programmable, deformable lung motion phantom with eleven 1.5 ml water marker tubes was placed inside a 3.0 T whole-body MR scanner (Philips Ingenia).more » The phantom was programmed with 10 lung tumor motion traces previously recorded using the Synchrony system. 2D+t image sequences of a coronal slice were acquired using a balanced-SSFP sequence combined with k-t BLAST (accn=3, resolution=0.66×0.66×5 mm3; acquisition time = 110 ms/slice). kV fluoroscopic (ground truth) and 4DCT imaging was performed with the same phantom setup and motion trajectories. Marker positions in all three modalities were segmented and tracked using an opensource deformable image registration package, NiftyReg. Results: Marker trajectories obtained from rapid MRI exhibited <1 mm error compared to kv Fluoro trajectories in the presence of complex motion including baseline shifts and changes in respiratory amplitude, indicating the ability of MRI to monitor motion with adequate geometric fidelity for the purpose of radiotherapy guidance. In contrast, the trajectory derived from 4DCT exhibited significant errors up to 6 mm due to cycle-to-cycle variations and baseline shifts. Consequently, 4DCT was found to underestimate the range of marker motion by as much as 50%. Conclusion: Dynamic MRI is a promising tool for radiotherapy motion management as it permits for longterm, dose-free, soft-tissue-based monitoring of motion, yielding richer and more accurate information about tumor position and motion range compared to the current state-of-the-art, 4DCT. This work was partially supported through research funding from National Institutes of Health (R01CA169102).« less

Semiautomatic segmentation and follow-up of multicomponent low-grade tumors in longitudinal brain MRI studies

PubMed Central

Weizman, Lior; Sira, Liat Ben; Joskowicz, Leo; Rubin, Daniel L.; Yeom, Kristen W.; Constantini, Shlomi; Shofty, Ben; Bashat, Dafna Ben

2014-01-01

Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a “gold standard” was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior. PMID:24784396

The Anterior Insula Tracks Behavioral Entropy during an Interpersonal Competitive Game

PubMed Central

Matsumoto, Madoka; Matsumoto, Kenji; Omori, Takashi

2015-01-01

In competitive situations, individuals need to adjust their behavioral strategy dynamically in response to their opponent’s behavior. In the present study, we investigated the neural basis of how individuals adjust their strategy during a simple, competitive game of matching pennies. We used entropy as a behavioral index of randomness in decision-making, because maximizing randomness is thought to be an optimal strategy in the game, according to game theory. While undergoing functional magnetic resonance imaging (fMRI), subjects played matching pennies with either a human or computer opponent in each block, although in reality they played the game with the same computer algorithm under both conditions. The winning rate of each block was also manipulated. Both the opponent (human or computer), and the winning rate, independently affected subjects’ block-wise entropy during the game. The fMRI results revealed that activity in the bilateral anterior insula was positively correlated with subjects’ (not opponent’s) behavioral entropy during the game, which indicates that during an interpersonal competitive game, the anterior insula tracked how uncertain subjects’ behavior was, rather than how uncertain subjects felt their opponent's behavior was. Our results suggest that intuitive or automatic processes based on somatic markers may be a key to optimally adjusting behavioral strategies in competitive situations. PMID:26039634

Gelatin-encapsulated iron oxide nanoparticles for platinum (IV) prodrug delivery, enzyme-stimulated release and MRI.

PubMed

Cheng, Ziyong; Dai, Yunlu; Kang, Xiaojiao; Li, Chunxia; Huang, Shanshan; Lian, Hongzhou; Hou, Zhiyao; Ma, Pingan; Lin, Jun

2014-08-01

A facile method for transferring hydrophobic iron oxide nanoparticles (IONPs) from chloroform to aqueous solution via encapsulation of FITC-modified gelatin based on the hydrophobic-hydrophobic interaction is described in this report. Due to the existence of large amount of active groups such as amine groups in gelatin, the fluorescent labeling molecules of fluorescein isothiocyanate (FITC) and platinum (IV) prodrug functionalized with carboxylic groups can be conveniently conjugated on the IONPs. The nanoparticles carrying Pt(IV) prodrug exhibit good anticancer activities when the Pt(IV) complexes are reduced to Pt(II) in the intracellular environment, while the pure Pt(IV) prodrug only presents lower cytotoxicity on cancer cells. Meanwhile, fluorescence of FITC on the surface of nanoparticles was completely quenched due to the possible Förster Resonance Energy Transfer (FRET) mechanism and showed a fluorescence recovery after gelatin release and detachment from IONPs. Therefore FITC as a fluorescence probe can be used for identification, tracking and monitoring the drug release. In addition, adding pancreatic enzyme can effectively promote the gelatin release from IONPs owing to the degradation of gelatin. Noticeable darkening in magnetic resonance image (MRI) was observed at the tumor site after in situ injection of nanoparticles, indicating the IONPs-enhanced T2-weighted imaging. Our results suggest that the gelatin encapsulated Fe3O4 nanoparticles have potential applications in multi-functional drug delivery system for disease therapy, MR imaging and fluorescence sensor. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of a web-based image reporting and tracking system for assessing abdominal imaging examination quality issues in a single practice.

PubMed

Rosenkrantz, Andrew B; Johnson, Evan; Sanger, Joseph J

2015-10-01

This article presents our local experience in the implementation of a real-time web-based system for reporting and tracking quality issues relating to abdominal imaging examinations. This system allows radiologists to electronically submit examination quality issues during clinical readouts. The submitted information is e-mailed to a designate for the given modality for further follow-up; the designate may subsequently enter text describing their response or action taken, which is e-mailed back to the radiologist. Review of 558 entries over a 6-year period demonstrated documentation of a broad range of examination quality issues, including specific issues relating to protocol deviation, post-processing errors, positioning errors, artifacts, and IT concerns. The most common issues varied among US, CT, MRI, radiography, and fluoroscopy. In addition, the most common issues resulting in a patient recall for repeat imaging (generally related to protocol deviation in MRI and US) were identified. In addition to submitting quality problems, radiologists also commonly used the tool to provide recognition of a well-performed examination. An electronic log of actions taken in response to radiologists' submissions indicated that both positive and negative feedback were commonly communicated to the performing technologist. Information generated using the tool can be used to guide subsequent quality improvement initiatives within a practice, including continued protocol standardization as well as education of technologists in the optimization of abdominal imaging examinations.

Diffusion and clearance of superparamagnetic iron oxide nanoparticles infused into the rat striatum studied by MRI and histochemical techniques

NASA Astrophysics Data System (ADS)

Wang, F. H.; Kim, D. K.; Yoshitake, T.; Johansson, S. M.; Bjelke, B.; Muhammed, M.; Kehr, J.

2011-01-01

The purpose of the present study was to investigate, by MRI and histochemical techniques, the diffusion and clearance abilities of superparamagnetic iron oxide nanoparticles (SPION) coated with dextran (Dextran-SPION) and gold (Au-SPION) following their local infusions into the rat brain. In separate groups of anesthetized rats, the Dextran-SPION and Au-SPION were infused at concentrations of 0.01, 0.1, 1 and 5 µg Fe/0.5 µl and at the flow rate of 0.5 µl min - 1 into the left and right striata, respectively. Repetitive T2-weighted spin-echo MRI scans were performed at time intervals of 1, 6, 12, 24, 48, 72 h, and one, two and eight weeks after inoculation. Following infusion of Dextran-SPION (0.1 µg and 1 µg Fe), the maximal distribution volume was observed at about 12-24 h after inoculation and two weeks later the Fe signals were undetectable for the lower dose. On the other hand, Au-SPION remained tightly localized in the closest vicinity of the infusion site as revealed by unchanged MRI signal intensities and strong histochemical staining of Fe2 + and Fe3 + ions in the corresponding brain slices. Immunohistochemical staining of astrocytic and microglial reactions revealed that there were no marked differences in GFAP, VIM or OX-42 labeling observed between the nanoparticle types, however the astrocytic reaction was more pronounced in rats receiving nanoparticles compared to the control (aCSF-infused) rats. In conclusion, the present data demonstrate that the viral-sized Dextran-SPION were able to diffuse freely through the interstitial space of the brain being progressively cleared out from the infusion site within two weeks. Thus, Dextran-SPION could be beneficially used in MRI-guided diagnostic applications such as in experimental oncology or as labels and carriers for targeted drug delivery, whereas Au-SPION could be used for labeling and tracking the transplanted stem cells in experimental MRI.

Complex versus simple ankle movement training in stroke using telerehabilitation: a randomized controlled trial.

PubMed

Deng, Huiqiong; Durfee, William K; Nuckley, David J; Rheude, Brandon S; Severson, Amy E; Skluzacek, Katie M; Spindler, Kristen K; Davey, Cynthia S; Carey, James R

2012-02-01

Telerehabilitation allows rehabilitative training to continue remotely after discharge from acute care and can include complex tasks known to create rich conditions for neural change. The purposes of this study were: (1) to explore the feasibility of using telerehabilitation to improve ankle dorsiflexion during the swing phase of gait in people with stroke and (2) to compare complex versus simple movements of the ankle in promoting behavioral change and brain reorganization. This study was a pilot randomized controlled trial. Training was done in the participant's home. Testing was done in separate research labs involving functional magnetic resonance imaging (fMRI) and multi-camera gait analysis. Sixteen participants with chronic stroke and impaired ankle dorsiflexion were assigned randomly to receive 4 weeks of telerehabilitation of the paretic ankle. Participants received either computerized complex movement training (track group) or simple movement training (move group). Behavioral changes were measured with the 10-m walk test and gait analysis using a motion capture system. Brain reorganization was measured with ankle tracking during fMRI. Dorsiflexion during gait was significantly larger in the track group compared with the move group. For fMRI, although the volume, percent volume, and intensity of cortical activation failed to show significant changes, the frequency count of the number of participants showing an increase versus a decrease in these values from pretest to posttest measurements was significantly different between the 2 groups, with the track group decreasing and the move group increasing. Limitations of this study were that no follow-up test was conducted and that a small sample size was used. The results suggest that telerehabilitation, emphasizing complex task training with the paretic limb, is feasible and can be effective in promoting further dorsiflexion in people with chronic stroke.

A methodology to accurately quantify patellofemoral cartilage contact kinematics by combining 3D image shape registration and cine-PC MRI velocity data.

PubMed

Borotikar, Bhushan S; Sipprell, William H; Wible, Emily E; Sheehan, Frances T

2012-04-05

Patellofemoral osteoarthritis and its potential precursor patellofemoral pain syndrome (PFPS) are common, costly, and debilitating diseases. PFPS has been shown to be associated with altered patellofemoral joint mechanics; however, an actual variation in joint contact stresses has not been established due to challenges in accurately quantifying in vivo contact kinematics (area and location). This study developed and validated a method for tracking dynamic, in vivo cartilage contact kinematics by combining three magnetic resonance imaging (MRI) techniques, cine-phase contrast (CPC), multi-plane cine (MPC), and 3D high-resolution static imaging. CPC and MPC data were acquired from 12 healthy volunteers while they actively extended/flexed their knee within the MRI scanner. Since no gold standard exists for the quantification of in vivo dynamic cartilage contact kinematics, the accuracy of tracking a single point (patellar origin relative to the femur) represented the accuracy of tracking the kinematics of an entire surface. The accuracy was determined by the average absolute error between the PF kinematics derived through registration of MPC images to a static model and those derived through integration of the CPC velocity data. The accuracy ranged from 0.47 mm to 0.77 mm for the patella and femur and from 0.68 mm to 0.86 mm for the patellofemoral joint. For purely quantifying joint kinematics, CPC remains an analytically simpler and more accurate (accuracy <0.33 mm) technique. However, for application requiring the tracking of an entire surface, such as quantifying cartilage contact kinematics, this combined imaging approach produces accurate results with minimal operator intervention. Published by Elsevier Ltd.

"Sickle Cell Anemia: Tracking down a Mutation": An Interactive Learning Laboratory That Communicates Basic Principles of Genetics and Cellular Biology

ERIC Educational Resources Information Center

Jarrett, Kevin; Williams, Mary; Horn, Spencer; Radford, David; Wyss, J. Michael

2016-01-01

"Sickle cell anemia: tracking down a mutation" is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients…

The Role of 3T Magnetic Resonance Imaging for Targeting the Human Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease.

PubMed

Longhi, Michele; Ricciardi, Giuseppe; Tommasi, Giorgio; Nicolato, Antonio; Foroni, Roberto; Bertolasi, Laura; Beltramello, Alberto; Moretto, Giuseppe; Tinazzi, Michele; Gerosa, Massimo

2015-05-01

Chronic stimulation of the human subthalamic nucleus (STN) is gradually becoming accepted as a long-term therapeutic option for patients with advanced Parkinson disease (PD). 3Tesla (T) magnetic resonance imaging (MRI) improves contrast resolution in basal ganglia nuclei containing high levels of iron, because of magnetic susceptibility effects that increase significantly as the magnetic field gets higher. This phenomenon can be used for better visualization of the STN and may reduce the time necessary for detailed microrecording (MER) mapping, increasing surgery efficacy and lowering morbidity. The objective of this retrospective study is to analyze a population of 20 deep brain stimulation (DBS) electrode implanted patients with PD divided into two groups in which different targeting methods were used. Mean age was 56 years (range 37 to 69 years). Mean disease duration was 11.6 years. Mean follow-up was 12 months (range 6 to 36 months). Patients were divided into two groups: Group A contained 6 patients who underwent STN targeting using 1T stereotactic (T1w + T2w) MRI plus STN indirect atlas derived targeting. Group B consisted of 14 patients who underwent STN targeting using 3T nonstereotactic (T2w) MRI fused with 1T T1w stereotactic MRI and STN direct targeting. For statistical analysis, we compared (five different parameters in both (matched) groups: Unified Parkinson's disease rating scale (UPDRS) score reduction (medication off before surgery against stimulation on/medication off after surgery), postoperative drug reduction, duration of surgery, the "central preoperative track" chosen as final implantation track during surgery, and correspondence between the targeted STN and the intraoperative neurophysiologic data. Mean UPDRS III score reduction (medication off/stimulation on versus preoperative medication off) was 69% in Group A and 74% in Group B (p = 0.015, log-rank test) respectively. Postoperatively, antiparkinsonian treatment was reduced by 66% in Group A and 75% in Group B (p = 0.006, log-rank test). The preoperative "central" track (which corresponds to ideal STN targeting) proved to be the most clinically effective in 2/12 leads for Group A versus 21/28 for Group B (p < 0.001).Neurophysiologic data confirmed these results; the hypothetical target was confirmed by MER data in 76% of tracks in Group A, and in 75% of tracks in Group B (p < 0.001, univariate and multivariate analysis). 3T MRI appears to be a useful tool in STN-DBS preoperative targeting. Neurophysiologic testing remains fundamental to determine lead deepness (and prevent clinical side effects. Georg Thieme Verlag KG Stuttgart · New York.

DNA double-strand breaks and micronuclei in human blood lymphocytes after repeated whole body exposures to 7T Magnetic Resonance Imaging.

PubMed

Fatahi, Mahsa; Reddig, Annika; Vijayalaxmi; Friebe, Björn; Hartig, Roland; Prihoda, Thomas J; Ricke, Jens; Roggenbuck, Dirk; Reinhold, Dirk; Speck, Oliver

2016-06-01

To examine the extent of genetic damage, assessed from deoxyribonucleic acid (DNA) double-strand breaks (DSBs) and micronuclei (MN) in peripheral blood mononuclear cells obtained from individuals repeatedly exposed to 7T Magnetic Resonance Imaging (MRI). The study protocol was approved by the local ethics committee. Informed consent was obtained from 22 healthy, non-smoking, non-alcoholic male individuals, who had never undergone radio-/chemo-therapy, scintigraphy, and had not undergone X-ray examination one year prior blood withdrawal. Eleven participants were repeatedly exposed to 7T and 3T MRI while working with/around scanners or frequently participating as 7T and lower field MRI research subjects (mean age 34±7years). The other half was never exposed to 7T or lower field MRI and served as controls (mean age 33±9years). The damage in lymphocytes was assessed using anti-γH2AX immunofluorescence staining of DNA DSBs and by quantification of MN. Isolated cells were further exposed in vitro to 7T MRI either alone or in the presence of the DNA damaging drug etoposide, to determine if there is any additional combined effect. The kinetics of DNA damage repair were examined. The mean base-level of γH2AX foci/cell and incidence of MN between repeatedly exposed and control group were not significantly different (P=0.618 and P=0.535, respectively). The additional in vitro exposure of cells to 7T MRI had no significant impact on MN frequencies and γH2AX foci at 1, 20 and 72h after exposure. Frequently repeated 7T MRI exposure did not result in a detectable increase in genotoxicity indices and alterations of DNA repair kinetics. Copyright © 2016 Elsevier Inc. All rights reserved.

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

PubMed Central

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-01

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke. PMID:28091591

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia.

PubMed

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-16

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

NASA Astrophysics Data System (ADS)

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-01

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

CellTracker (not only) for dummies.

PubMed

Piccinini, Filippo; Kiss, Alexa; Horvath, Peter

2016-03-15

Time-lapse experiments play a key role in studying the dynamic behavior of cells. Single-cell tracking is one of the fundamental tools for such analyses. The vast majority of the recently introduced cell tracking methods are limited to fluorescently labeled cells. An equally important limitation is that most software cannot be effectively used by biologists without reasonable expertise in image processing. Here we present CellTracker, a user-friendly open-source software tool for tracking cells imaged with various imaging modalities, including fluorescent, phase contrast and differential interference contrast (DIC) techniques. CellTracker is written in MATLAB (The MathWorks, Inc., USA). It works with Windows, Macintosh and UNIX-based systems. Source code and graphical user interface (GUI) are freely available at: http://celltracker.website/ horvath.peter@brc.mta.hu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Three-dimensional histology: tools and application to quantitative assessment of cell-type distribution in rabbit heart

PubMed Central

Burton, Rebecca A.B.; Lee, Peter; Casero, Ramón; Garny, Alan; Siedlecka, Urszula; Schneider, Jürgen E.; Kohl, Peter; Grau, Vicente

2014-01-01

Aims Cardiac histo-anatomical organization is a major determinant of function. Changes in tissue structure are a relevant factor in normal and disease development, and form targets of therapeutic interventions. The purpose of this study was to test tools aimed to allow quantitative assessment of cell-type distribution from large histology and magnetic resonance imaging- (MRI) based datasets. Methods and results Rabbit heart fixation during cardioplegic arrest and MRI were followed by serial sectioning of the whole heart and light-microscopic imaging of trichrome-stained tissue. Segmentation techniques developed specifically for this project were applied to segment myocardial tissue in the MRI and histology datasets. In addition, histology slices were segmented into myocytes, connective tissue, and undefined. A bounding surface, containing the whole heart, was established for both MRI and histology. Volumes contained in the bounding surface (called ‘anatomical volume’), as well as that identified as containing any of the above tissue categories (called ‘morphological volume’), were calculated. The anatomical volume was 7.8 cm3 in MRI, and this reduced to 4.9 cm3 after histological processing, representing an ‘anatomical’ shrinkage by 37.2%. The morphological volume decreased by 48% between MRI and histology, highlighting the presence of additional tissue-level shrinkage (e.g. an increase in interstitial cleft space). The ratio of pixels classified as containing myocytes to pixels identified as non-myocytes was roughly 6:1 (61.6 vs. 9.8%; the remaining fraction of 28.6% was ‘undefined’). Conclusion Qualitative and quantitative differentiation between myocytes and connective tissue, using state-of-the-art high-resolution serial histology techniques, allows identification of cell-type distribution in whole-heart datasets. Comparison with MRI illustrates a pronounced reduction in anatomical and morphological volumes during histology processing. PMID:25362175

Imaging of extracellular vesicles derived from human bone marrow mesenchymal stem cells using fluorescent and magnetic labels.

PubMed

Dabrowska, Sylwia; Del Fattore, Andrea; Karnas, Elzbieta; Frontczak-Baniewicz, Malgorzata; Kozlowska, Hanna; Muraca, Maurizio; Janowski, Miroslaw; Lukomska, Barbara

2018-01-01

Mesenchymal stem cells have been shown therapeutic in various neurological disorders. Recent studies support the notion that the predominant mechanism by which MSCs act is through the release of extracellular vesicles (EVs). EVs seem to have similar therapeutic activity as their cellular counterparts and may represent an interesting alternative standalone therapy for various diseases. The aim of the study was to optimize the method of EV imaging to better understand therapeutic effects mediated by EVs. The fluorescent lipophilic stain PKH26 and superparamagnetic iron oxide nanoparticles conjugated with rhodamine (Molday ION Rhodamine B™) were used for the labeling of vesicles in human bone marrow MSCs (hBM-MSCs). The entire cycle from intracellular vesicles to EVs followed by their uptake by hBM-MSCs has been studied. The identity of vesicles has been proven by antibodies against: anti-CD9, -CD63, and -CD81 (tetraspanins). NanoSight particle tracking analysis (NTA), high-resolution flow cytometric analysis, transmission electron microscopy (TEM), ELYRA PS.1 super-resolution microscopy, and magnetic resonance imaging (MRI) were used for the characterization of vesicles. The PKH26 and Molday ION were exclusively localized in intracellular vesicles positively stained for EV markers: CD9, CD63, and CD81. The isolated EVs represent heterogeneous population of various sizes as confirmed by NTA. The TEM and MRI were capable to show successful labeling of EVs using ION. Co-culture of EVs with hBM-MSCs revealed their uptake by cells in vitro, as visualized by the co-localization of PKH26 or Molday ION with tetraspanins inside hBM-MSCs. PKH26 and Molday ION seem to be biocompatible with EVs, and the labeling did not interfere with the capability of EVs to re-enter hBM-MSCs during co-culture in vitro. Magnetic properties of IONs provide an additional advantage for the imaging of EV using TEM and MRI.

Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers.

PubMed

Al Faraj, Achraf; Shaik, Asma Sultana; Afzal, Sibtain; Al-Muhsen, Saleh; Halwani, Rabih

2016-05-01

Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti-IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free-breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre-clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra-short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti-IL4Rα-conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers' colocalizations with the inflammatory sites in the lung of ovalbumin-challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Tracing Activity Across the Whole Brain Neural Network with Optogenetic Functional Magnetic Resonance Imaging

PubMed Central

Lee, Jin Hyung

2011-01-01

Despite the overwhelming need, there has been a relatively large gap in our ability to trace network level activity across the brain. The complex dense wiring of the brain makes it extremely challenging to understand cell-type specific activity and their communication beyond a few synapses. Recent development of the optogenetic functional magnetic resonance imaging (ofMRI) provides a new impetus for the study of brain circuits by enabling causal tracing of activities arising from defined cell types and firing patterns across the whole brain. Brain circuit elements can be selectively triggered based on their genetic identity, cell body location, and/or their axonal projection target with temporal precision while the resulting network response is monitored non-invasively with unprecedented spatial and temporal accuracy. With further studies including technological innovations to bring ofMRI to its full potential, ofMRI is expected to play an important role in our system-level understanding of the brain circuit mechanism. PMID:22046160

An analysis of particle track effects on solid mammalian tissues

NASA Technical Reports Server (NTRS)

Todd, P.; Clarkson, T. W. (Principal Investigator)

1992-01-01

Relative biological effectiveness (RBE) and quality factor (Q) at extreme values of linear energy transfer (LET) have been determined on the basis of experiments with single-cell systems and specific tissue responses. In typical single-cell systems, each heavy particle (Ar or Fe) passes through a single cell or no cell. In experiments on animal tissues, however, each heavy particle passes through several cells, and the LET can exceed 200 keV micrometers-1 in every cell. In most laboratory animal tissue systems, however, only a small portion of the hit cells are capable of expressing the end-point being measured, such as cell killing, mutation or carcinogenesis. The following question was therefore addressed: do RBEs and Q factors derived from single-cell experiments properly account for the damage at high LET when multiple cells are hit by HZE tracks? A review is offered in which measured radiation effects and known tissue properties are combined to estimate on the one hand, the number of cells at risk, p3n, per track, where n is the number of cells per track based on tissue and organ geometry, and p3 is the probability that a cell in the track is capable of expressing the experimental end-point. On the other hand, the tissue and single-cell responses are compared by determining the ratio RBE in tissue/RBE in corresponding single cells. Experimental data from the literature indicate that tissue RBEs at very high LET (Fe and Ar ions) are higher than corresponding single-cell RBEs, especially in tissues in which p3n is high.

Nanosized cancer cell-targeted polymeric immunomicelles loaded with superparamagnetic iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Sawant, Rishikesh M.; Sawant, Rupa R.; Gultepe, Evin; Nagesha, Dattatri; Papahadjopoulos-Sternberg, Brigitte; Sridhar, Srinivas; Torchilin, Vladimir P.

2009-10-01

Stable 30-50 nm polymeric polyethylene glycol-phosphatidylethanolamine (PEG-PE)-based micelles entrapping superparamagnetic iron oxide nanoparticles (SPION) have been prepared. At similar concentrations of SPION, the SPION-micelles had significantly better magnetic resonance imaging (MRI) T2 relaxation signal compared to `plain' SPION. Freeze-fracture electron microscopy confirmed SPION entrapment in the lipid core of the PEG-PE micelles. To enhance the targeting capability of these micelles, their surface was modified with the cancer cell-specific anti-nucleosome monoclonal antibody 2C5 (mAb 2C5). Such mAb 2C5-SPION immunomicelles demonstrated specific binding with cancer cells in vitro and were able to bring more SPION to the cancer cells thus demonstrating the potential to be used as targeted MRI contrast agents for tumor imaging.

Mapping immune cell infiltration using restricted diffusion MRI.

PubMed

Yeh, Fang-Cheng; Liu, Li; Hitchens, T Kevin; Wu, Yijen L

2017-02-01

Diffusion MRI provides a noninvasive way to assess tissue microstructure. Based on diffusion MRI, we propose a model-free method called restricted diffusion imaging (RDI) to quantify restricted diffusion and correlate it with cellularity. An analytical relation between q-space signals and the density of restricted spins was derived to quantify restricted diffusion. A phantom study was conducted to investigate the performance of RDI, and RDI was applied to an animal study to assess immune cell infiltration in myocardial tissues with ischemia-reperfusion injury. Our phantom study showed a correlation coefficient of 0.998 between cell density and the restricted diffusion quantified by RDI. The animal study also showed that the high-value regions in RDI matched well with the macrophage infiltration areas in the H&E stained slides. In comparison with diffusion tensor imaging (DTI), RDI exhibited its outperformance to detect macrophage infiltration and delineate inflammatory myocardium. RDI can be used to reveal cell density and detect immune cell infiltration. RDI exhibits better specificity than the diffusivity measurement derived from DTI. Magn Reson Med 77:603-612, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Quantifying the degree of persistence in random amoeboid motion based on the Hurst exponent of fractional Brownian motion.

PubMed

Makarava, Natallia; Menz, Stephan; Theves, Matthias; Huisinga, Wilhelm; Beta, Carsten; Holschneider, Matthias

2014-10-01

Amoebae explore their environment in a random way, unless external cues like, e.g., nutrients, bias their motion. Even in the absence of cues, however, experimental cell tracks show some degree of persistence. In this paper, we analyzed individual cell tracks in the framework of a linear mixed effects model, where each track is modeled by a fractional Brownian motion, i.e., a Gaussian process exhibiting a long-term correlation structure superposed on a linear trend. The degree of persistence was quantified by the Hurst exponent of fractional Brownian motion. Our analysis of experimental cell tracks of the amoeba Dictyostelium discoideum showed a persistent movement for the majority of tracks. Employing a sliding window approach, we estimated the variations of the Hurst exponent over time, which allowed us to identify points in time, where the correlation structure was distorted ("outliers"). Coarse graining of track data via down-sampling allowed us to identify the dependence of persistence on the spatial scale. While one would expect the (mode of the) Hurst exponent to be constant on different temporal scales due to the self-similarity property of fractional Brownian motion, we observed a trend towards stronger persistence for the down-sampled cell tracks indicating stronger persistence on larger time scales.

Comparative analyses identify molecular signature of MRI-classified SVZ-associated glioblastoma

PubMed Central

Lin, Chin-Hsing Annie; Rhodes, Christopher T.; Lin, ChenWei; Phillips, Joanna J.; Berger, Mitchel S.

2017-01-01

ABSTRACT Glioblastoma (GBM) is a highly aggressive brain cancer with limited therapeutic options. While efforts to identify genes responsible for GBM have revealed mutations and aberrant gene expression associated with distinct types of GBM, patients with GBM are often diagnosed and classified based on MRI features. Therefore, we seek to identify molecular representatives in parallel with MRI classification for group I and group II primary GBM associated with the subventricular zone (SVZ). As group I and II GBM contain stem-like signature, we compared gene expression profiles between these 2 groups of primary GBM and endogenous neural stem progenitor cells to reveal dysregulation of cell cycle, chromatin status, cellular morphogenesis, and signaling pathways in these 2 types of MRI-classified GBM. In the absence of IDH mutation, several genes associated with metabolism are differentially expressed in these subtypes of primary GBM, implicating metabolic reprogramming occurs in tumor microenvironment. Furthermore, histone lysine methyltransferase EZH2 was upregulated while histone lysine demethylases KDM2 and KDM4 were downregulated in both group I and II primary GBM. Lastly, we identified 9 common genes across large data sets of gene expression profiles among MRI-classified group I/II GBM, a large cohort of GBM subtypes from TCGA, and glioma stem cells by unsupervised clustering comparison. These commonly upregulated genes have known functions in cell cycle, centromere assembly, chromosome segregation, and mitotic progression. Our findings highlight altered expression of genes important in chromosome integrity across all GBM, suggesting a common mechanism of disrupted fidelity of chromosome structure in GBM. PMID:28278055

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

PubMed Central

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

2016-01-01

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

Mass diffusion coefficient measurement for vitreous humor using FEM and MRI

NASA Astrophysics Data System (ADS)

Rattanakijsuntorn, Komsan; Penkova, Anita; Sadha, Satwindar S.

2018-01-01

In early studies, the ‘contour method’ for determining the diffusion coefficient of the vitreous humor was developed. This technique relied on careful injection of an MRI contrast agent (surrogate drug) into the vitreous humor of fresh bovine eyes, and tracking the contours of the contrast agent in time. In addition, an analytical solution was developed for the theoretical contours built on point source model for the injected surrogate drug. The match between theoretical and experimental contours as a least square fit, while floating the diffusion coefficient, led to the value of the diffusion coefficient. This method had its limitation that the initial injection of the surrogate had to be spherical or ellipsoidal because of the analytical result based on the point-source model. With a new finite element model for the analysis in this study, the technique is much less restrictive and handles irregular shapes of the initial bolus. The fresh bovine eyes were used for drug diffusion study in the vitreous and three contrast agents of different molecular masses: gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA, 938 Da), non-ionic gadoteridol (Prohance, 559 Da), and bovine albumin conjugated with gadolinium (Galbumin, 74 kDa) were used as drug surrogates to visualize the diffusion process by MRI. The 3D finite element model was developed to determine the diffusion coefficients of these surrogates with the images from MRI. This method can be used for other types of bioporous media provided the concentration profile can be visualized (by methods such as MRI or fluorescence).

Tracking Organs Composed of One or Multiple Regions Using Geodesic Active Region Models

NASA Astrophysics Data System (ADS)

Martínez, A.; Jiménez, J. J.

In radiotherapy treatment it is very important to find out the target organs on the medical image sequence in order to determine and apply the proper dose. The techniques to achieve this goal can be classified into extrinsic and intrinsic. Intrinsic techniques only use image processing with medical images associated to the radiotherapy Radiotherapy treatment, as we deal in this chapter. To accurately perform this organ tracking it is necessary to find out segmentation and tracking models that were able to be applied to several image modalities involved on a radiotherapy session (CT CT See Modality , MRI Magnetic resoance imaging , etc.). The movements of the organs are mainly affected by two factors: breathing and involuntary movements associated with the internal organs or patient positioning. Among the several alternatives to track the organs of interest, a model based on geodesic active regions is proposed. This model has been tested over CT Computed tomography images from the pelvic, cardiac, and thoracic area. A new model for the segmentation of organs composed by more than one region is proposed.

Automatic tracking of red blood cells in micro channels using OpenCV

NASA Astrophysics Data System (ADS)

Rodrigues, Vânia; Rodrigues, Pedro J.; Pereira, Ana I.; Lima, Rui

2013-10-01

The present study aims to developan automatic method able to track red blood cells (RBCs) trajectories flowing through a microchannel using the Open Source Computer Vision (OpenCV). The developed method is based on optical flux calculation assisted by the maximization of the template-matching product. The experimental results show a good functional performance of this method.

Tracking children's mental states while solving algebra equations.

PubMed

Anderson, John R; Betts, Shawn; Ferris, Jennifer L; Fincham, Jon M

2012-11-01

Behavioral and function magnetic resonance imagery (fMRI) data were combined to infer the mental states of students as they interacted with an intelligent tutoring system. Sixteen children interacted with a computer tutor for solving linear equations over a six-day period (days 0-5), with days 1 and 5 occurring in an fMRI scanner. Hidden Markov model algorithms combined a model of student behavior with multi-voxel imaging pattern data to predict the mental states of students. We separately assessed the algorithms' ability to predict which step in a problem-solving sequence was performed and whether the step was performed correctly. For day 1, the data patterns of other students were used to predict the mental states of a target student. These predictions were improved on day 5 by adding information about the target student's behavioral and imaging data from day 1. Successful tracking of mental states depended on using the combination of a behavioral model and multi-voxel pattern analysis, illustrating the effectiveness of an integrated approach to tracking the cognition of individuals in real time as they perform complex tasks. Copyright © 2011 Wiley Periodicals, Inc.

Magnetic Resonance Imaging of Mitochondrial Dysfunction and Metabolic Activity, Accompanied by Overproduction of Superoxide.

PubMed

Bakalova, Rumiana; Georgieva, Ekaterina; Ivanova, Donika; Zhelev, Zhivko; Aoki, Ichio; Saga, Tsuneo

2015-12-16

This study shows that a mitochondria-penetrating nitroxide probe (mito-TEMPO) allows detection of superoxide and visualization of mitochondrial dysfunction in living cells due to the effect of T1 shortening in MRI. Mitochondrial dysfunction was induced by treatment of cells with rotenone and 2-methoxyestradiol (2-ME/Rot). The MRI measurements were performed on 7T MRI. The 2-ME/Rot-treated cells were characterized by overproduction of superoxide, which was confirmed by a conventional dihydroethidium test. In the presence of mito-TEMPO, the intensity of MRI signal in 2-ME/Rot-treated cells was ∼30-40% higher, in comparison with that in untreated cells or culture media. In model (cell-free) systems, we observed that superoxide, but not hydrogen peroxide, increased the intensity of T1-weighted MRI signal of mito-TEMPO. Moreover, the superoxide restores the T1-weighted MRI contrast of mito-TEMPOH, a noncontrast (diamagnetic) analogue of mito-TEMPO. This was also confirmed by using EPR spectroscopy. The results demonstrate that superoxide radical is involved in the enhancement of T1-weighted MRI contrast in living cells, in the absence and presence of mito-TEMPO. This report gives a direction for discovering new opportunities for functional MRI, for detection of metabolic activity, accompanied by overproduction of superoxide, as well as by disturbance of the balance between superoxide and hydrogen peroxide, a very important approach to clarify the fine molecular mechanisms in the regulation of many pathologies. The visualization of mitochondrial activity in real-time can be crucial to clarify the molecular mechanism of the functional MRI in its commonly accepted definition, as a method for detection of neurovascular coupling.

WSR-88D Cell Trends

NASA Technical Reports Server (NTRS)

Wheeler, Mark M.

1998-01-01

This report documents the Applied Meteorology Unit's evaluation of the Cell Trends display as a tool for radar operators to use in their evaluation of storm cell strength. The objective of the evaluation is to assess the utility of the WSR-88D graphical Cell Trends display for local radar cell interpretation in support of the 45th Weather Squadron (45 WS), Spaceflight Meteorology Group (SMG), and National Weather Service (NWS) Melbourne (MLB) operational requirements. The analysis procedure was to identify each cell and track the maximum reflectivity, height of maximum reflectivity, storm top, storm base, hail and severe hail probability, cell-based Vertically Integrated Liquid (VIL) and core aspect ratio using WATADS Build 9.0 cell trends information. One problem noted in the analysis phase was that the Storm Cell Identification and Tracking (SCIT) algorithm had a difficult time tracking the small cells associated with the Florida weather regimes. The analysis indicated numerous occasions when a cell track would end or an existing cell would be give a new ID in the middle of its life cycle. This investigation has found that most cells, which produce hail or microburst events, have discernable Cell Trends signatures. Forecasters should monitor the PUP's Cell Trends display for cells that show rapid (1 scan) changes in both the heights of maximum reflectivity and cell-based VIEL. It is important to note that this a very limited data set (four case days). Fifty-two storm cells were analyzed during those four days. The above mentioned t=ds, increase in the two cell attributes for hail events and decrease in the two cell attributes for wind events were noted in most of the cells. The probability of detection was 88% for both events. The False Alarm Rate (FAR) was a 36% for hail events and a respectable 25% for microburst events. In addition the Heidke Skill Score (HSS) is 0.65 for hail events and 0.67 for microburst events. For random forecast the HSS is 0 and that a perfect score is 1.

Magnetic Particle Spectroscopy Reveals Dynamic Changes in the Magnetic Behavior of Very Small Superparamagnetic Iron Oxide Nanoparticles During Cellular Uptake and Enables Determination of Cell-Labeling Efficacy.

PubMed

Poller, Wolfram C; Löwa, Norbert; Wiekhorst, Frank; Taupitz, Matthias; Wagner, Susanne; Möller, Konstantin; Baumann, Gert; Stangl, Verena; Trahms, Lutz; Ludwig, Antje

2016-02-01

In vivo tracking of nanoparticle-labeled cells by magnetic resonance imaging (MRI) crucially depends on accurate determination of cell-labeling efficacy prior to transplantation. Here, we analyzed the feasibility and accuracy of magnetic particle spectroscopy (MPS) for estimation of cell-labeling efficacy in living THP-1 cells incubated with very small superparamagnetic iron oxide nanoparticles (VSOP). Cell viability and proliferation capacity were not affected by the MPS measurement procedure. In VSOP samples without cell contact, MPS enabled highly accurate quantification. In contrast, MPS constantly overestimated the amount of cell associated and internalized VSOP. Analyses of the MPS spectrum shape expressed as harmonic ratio A₅/A₃ revealed distinct changes in the magnetic behavior of VSOP in response to cellular uptake. These changes were proportional to the deviation between MPS and actual iron amount, therefore allowing for adjusted iron quantification. Transmission electron microscopy provided visual evidence that changes in the magnetic properties correlated with cell surface interaction of VSOP as well as with alterations of particle structure and arrangement during the phagocytic process. Altogether, A₅/A₃-adjusted MPS enables highly accurate, cell-preserving VSOP quantification and furthermore provides information on the magnetic characteristics of internalized VSOP.

Bioluminescent magnetic nanoparticles as potential imaging agents for mammalian spermatozoa.

PubMed

Vasquez, Erick S; Feugang, Jean M; Willard, Scott T; Ryan, Peter L; Walters, Keisha B

2016-03-17

Nanoparticles have emerged as key materials for developing applications in nanomedicine, nanobiotechnology, bioimaging and theranostics. Existing bioimaging technologies include bioluminescent resonance energy transfer-conjugated quantum dots (BRET-QDs). Despite the current use of BRET-QDs for bioimaging, there are strong concerns about QD nanocomposites containing cadmium which exhibits potential cellular toxicity. In this study, bioluminescent composites comprised of magnetic nanoparticles and firefly luciferase (Photinus pyralis) are examined as potential light-emitting agents for imaging, detection, and tracking mammalian spermatozoa. Characterization was carried out using infrared spectroscopy, TEM and cryo-TEM imaging, and ζ-potential measurements to demonstrate the successful preparation of these nanocomposites. Binding interactions between the synthesized nanoparticles and spermatozoon were characterized using confocal and atomic/magnetic force microscopy. Bioluminescence imaging and UV-visible-NIR microscopy results showed light emission from sperm samples incubated with the firefly luciferase-modified nanoparticles. Therefore, these newly synthesized luciferase-modified magnetic nanoparticles show promise as substitutes for QD labeling, and can potentially also be used for in vivo manipulation and tracking, as well as MRI techniques. These preliminary data indicate that luciferase-magnetic nanoparticle composites can potentially be used for spermatozoa detection and imaging. Their magnetic properties add additional functionality to allow for manipulation, sorting, or tracking of cells using magnetic techniques.

Phase 0 Trial of Itraconazole for Early-Stage Non-Small Cell Lung Cancer

DTIC Science & Technology

2016-10-01

tissue and blood sampling in addition to magnetic resonance imaging ( MRI ) scans for biomarker analysis. At the time of surgery, resected tissue will...original proposal, these subjects underwent study-related MRI scans, skin biopsies, blood tests, treatment with itraconazole, and surgical resection...not complete serial MRIs scans. Task 2: Determine anti-angiogenic effects of itraconazole Subtask 2a: Blood-based PD studies As described in the

Quantitative MRI and spectroscopy of bone marrow

PubMed Central

Ruschke, Stefan; Dieckmeyer, Michael; Diefenbach, Maximilian; Franz, Daniela; Gersing, Alexandra S.; Krug, Roland; Baum, Thomas

2017-01-01

Bone marrow is one of the largest organs in the human body, enclosing adipocytes, hematopoietic stem cells, which are responsible for blood cell production, and mesenchymal stem cells, which are responsible for the production of adipocytes and bone cells. Magnetic resonance imaging (MRI) is the ideal imaging modality to monitor bone marrow changes in healthy and pathological states, thanks to its inherent rich soft‐tissue contrast. Quantitative bone marrow MRI and magnetic resonance spectroscopy (MRS) techniques have been also developed in order to quantify changes in bone marrow water–fat composition, cellularity and perfusion in different pathologies, and to assist in understanding the role of bone marrow in the pathophysiology of systemic diseases (e.g. osteoporosis). The present review summarizes a large selection of studies published until March 2017 in proton‐based quantitative MRI and MRS of bone marrow. Some basic knowledge about bone marrow anatomy and physiology is first reviewed. The most important technical aspects of quantitative MR methods measuring bone marrow water–fat composition, fatty acid composition, perfusion, and diffusion are then described. Finally, previous MR studies are reviewed on the application of quantitative MR techniques in both healthy aging and diseased bone marrow affected by osteoporosis, fractures, metabolic diseases, multiple myeloma, and bone metastases. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:332–353. PMID:28570033

Multilevel Space-Time Aggregation for Bright Field Cell Microscopy Segmentation and Tracking

PubMed Central

Inglis, Tiffany; De Sterck, Hans; Sanders, Geoffrey; Djambazian, Haig; Sladek, Robert; Sundararajan, Saravanan; Hudson, Thomas J.

2010-01-01

A multilevel aggregation method is applied to the problem of segmenting live cell bright field microscope images. The method employed is a variant of the so-called “Segmentation by Weighted Aggregation” technique, which itself is based on Algebraic Multigrid methods. The variant of the method used is described in detail, and it is explained how it is tailored to the application at hand. In particular, a new scale-invariant “saliency measure” is proposed for deciding when aggregates of pixels constitute salient segments that should not be grouped further. It is shown how segmentation based on multilevel intensity similarity alone does not lead to satisfactory results for bright field cells. However, the addition of multilevel intensity variance (as a measure of texture) to the feature vector of each aggregate leads to correct cell segmentation. Preliminary results are presented for applying the multilevel aggregation algorithm in space time to temporal sequences of microscope images, with the goal of obtaining space-time segments (“object tunnels”) that track individual cells. The advantages and drawbacks of the space-time aggregation approach for segmentation and tracking of live cells in sequences of bright field microscope images are presented, along with a discussion on how this approach may be used in the future work as a building block in a complete and robust segmentation and tracking system. PMID:20467468

Simultaneous GCaMP6-based fiber photometry and fMRI in rats.

PubMed

Liang, Zhifeng; Ma, Yuncong; Watson, Glenn D R; Zhang, Nanyin

2017-09-01

Understanding the relationship between neural and vascular signals is essential for interpretation of functional MRI (fMRI) results with respect to underlying neuronal activity. Simultaneously measuring neural activity using electrophysiology with fMRI has been highly valuable in elucidating the neural basis of the blood oxygenation-level dependent (BOLD) signal. However, this approach is also technically challenging due to the electromagnetic interference that is observed in electrophysiological recordings during MRI scanning. Recording optical correlates of neural activity, such as calcium signals, avoids this issue, and has opened a new avenue to simultaneously acquire neural and BOLD signals. The present study is the first to demonstrate the feasibility of simultaneously and repeatedly acquiring calcium and BOLD signals in animals using a genetically encoded calcium indicator, GCaMP6. This approach was validated with a visual stimulation experiment, during which robust increases of both calcium and BOLD signals in the superior colliculus were observed. In addition, repeated measurement in the same animal demonstrated reproducible calcium and BOLD responses to the same stimuli. Taken together, simultaneous GCaMP6-based fiber photometry and fMRI recording presents a novel, artifact-free approach to simultaneously measuring neural and fMRI signals. Furthermore, given the cell-type specificity of GCaMP6, this approach has the potential to mechanistically dissect the contributions of individual neuron populations to BOLD signal, and ultimately reveal its underlying neural mechanisms. The current study established the method for simultaneous GCaMP6-based fiber photometry and fMRI in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Improving a free air breathing proton exchange membrane fuel cell through the Maximum Efficiency Point Tracking method

NASA Astrophysics Data System (ADS)

Higuita Cano, Mauricio; Mousli, Mohamed Islam Aniss; Kelouwani, Sousso; Agbossou, Kodjo; Hammoudi, Mhamed; Dubé, Yves

2017-03-01

This work investigates the design and validation of a fuel cell management system (FCMS) which can perform when the fuel cell is at water freezing temperature. This FCMS is based on a new tracking technique with intelligent prediction, which combined the Maximum Efficiency Point Tracking with variable perturbation-current step and the fuzzy logic technique (MEPT-FL). Unlike conventional fuel cell control systems, our proposed FCMS considers the cold-weather conditions, the reduction of fuel cell set-point oscillations. In addition, the FCMS is built to respond quickly and effectively to the variations of electric load. A temperature controller stage is designed in conjunction with the MEPT-FL in order to operate the FC at low-temperature values whilst tracking at the same time the maximum efficiency point. The simulation results have as well experimental validation suggest that propose approach is effective and can achieve an average efficiency improvement up to 8%. The MEPT-FL is validated using a Proton Exchange Membrane Fuel Cell (PEMFC) of 500 W.

Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

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

Zhu, Changlian; Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University; Gao, Jianfeng

2011-01-07

Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI),more » could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.« less

Weed or Wheel! fMRI, Behavioural, and Toxicological Investigations of How Cannabis Smoking Affects Skills Necessary for Driving

PubMed Central

Thomas, Aurélien; Mall, Jean-Frédéric; Chtioui, Haithem; Appenzeller, Monique; Annoni, Jean-Marie; Favrat, Bernard

2013-01-01

Marijuana is the most widely used illicit drug, however its effects on cognitive functions underling safe driving remain mostly unexplored. Our goal was to evaluate the impact of cannabis on the driving ability of occasional smokers, by investigating changes in the brain network involved in a tracking task. The subject characteristics, the percentage of Δ9-Tetrahydrocannabinol in the joint, and the inhaled dose were in accordance with real-life conditions. Thirty-one male volunteers were enrolled in this study that includes clinical and toxicological aspects together with functional magnetic resonance imaging of the brain and measurements of psychomotor skills. The fMRI paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition. We show that cannabis smoking, even at low Δ9-Tetrahydrocannabinol blood concentrations, decreases psychomotor skills and alters the activity of the brain networks involved in cognition. The relative decrease of Blood Oxygen Level Dependent response (BOLD) after cannabis smoking in the anterior insula, dorsomedial thalamus, and striatum compared to placebo smoking suggests an alteration of the network involved in saliency detection. In addition, the decrease of BOLD response in the right superior parietal cortex and in the dorsolateral prefrontal cortex indicates the involvement of the Control Executive network known to operate once the saliencies are identified. Furthermore, cannabis increases activity in the rostral anterior cingulate cortex and ventromedial prefrontal cortices, suggesting an increase in self-oriented mental activity. Subjects are more attracted by intrapersonal stimuli (“self”) and fail to attend to task performance, leading to an insufficient allocation of task-oriented resources and to sub-optimal performance. These effects correlate with the subjective feeling of confusion rather than with the blood level of Δ9-Tetrahydrocannabinol. These findings bolster the zero-tolerance policy adopted in several countries that prohibits the presence of any amount of drugs in blood while driving. PMID:23300977

Combined diffusion-weighted, blood oxygen level-dependent, and dynamic contrast-enhanced MRI for characterization and differentiation of renal cell carcinoma.

PubMed

Notohamiprodjo, Mike; Staehler, Michael; Steiner, Nicole; Schwab, Felix; Sourbron, Steven P; Michaely, Henrik J; Helck, Andreas D; Reiser, Maximilian F; Nikolaou, Konstantin

2013-06-01

To investigate a multiparametric magnetic resonance imaging (MRI) approach comprising diffusion-weighted imaging (DWI), blood oxygen-dependent (BOLD), and dynamic contrast-enhanced (DCE) MRI for characterization and differentiation of primary renal cell carcinoma (RCC). Fourteen patients with clear-cell carcinoma and four patients with papillary RCC were examined with DWI, BOLD MRI, and DCE MRI at 1.5T. The apparent diffusion coefficient (ADC) was calculated with a monoexponential decay. The spin-dephasing rate R2* was derived from parametric R2* maps. DCE-MRI was analyzed using a two-compartment exchange model allowing separation of perfusion (plasma flow [FP] and plasma volume [VP]), permeability (permeability surface area product [PS]), and extravascular extracellular volume (VE). Statistical analysis was performed with Wilcoxon signed-rank test, Pearson's correlation coefficient, and receiver operating characteristic curve analysis. Clear-cell RCC showed higher ADC and lower R2* compared to papillary subtypes, but differences were not significant. FP of clear-cell subtypes was significantly higher than in papillary RCC. Perfusion parameters showed moderate but significant inverse correlation with R2*. VE showed moderate inverse correlation with ADC. Fp and Vp showed best sensitivity for histological differentiation. Multiparametric MRI comprising DWI, BOLD, and DCE MRI is feasible for assessment of primary RCC. BOLD moderately correlates to DCE MRI-derived perfusion. ADC shows moderate correlation to the extracellular volume, but does not correlate to tumor oxygenation or perfusion. In this preliminary study DCE-MRI appeared superior to BOLD and DWI for histological differentiation. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

Augmenting intraoperative MRI with preoperative fMRI and DTI by biomechanical simulation of brain deformation

NASA Astrophysics Data System (ADS)

Warfield, Simon K.; Talos, Florin; Kemper, Corey; Cosman, Eric; Tei, Alida; Ferrant, Matthieu; Macq, Benoit M. M.; Wells, William M., III; Black, Peter M.; Jolesz, Ferenc A.; Kikinis, Ron

2003-05-01

The key challenge facing the neurosurgeon during neurosurgery is to be able to remove from the brain as much tumor tissue as possible while preserving healthy tissue and minimizing the disruption of critical anatomical structures. The purpose of this work was to demonstrate the use of biomechanical simulation of brain deformation to project preoperative fMRI and DTI data into the coordinate system of the patient brain deformed during neurosurgery. This projection enhances the visualization of relevant critical structures available to the neurosurgeon. Our approach to tracking brain changes during neurosurgery has been previously described. We applied this procedure to warp preoperative fMRI and DTI to match intraoperative MRI. We constructed visualizations of preoperative fMRI and DTI, and intraoperative MRI showing a close correspondence between the matched data. We have previously demonstrated our biomechanical simulation of brain deformation can be executed entirely during neurosurgery. We previously used a generic atlas as a substitute for patient specific data. Here we report the successful alignment of patient-specific DTI and fMRI preoperative data into the intraoperative configuration of the patient's brain. This can significantly enhance the information available to the neurosurgeon.

Technological advances in real-time tracking of cell death

PubMed Central

Skommer, Joanna; Darzynkiewicz, Zbigniew; Wlodkowic, Donald

2010-01-01

Cell population can be viewed as a quantum system, which like Schrödinger’s cat exists as a combination of survival- and death-allowing states. Tracking and understanding cell-to-cell variability in processes of high spatio-temporal complexity such as cell death is at the core of current systems biology approaches. As probabilistic modeling tools attempt to impute information inaccessible by current experimental approaches, advances in technologies for single-cell imaging and omics (proteomics, genomics, metabolomics) should go hand in hand with the computational efforts. Over the last few years we have made exciting technological advances that allow studies of cell death dynamically in real-time and with the unprecedented accuracy. These approaches are based on innovative fluorescent assays and recombinant proteins, bioelectrical properties of cells, and more recently also on state-of-the-art optical spectroscopy. Here, we review current status of the most innovative analytical technologies for dynamic tracking of cell death, and address the interdisciplinary promises and future challenges of these methods. PMID:20519963

Novel Strategy for Tracking the Microbial Degradation of Azo Dyes with Different Polarities in Living Cells.

PubMed

Liu, Fei; Xu, Meiying; Chen, Xingjuan; Yang, Yonggang; Wang, Haiji; Sun, Guoping

2015-10-06

Direct visualization evidence is important for understanding the microbial degradation mechanisms. To track the microbial degradation pathways of azo dyes with different polar characterizations, sensors based on the fluorescence resonance energy transfer (FRET) from 1,8-naphthalimide to azo dyes were synthesized, in which the quenched fluorescence will recover when the azo bond was cleaved. In living cells, the sensor-tracking experiment showed that the low polarity and hydrophobic azo dye can be taken up into the cells and reduced inside the cells, whereas the high polarity and hydrophilic azo dye can be reduced only outside the cells because of the selective permeability of the cell membranes. These results indicated that there were two different bacterial degradation pathways available for different polarity azo dyes. To our knowledge, no fluorescent sensor has yet been designed for illuminating the microbial degradation mechanisms of organic pollutants with different characteristics.

Application of High-Resolution Magic-Angle Spinning NMR Spectroscopy to Define the Cell Uptake of MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Calabi, Luisella; Alfieri, Goffredo; Biondi, Luca; De Miranda, Mario; Paleari, Lino; Ghelli, Stefano

2002-06-01

A new method, based on proton high-resolution magic-angle spinning ( 1H HR-MAS) NMR spectroscopy, has been employed to study the cell uptake of magnetic resonance imaging contrast agents (MRI-CAs). The method was tested on human red blood cells (HRBC) and white blood cells (HWBC) by using three gadolinium complexes, widely used in diagnostics, Gd-BOPTA, Gd-DTPA, and Gd-DOTA, and the analogous complexes obtained by replacing Gd(III) with Dy(III), Nd(III), and Tb(III) (i.e., complexes isostructural to the ones of gadolinium but acting as shift agents). The method is based on the evaluation of the magnetic effects, line broadening, or induced lanthanide shift (LIS) caused by these complexes on NMR signals of intra- and extracellular water. Since magnetic effects are directly linked to permeability, this method is direct. In all the tests, these magnetic effects were detected for the extracellular water signal only, providing a direct proof that these complexes are not able to cross the cell membrane. Line broadening effects (i.e., the use of gadolinium complexes) only allow qualitative evaluations. On the contrary, LIS effects can be measured with high precision and they can be related to the concentration of the paramagnetic species in the cellular compartments. This is possible because the HR-MAS technique provides the complete elimination of bulk magnetic susceptibility (BMS) shift and the differentiation of extra- and intracellular water signals. Thus with this method, the rapid quantification of the MRI-CA amount inside and outside the cells is actually feasible.

Image fusion pitfalls for cranial radiosurgery

PubMed Central

Jonker, Benjamin P.

2013-01-01

Stereotactic radiosurgery requires imaging to define both the stereotactic space in which the treatment is delivered and the target itself. Image fusion is the process of using rotation and translation to bring a second image set into alignment with the first image set. This allows the potential concurrent use of multiple image sets to define the target and stereotactic space. While a single magnetic resonance imaging (MRI) sequence alone can be used for delineation of the target and fiducials, there may be significant advantages to using additional imaging sets including other MRI sequences, computed tomography (CT) scans, and advanced imaging sets such as catheter-based angiography, diffusor tension imaging-based fiber tracking and positon emission tomography in order to more accurately define the target and surrounding critical structures. Stereotactic space is usually defined by detection of fiducials on the stereotactic head frame or mask system. Unfortunately MRI sequences are susceptible to geometric distortion, whereas CT scans do not face this problem (although they have poorer resolution of the target in most cases). Thus image fusion can allow the definition of stereotactic space to proceed from the geometrically accurate CT images at the same time as using MRI to define the target. The use of image fusion is associated with risk of error introduced by inaccuracies of the fusion process, as well as workflow changes that if not properly accounted for can mislead the treating clinician. The purpose of this review is to describe the uses of image fusion in stereotactic radiosurgery as well as its potential pitfalls. PMID:23682338

Tracking the Re-organization of Motor Functions After Disconnective Surgery: A Longitudinal fMRI and DTI Study

PubMed Central

Rosazza, Cristina; Deleo, Francesco; D'Incerti, Ludovico; Antelmi, Luigi; Tringali, Giovanni; Didato, Giuseppe; Bruzzone, Maria G.; Villani, Flavio; Ghielmetti, Francesco

2018-01-01

Objective: Mechanisms of motor plasticity are critical to maintain motor functions after cerebral damage. This study explores the mechanisms of motor reorganization occurring before and after surgery in four patients with drug-refractory epilepsy candidate to disconnective surgery. Methods: We studied four patients with early damage, who underwent tailored hemispheric surgery in adulthood, removing the cortical motor areas and disconnecting the corticospinal tract (CST) from the affected hemisphere. Motor functions were assessed clinically, with functional MRI (fMRI) tasks of arm and leg movement and Diffusion Tensor Imaging (DTI) before and after surgery with assessments of up to 3 years. Quantifications of fMRI motor activations and DTI fractional anisotropy (FA) color maps were performed to assess the lateralization of motor network. We hypothesized that lateralization of motor circuits assessed preoperatively with fMRI and DTI was useful to evaluate the motor outcome in these patients. Results: In two cases preoperative DTI-tractography did not reconstruct the CST, and FA-maps were strongly asymmetric. In the other two cases, the affected CST appeared reduced compared to the contralateral one, with modest asymmetry in the FA-maps. fMRI showed different degrees of lateralization of the motor network and the SMA of the intact hemisphere was mostly engaged in all cases. After surgery, patients with a strongly lateralized motor network showed a stable performance. By contrast, a patient with a more bilateral pattern showed worsening of the upper limb function. For all cases, fMRI activations shifted to the intact hemisphere. Structural alterations of motor circuits, observed with FA values, continued beyond 1 year after surgery. Conclusion: In our case series fMRI and DTI could track the longitudinal reorganization of motor functions. In these four patients the more the paretic limbs recruited the intact hemisphere in primary motor and associative areas, the greater the chances were of maintaining elementary motor functions after adult surgery. In particular, DTI-tractography and quantification of FA-maps were useful to assess the lateralization of motor network. In these cases reorganization of motor connectivity continued for long time periods after surgery. PMID:29922216

Tracking the Re-organization of Motor Functions After Disconnective Surgery: A Longitudinal fMRI and DTI Study.

PubMed

Rosazza, Cristina; Deleo, Francesco; D'Incerti, Ludovico; Antelmi, Luigi; Tringali, Giovanni; Didato, Giuseppe; Bruzzone, Maria G; Villani, Flavio; Ghielmetti, Francesco

2018-01-01

Objective: Mechanisms of motor plasticity are critical to maintain motor functions after cerebral damage. This study explores the mechanisms of motor reorganization occurring before and after surgery in four patients with drug-refractory epilepsy candidate to disconnective surgery. Methods: We studied four patients with early damage, who underwent tailored hemispheric surgery in adulthood, removing the cortical motor areas and disconnecting the corticospinal tract (CST) from the affected hemisphere. Motor functions were assessed clinically, with functional MRI (fMRI) tasks of arm and leg movement and Diffusion Tensor Imaging (DTI) before and after surgery with assessments of up to 3 years. Quantifications of fMRI motor activations and DTI fractional anisotropy (FA) color maps were performed to assess the lateralization of motor network. We hypothesized that lateralization of motor circuits assessed preoperatively with fMRI and DTI was useful to evaluate the motor outcome in these patients. Results: In two cases preoperative DTI-tractography did not reconstruct the CST, and FA-maps were strongly asymmetric. In the other two cases, the affected CST appeared reduced compared to the contralateral one, with modest asymmetry in the FA-maps. fMRI showed different degrees of lateralization of the motor network and the SMA of the intact hemisphere was mostly engaged in all cases. After surgery, patients with a strongly lateralized motor network showed a stable performance. By contrast, a patient with a more bilateral pattern showed worsening of the upper limb function. For all cases, fMRI activations shifted to the intact hemisphere. Structural alterations of motor circuits, observed with FA values, continued beyond 1 year after surgery. Conclusion: In our case series fMRI and DTI could track the longitudinal reorganization of motor functions. In these four patients the more the paretic limbs recruited the intact hemisphere in primary motor and associative areas, the greater the chances were of maintaining elementary motor functions after adult surgery. In particular, DTI-tractography and quantification of FA-maps were useful to assess the lateralization of motor network. In these cases reorganization of motor connectivity continued for long time periods after surgery.

Influence of salinomycin treatment on division and movement of individual cancer cells cultured in normoxia or hypoxia evaluated with time-lapse digital holographic microscopy

PubMed Central

Kamlund, Sofia; Strand, Daniel; Janicke, Birgit; Alm, Kersti; Oredsson, Stina

2017-01-01

ABSTRACT Most studies on new cancer drugs are based on population-derived data, where the absence of response of a small population may pass unnoticed. Thus, individual longitudinal tracking of cells is important for the future development of efficient cancer treatments. We have used digital holographic microscopy to track individual JIMT-1 human breast cancer cells and L929 mouse fibroblast cultivated in normoxia or hypoxia. In addition, JIMT-1 cells were treated with salinomycin, a cancer stem cell targeting compound. Three-day time-lapse movies were captured and individual cells were analysed with respect to cell division (cell cycle length) and cell movement. Comparing population-doubling time derived from population-based growth curves and individual cell cycle time data from time-lapse movies show that the former hide a sub-population of dividing cells. Salinomycin treatment increased the motility of cells, however, this motility did not result in an increased distant migration i.e. the cells increased their local movement. MCF-7 breast cancer cells showed similar motility behaviour as salinomycin-treated JIMT-1 cells. We suggest that combining features, such as motility and migration, can be used to distinguish cancer cells with mesenchymal (JIMT-1) and epithelial (MCF-7) features. The data clearly emphasize the importance of longitudinal cell tracking to understand the biology of individual cells under different conditions. PMID:28933990

Improved brain tumor segmentation by utilizing tumor growth model in longitudinal brain MRI

NASA Astrophysics Data System (ADS)

Pei, Linmin; Reza, Syed M. S.; Li, Wei; Davatzikos, Christos; Iftekharuddin, Khan M.

2017-03-01

In this work, we propose a novel method to improve texture based tumor segmentation by fusing cell density patterns that are generated from tumor growth modeling. To model tumor growth, we solve the reaction-diffusion equation by using Lattice-Boltzmann method (LBM). Computational tumor growth modeling obtains the cell density distribution that potentially indicates the predicted tissue locations in the brain over time. The density patterns is then considered as novel features along with other texture (such as fractal, and multifractal Brownian motion (mBm)), and intensity features in MRI for improved brain tumor segmentation. We evaluate the proposed method with about one hundred longitudinal MRI scans from five patients obtained from public BRATS 2015 data set, validated by the ground truth. The result shows significant improvement of complete tumor segmentation using ANOVA analysis for five patients in longitudinal MR images.

Improved brain tumor segmentation by utilizing tumor growth model in longitudinal brain MRI.

PubMed

Pei, Linmin; Reza, Syed M S; Li, Wei; Davatzikos, Christos; Iftekharuddin, Khan M

2017-02-11

In this work, we propose a novel method to improve texture based tumor segmentation by fusing cell density patterns that are generated from tumor growth modeling. In order to model tumor growth, we solve the reaction-diffusion equation by using Lattice-Boltzmann method (LBM). Computational tumor growth modeling obtains the cell density distribution that potentially indicates the predicted tissue locations in the brain over time. The density patterns is then considered as novel features along with other texture (such as fractal, and multifractal Brownian motion (mBm)), and intensity features in MRI for improved brain tumor segmentation. We evaluate the proposed method with about one hundred longitudinal MRI scans from five patients obtained from public BRATS 2015 data set, validated by the ground truth. The result shows significant improvement of complete tumor segmentation using ANOVA analysis for five patients in longitudinal MR images.

Tract-based Spatial Statistics and fMRI Analysis in Patients with Small Cell Lung Cancer before Prophylactic Cranial Irradiation

NASA Astrophysics Data System (ADS)

Benezi, S.; Bromis, K.; Karavasilis, E.; Karanasiou, I. S.; Koutsoupidou, M.; Matsopoulos, G.; Ventouras, E.; Uzunoglu, N.; Kouloulias, V.; Papathanasiou, M.; Foteineas, A.; Efstathopoulos, E.; Kelekis, N.; Kelekis, D.

2015-09-01

Prophylactic cranial irradiation (PCI) is known to increase life expectancy to a significant degree in Small Cell Lung Cancer (SCLC) patients. The overall scope of this research is to investigate changes in structural and functional connectivity between SCLC patients and controls before and after PCI treatment. In the current study specifically we use diffusion tensor imaging (DTI) and functional Magnetic Resonance (fMRI) to identify potential alterations in white matter structure and brain function respectively, in SCLC patients before PCI compared to healthy participants. The results in DTI analysis have showed lower fractional anisotropy (FA) and higher eigenvalues in white matter regions in the patient group. Similarly, in fMRI analysis a lower level of activation in the primary somatosensory cortex was reported. The results presented herein are subject to further investigation with larger patient and control groups.

Magnetic resonance imaging of tablet dissolution.

PubMed

Nott, Kevin P

2010-01-01

Magnetic resonance imaging (MRI) is the technique of choice for measuring hydration, and its effects, during dissolution of tablets since it non-invasively maps (1)H nuclei associated with 'mobile' water. Although most studies have used MRI systems with high-field superconducting magnets, low-field laboratory-based instruments based on permanent magnet technology are being developed that provide key data for the formulation scientist. Incorporation of dissolution hardware, in particular the United States Pharmacopeia (USP) apparatus 4 flow-through cell, allows measurements under controlled conditions for comparison against other dissolution methods. Furthermore, simultaneous image acquisition and measurement of drug concentration allow direct comparison of the drug release throughout the hydration process. The combination of low-field MRI with USP-4 apparatus provides another tool to aid tablet formulation. Copyright 2009 Elsevier B.V. All rights reserved.

TrackMate: An open and extensible platform for single-particle tracking.

PubMed

Tinevez, Jean-Yves; Perry, Nick; Schindelin, Johannes; Hoopes, Genevieve M; Reynolds, Gregory D; Laplantine, Emmanuel; Bednarek, Sebastian Y; Shorte, Spencer L; Eliceiri, Kevin W

2017-02-15

We present TrackMate, an open source Fiji plugin for the automated, semi-automated, and manual tracking of single-particles. It offers a versatile and modular solution that works out of the box for end users, through a simple and intuitive user interface. It is also easily scriptable and adaptable, operating equally well on 1D over time, 2D over time, 3D over time, or other single and multi-channel image variants. TrackMate provides several visualization and analysis tools that aid in assessing the relevance of results. The utility of TrackMate is further enhanced through its ability to be readily customized to meet specific tracking problems. TrackMate is an extensible platform where developers can easily write their own detection, particle linking, visualization or analysis algorithms within the TrackMate environment. This evolving framework provides researchers with the opportunity to quickly develop and optimize new algorithms based on existing TrackMate modules without the need of having to write de novo user interfaces, including visualization, analysis and exporting tools. The current capabilities of TrackMate are presented in the context of three different biological problems. First, we perform Caenorhabditis-elegans lineage analysis to assess how light-induced damage during imaging impairs its early development. Our TrackMate-based lineage analysis indicates the lack of a cell-specific light-sensitive mechanism. Second, we investigate the recruitment of NEMO (NF-κB essential modulator) clusters in fibroblasts after stimulation by the cytokine IL-1 and show that photodamage can generate artifacts in the shape of TrackMate characterized movements that confuse motility analysis. Finally, we validate the use of TrackMate for quantitative lifetime analysis of clathrin-mediated endocytosis in plant cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Multicell migration tracking within angiogenic networks by deep learning-based segmentation and augmented Bayesian filtering.

PubMed

Wang, Mengmeng; Ong, Lee-Ling Sharon; Dauwels, Justin; Asada, H Harry

2018-04-01

Cell migration is a key feature for living organisms. Image analysis tools are useful in studying cell migration in three-dimensional (3-D) in vitro environments. We consider angiogenic vessels formed in 3-D microfluidic devices (MFDs) and develop an image analysis system to extract cell behaviors from experimental phase-contrast microscopy image sequences. The proposed system initializes tracks with the end-point confocal nuclei coordinates. We apply convolutional neural networks to detect cell candidates and combine backward Kalman filtering with multiple hypothesis tracking to link the cell candidates at each time step. These hypotheses incorporate prior knowledge on vessel formation and cell proliferation rates. The association accuracy reaches 86.4% for the proposed algorithm, indicating that the proposed system is able to associate cells more accurately than existing approaches. Cell culture experiments in 3-D MFDs have shown considerable promise for improving biology research. The proposed system is expected to be a useful quantitative tool for potential microscopy problems of MFDs.

Personalized nanomedicine advancements for stem cell tracking☆

PubMed Central

Janowski, Mirek; Bulte, Jeff W.M.; Walczak, Piotr

2012-01-01

Recent technological developments in biomedicine have facilitated the generation of data on the anatomical, physiological and molecular level for individual patients and thus introduces opportunity for therapy to be personalized in an unprecedented fashion. Generation of patient-specific stem cells exemplifies the efforts toward this new approach. Cell-based therapy is a highly promising treatment paradigm; however, due to the lack of consistent and unbiased data about the fate of stem cells in vivo, interpretation of therapeutic remains challenging hampering the progress in this field. The advent of nanotechnology with a wide palette of inorganic and organic nanostructures has expanded the arsenal of methods for tracking transplanted stem cells. The diversity of nanomaterials has revolutionized personalized nanomedicine and enables individualized tailoring of stem cell labeling materials for the specific needs of each patient. The successful implementation of stem cell tracking will likely be a significant driving force that will contribute to the further development of nanotheranostics. The purpose of this review is to emphasize the role of cell tracking using currently available nanoparticles. PMID:22820528

Interventional magnetic resonance imaging-guided cell transplantation into the brain with radially branched deployment.

PubMed

Silvestrini, Matthew T; Yin, Dali; Martin, Alastair J; Coppes, Valerie G; Mann, Preeti; Larson, Paul S; Starr, Philip A; Zeng, Xianmin; Gupta, Nalin; Panter, S S; Desai, Tejal A; Lim, Daniel A

2015-01-01

Intracerebral cell transplantation is being pursued as a treatment for many neurological diseases, and effective cell delivery is critical for clinical success. To facilitate intracerebral cell transplantation at the scale and complexity of the human brain, we developed a platform technology that enables radially branched deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. iMRI-guided RBD functioned as an "add-on" to standard neurosurgical and imaging workflows, and procedures were performed in a commonly available clinical MRI scanner. Multiple deposits of super paramagnetic iron oxide beads were safely delivered to the striatum of live swine, and distribution to the entire putamen was achieved via a single cannula insertion in human cadaveric heads. Human embryonic stem cell-derived dopaminergic neurons were biocompatible with the iMRI-guided RBD platform and successfully delivered with iMRI guidance into the swine striatum. Thus, iMRI-guided RBD overcomes some of the technical limitations inherent to the use of straight cannulas and standard stereotactic targeting. This platform technology could have a major impact on the clinical translation of a wide range of cell therapeutics for the treatment of many neurological diseases.

Genetically encoded reporters for hyperpolarized xenon magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Shapiro, Mikhail G.; Ramirez, R. Matthew; Sperling, Lindsay J.; Sun, George; Sun, Jinny; Pines, Alexander; Schaffer, David V.; Bajaj, Vikram S.

2014-07-01

Magnetic resonance imaging (MRI) enables high-resolution non-invasive observation of the anatomy and function of intact organisms. However, previous MRI reporters of key biological processes tied to gene expression have been limited by the inherently low molecular sensitivity of conventional 1H MRI. This limitation could be overcome through the use of hyperpolarized nuclei, such as in the noble gas xenon, but previous reporters acting on such nuclei have been synthetic. Here, we introduce the first genetically encoded reporters for hyperpolarized 129Xe MRI. These expressible reporters are based on gas vesicles (GVs), gas-binding protein nanostructures expressed by certain buoyant microorganisms. We show that GVs are capable of chemical exchange saturation transfer interactions with xenon, which enables chemically amplified GV detection at picomolar concentrations (a 100- to 10,000-fold improvement over comparable constructs for 1H MRI). We demonstrate the use of GVs as heterologously expressed indicators of gene expression and chemically targeted exogenous labels in MRI experiments performed on living cells.

Tracking the Evolution of Cerebral Gadolinium-Enhancing Lesions to Persistent T1 Black Holes in Multiple Sclerosis: Validation of a Semiautomated Pipeline.

PubMed

Andermatt, Simon; Papadopoulou, Athina; Radue, Ernst-Wilhelm; Sprenger, Till; Cattin, Philippe

2017-09-01

Some gadolinium-enhancing multiple sclerosis (MS) lesions remain T1-hypointense over months ("persistent black holes, BHs") and represent areas of pronounced tissue loss. A reduced conversion of enhancing lesions to persistent BHs could suggest a favorable effect of a medication on tissue repair. However, the individual tracking of enhancing lesions can be very time-consuming in large clinical trials. We created a semiautomated workflow for tracking the evolution of individual MS lesions, to calculate the proportion of enhancing lesions becoming persistent BHs at follow-up. Our workflow automatically coregisters, compares, and detects overlaps between lesion masks at different time points. We tested the algorithm in a data set of Magnetic Resonance images (1.5 and 3T; spin-echo T1-sequences) from a phase 3 clinical trial (n = 1,272), in which all enhancing lesions and all BHs had been previously segmented at baseline and year 2. The algorithm analyzed the segmentation masks in a longitudinal fashion to determine which enhancing lesions at baseline turned into BHs at year 2. Images of 50 patients (192 enhancing lesions) were also reviewed by an experienced MRI rater, blinded to the algorithm results. In this MRI data set, there were no cases that could not be processed by the algorithm. At year 2, 417 lesions were classified as persistent BHs (417/1,613 = 25.9%). The agreement between the rater and the algorithm was > 98%. Due to the semiautomated procedure, this algorithm can be of great value in the analysis of large clinical trials, when a rater-based analysis would be time-consuming. Copyright © 2017 by the American Society of Neuroimaging.

The Tracking Resonance Frequency Method for Photoacoustic Measurements Based on the Phase Response

NASA Astrophysics Data System (ADS)

Suchenek, Mariusz

2017-04-01

One of the major issues in the use of the resonant photoacoustic cell is the resonance frequency of the cell. The frequency is not stable, and its changes depend mostly on temperature and gas mixture. This paper presents a new method for tracking resonance frequency, where both the amplitude and phase are calculated from the input samples. The stimulating frequency can be adjusted to the resonance frequency of the cell based on the phase. This method was implemented using a digital measurement system with an analog to digital converter, field programmable gate array (FPGA) and a microcontroller. The resonance frequency was changed by the injection of carbon dioxide into the cell. A theoretical description and experimental results are also presented.

Tissue Tracking: Applications for Brain MRI Classification

DTIC Science & Technology

2007-01-01

General Hospital, Center for Morphometric Analysis.10,11 The IBSR data-sets are T1-weighted, 3D coronal brain scans after having been positionally...learned priors,” Image Processing, IEEE Transactions on 9(2), pp. 299–301, 2000. 5. P. Olver, G. Sapiro, and A. Tannenbaum, “Invariant Geometric Evolutions...MRI,” NeuroImage 22(3), pp. 1060–1075, 2004. 16. A. Zijdenbos, B. Dawant, R. Margolin, and A. Palmer, “ Morphometric analysis of white matter lesions in

A Cinematic Magnetic Resonance Imaging Study of Milk of Magnesia Laxative and an Antiflatulent Diet to Reduce Intrafraction Prostate Motion

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

Nichol, Alan M.; Warde, Padraig R.; Lockwood, Gina A.

Purpose: To determine the reduction of prostate motion during a typical radiotherapy (RT) fraction from a bowel regimen comprising an antiflatulent diet and daily milk of magnesia. Methods and Materials: Forty-two patients with T1c-T2c prostate cancer voided the bladder and rectum before three cinematic magnetic resonance imaging scans obtained every 9 s for 9 min in a vacuum immobilization device. The MRIs were at baseline without bowel regimen (MRI-BL), before CT planning with bowel regimen (MRI-CT), and before a randomly assigned RT fraction (1-42) with bowel regimen (MRI-RT). A single observer tracked displacement of the posterior midpoint (PM) of themore » prostate. The primary endpoints were comparisons of the proportion of time that the PM was displaced >3 mm (PTPM3) from its initial position, and the secondary endpoints were comparisons of the reduction of initial rectal area, with and without the bowel regimen. Results: The mean rectal area was: 13.5 cm{sup 2} at MRI-BL, 12.7 cm{sup 2} at MRI-CT, and 12.3 cm{sup 2} at MRI-RT (MRI-BL vs. MRI-CT, p = 0.11; MRI-BL vs. MRI-CT, p = 0.07). Moving rectal gas alone (56%) and moving gas and stool (18%) caused 74% of intrafraction prostate motion. The PTPM3 was 11.3% at MRI-BL, 4.8% at MRI-CT, and 12.0% at MRI-RT (MRI-BL vs. MRI-CT, p = 0.12; MRI-BL vs. MRI-RT, p = 0.89). Conclusion: For subjects voiding their rectum before imaging, an antiflatulent diet and milk of magnesia laxative did not significantly reduce initial rectal area or intrafraction prostate motion.« less

Real-time MRI-guided needle intervention for cryoablation: a phantom study

NASA Astrophysics Data System (ADS)

Gao, Wenpeng; Jiang, Baichuan; Kacher, Dan F.; Fetics, Barry; Nevo, Erez; Lee, Thomas C.; Jayender, Jagadeesan

2017-03-01

MRI-guided needle intervention for cryoablation is a promising way to relieve the pain and treat the cancer. However, the limited size of MRI bore makes it impossible for clinicians to perform the operation in the bore. The patients had to be moved into the bore for scanning to verify the position of the needle's tip and out for adjusting the needle's trajectory. Real-time needle tracking and shown in MR images is of importance for clinicians to perform the operation more efficiently. In this paper, we have instrumented the cryotherapy needle with a MRI-safe electromagnetic (EM) sensor and optical sensor to measure the needle's position and orientation. To overcome the limitation of line-of-sight for optical sensor and the poor dynamic performance of the EM sensor, Kalman filter based data fusion is developed. Further, we developed a navigation system in open-source software, 3D Slicer, to provide accurate visualization of the needle and the surrounding anatomy. Experiment of simulation the needle intervention at the entrance was performed with a realistic spine phantom to quantify the accuracy of the navigation using the retrospective analysis method. Eleven trials of needle insertion were performed independently. The target accuracy with the navigation using only EM sensor, only optical sensor and data fusion are 2.27 +/-1.60 mm, 4.11 +/- 1.77 mm and 1.91 - 1.10 mm, respectively.

Prolonged Dye Release from Mesoporous Silica-Based Imaging Probes Facilitates Long-Term Optical Tracking of Cell Populations In Vivo.

PubMed

Rosenholm, Jessica M; Gulin-Sarfraz, Tina; Mamaeva, Veronika; Niemi, Rasmus; Özliseli, Ezgi; Desai, Diti; Antfolk, Daniel; von Haartman, Eva; Lindberg, Desiré; Prabhakar, Neeraj; Näreoja, Tuomas; Sahlgren, Cecilia

2016-03-23

Nanomedicine is gaining ground worldwide in therapy and diagnostics. Novel nanoscopic imaging probes serve as imaging tools for studying dynamic biological processes in vitro and in vivo. To allow detectability in the physiological environment, the nanostructure-based probes need to be either inherently detectable by biomedical imaging techniques, or serve as carriers for existing imaging agents. In this study, the potential of mesoporous silica nanoparticles carrying commercially available fluorochromes as self-regenerating cell labels for long-term cellular tracking is investigated. The particle surface is organically modified for enhanced cellular uptake, the fluorescence intensity of labeled cells is followed over time both in vitro and in vivo. The particles are not exocytosed and particles which escaped cells due to cell injury or death are degraded and no labeling of nontargeted cell populations are observed. The labeling efficiency is significantly improved as compared to that of quantum dots of similar emission wavelength. Labeled human breast cancer cells are xenotransplanted in nude mice, and the fluorescent cells can be detected in vivo for a period of 1 month. Moreover, ex vivo analysis reveals fluorescently labeled metastatic colonies in lymph node and rib, highlighting the capability of the developed probes for tracking of metastasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neural mechanisms of eye contact when listening to another person talking

PubMed Central

Borowiak, Kamila; Tudge, Luke; Otto, Carolin; von Kriegstein, Katharina

2017-01-01

Abstract Eye contact occurs frequently and voluntarily during face-to-face verbal communication. However, the neural mechanisms underlying eye contact when it is accompanied by spoken language remain unexplored to date. Here we used a novel approach, fixation-based event-related functional magnetic resonance imaging (fMRI), to simulate the listener making eye contact with a speaker during verbal communication. Participants’ eye movements and fMRI data were recorded simultaneously while they were freely viewing a pre-recorded speaker talking. The eye tracking data were then used to define events for the fMRI analyses. The results showed that eye contact in contrast to mouth fixation involved visual cortical areas (cuneus, calcarine sulcus), brain regions related to theory of mind/intentionality processing (temporoparietal junction, posterior superior temporal sulcus, medial prefrontal cortex) and the dorsolateral prefrontal cortex. In addition, increased effective connectivity was found between these regions for eye contact in contrast to mouth fixations. The results provide first evidence for neural mechanisms underlying eye contact when watching and listening to another person talking. The network we found might be well suited for processing the intentions of communication partners during eye contact in verbal communication. PMID:27576745

Technologies enabling autologous neural stem cell-based therapies for neurodegenerative disease and injury

NASA Astrophysics Data System (ADS)

Bakhru, Sasha H.

The intrinsic abilities of mammalian neural stem cells (NSCs) to self-renew, migrate over large distances, and give rise to all primary neural cell types of the brain offer unprecedented opportunity for cell-based treatment of neurodegenerative diseases and injuries. This thesis discusses development of technologies in support of autologous NSC-based therapies, encompassing harvest of brain tissue biopsies from living human patients; isolation of NSCs from harvested tissue; efficient culture and expansion of NSCs in 3D polymeric microcapsule culture systems; optimization of microcapsules as carriers for efficient in vivo delivery of NSCs; genetic engineering of NSCs for drug-induced, enzymatic release of transplanted NSCs from microcapsules; genetic engineering for drug-induced differentiation of NSCs into specific therapeutic cell types; and synthesis of chitosan/iron-oxide nanoparticles for labeling of NSCs and in vivo tracking by cellular MRI. Sub-millimeter scale tissue samples were harvested endoscopically from subventricular zone regions of living patient brains, secondary to neurosurgical procedures including endoscopic third ventriculostomy and ventriculoperitoneal shunt placement. On average, 12,000 +/- 3,000 NSCs were isolated per mm 3 of subventricular zone tissue, successfully demonstrated in 26 of 28 patients, ranging in age from one month to 68 years. In order to achieve efficient expansion of isolated NSCs to clinically relevant numbers (e.g. hundreds of thousands of cells in Parkinson's disease and tens of millions of cells in multiple sclerosis), an extracellular matrix-inspired, microcapsule-based culture platform was developed. Initial culture experiments with murine NSCs yielded unprecedented expansion folds of 30x in 5 days, from initially minute NSC populations (154 +/- 15 NSCs per 450 mum diameter capsule). Within 7 days, NSCs expanded as almost perfectly homogenous populations, with 94.9% +/- 4.1% of cultured cells staining positive for Nestin, a marker for NSCs, 81.4 +/- 3.7% of cells staining positive for KI67, a proliferation marker, and 0% of cultured cells staining positive for GFAP, a marker indicative of undesired astrocytes. The same microcapsules used for expansion were designed to contain NSCs beyond delivery to the brain, maintaining NSC phenotype and suppressing undesired astroglial differentiation during the acute phase of inflammation beyond surgical implantation. In vitro, >80% of encapsulated cells challenged with 0.1 % fetal calf serum over five days in culture showed persistent Nestin expression, compared to <20% under the same conditions outside of microcapsules, indicating that the microcapsule interior can preserve phenotype in the presence of serum concentrations at least an order of magnitude greater than those estimated to be present in cerebrospinal fluid (CSF) after surgical implantation. In order to release transplanted NSCs on cue from microcapsules after the acute inflammatory response, NSCs were genetically engineered using the Tet-onRTM drug-inducible gene expression system to produce and secrete the enzyme alginase in response to the inducer drug doxycycline. Engineered NSCs, exposed to 1 mug/ml doxycycline, produced sufficient alginase to digest alginate, a structural component of the microcapsule wall, within 8 hours, effectively dissolving microcapsules and releasing encapsulated NSCs. In order to direct differentiation of transplanted NSCs towards therapeutically valuable cell types (e.g. dopaminergic neurons in case of Parkinson's disease and oligodendrocytes in case of multiple sclerosis), NSCs were genetically engineered to inducibly express the proneural transcription factors NGN1 and Olig1 on demand. Induced expression of NGN1 yielded >90% neurons, induced expression of Olig1 yielded >80% oligodendrocytes, compared to neuron/oligodendrocyte yields <10% for GFP-expressing controls. NSCs with the capacity to inducibly express these transcription factors showed preservation of therapeutically valuable migratory capacity (average RMS migration rate of approximately 40 mum/hr before induction). Differentiating NSCs, however, showed largely arrested migration within 12 hours of induction for Olig1 cells and 36 hours of induction for NGN1 cells. Finally, tracking of NSCs at the single cell level via high-resolution (11.7 T) cellular MRI, was made possible through development of contrast-enhancing, chitosan-functionalized ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles that are rapidly uptaken by NSCs. Chitosan, a positively charged derivative of chitin, promotes electrostatically-driven attachment of chitosan-USPIO nanoparticles to negatively charged domains on the outer leaflet of the cellular membrane, enhancing uptake by clathrin-mediated endocytosis (>10x increase in uptake efficiency relative to unmodified USPIO). Uptaken USPIOs remained in cells for at least 8 days due to charge-induced endosomal escape of nanoparticles into the cytosol. In combination, all developed technologies offer a basis for clinical evaluation of autologous neural stem cell replacement therapies, the future of which promises to shift the present paradigm for treatment of neurodegenerative diseases and injuries.

Extracting Fluorescent Reporter Time Courses of Cell Lineages from High-Throughput Microscopy at Low Temporal Resolution

PubMed Central

Downey, Mike J.; Jeziorska, Danuta M.; Ott, Sascha; Tamai, T. Katherine; Koentges, Georgy; Vance, Keith W.; Bretschneider, Till

2011-01-01

The extraction of fluorescence time course data is a major bottleneck in high-throughput live-cell microscopy. Here we present an extendible framework based on the open-source image analysis software ImageJ, which aims in particular at analyzing the expression of fluorescent reporters through cell divisions. The ability to track individual cell lineages is essential for the analysis of gene regulatory factors involved in the control of cell fate and identity decisions. In our approach, cell nuclei are identified using Hoechst, and a characteristic drop in Hoechst fluorescence helps to detect dividing cells. We first compare the efficiency and accuracy of different segmentation methods and then present a statistical scoring algorithm for cell tracking, which draws on the combination of various features, such as nuclear intensity, area or shape, and importantly, dynamic changes thereof. Principal component analysis is used to determine the most significant features, and a global parameter search is performed to determine the weighting of individual features. Our algorithm has been optimized to cope with large cell movements, and we were able to semi-automatically extract cell trajectories across three cell generations. Based on the MTrackJ plugin for ImageJ, we have developed tools to efficiently validate tracks and manually correct them by connecting broken trajectories and reassigning falsely connected cell positions. A gold standard consisting of two time-series with 15,000 validated positions will be released as a valuable resource for benchmarking. We demonstrate how our method can be applied to analyze fluorescence distributions generated from mouse stem cells transfected with reporter constructs containing transcriptional control elements of the Msx1 gene, a regulator of pluripotency, in mother and daughter cells. Furthermore, we show by tracking zebrafish PAC2 cells expressing FUCCI cell cycle markers, our framework can be easily adapted to different cell types and fluorescent markers. PMID:22194797

Occurrence of lower cloud albedo in ship tracks

NASA Astrophysics Data System (ADS)

Chen, Y.-C.; Christensen, M. W.; Xue, L.; Sorooshian, A.; Stephens, G. L.; Rasmussen, R. M.; Seinfeld, J. H.

2012-09-01

The concept of geoengineering by marine cloud brightening is based on seeding marine stratocumulus clouds with sub-micrometer sea-salt particles to enhance the cloud droplet number concentration and cloud albedo, thereby producing a climate cooling effect. The efficacy of this as a strategy for global cooling rests on the extent to which aerosol-perturbed marine clouds will respond with increased albedo. Ship tracks, quasi-linear cloud features prevalent in oceanic regions impacted by ship exhaust, are a well-known manifestation of the effect of aerosol injection on marine clouds. We present here an analysis of the albedo responses in ship tracks, based on in situ aircraft measurements and three years of satellite observations of 589 individual ship tracks. It is found that the sign (increase or decrease) and magnitude of the albedo response in ship tracks depends on the mesoscale cloud structure, the free tropospheric humidity, and cloud top height. In a closed cell structure (cloud cells ringed by a perimeter of clear air), nearly 30% of ship tracks exhibited a decreased albedo. Detailed cloud responses must be accounted for in global studies of the potential efficacy of sea-spray geoengineering as a means to counteract global warming.

Tracking flow of leukocytes in blood for drug analysis

NASA Astrophysics Data System (ADS)

Basharat, Arslan; Turner, Wesley; Stephens, Gillian; Badillo, Benjamin; Lumpkin, Rick; Andre, Patrick; Perera, Amitha

2011-03-01

Modern microscopy techniques allow imaging of circulating blood components under vascular flow conditions. The resulting video sequences provide unique insights into the behavior of blood cells within the vasculature and can be used as a method to monitor and quantitate the recruitment of inflammatory cells at sites of vascular injury/ inflammation and potentially serve as a pharmacodynamic biomarker, helping screen new therapies and individualize dose and combinations of drugs. However, manual analysis of these video sequences is intractable, requiring hours per 400 second video clip. In this paper, we present an automated technique to analyze the behavior and recruitment of human leukocytes in whole blood under physiological conditions of shear through a simple multi-channel fluorescence microscope in real-time. This technique detects and tracks the recruitment of leukocytes to a bioactive surface coated on a flow chamber. Rolling cells (cells which partially bind to the bioactive matrix) are detected counted, and have their velocity measured and graphed. The challenges here include: high cell density, appearance similarity, and low (1Hz) frame rate. Our approach performs frame differencing based motion segmentation, track initialization and online tracking of individual leukocytes.

A choline derivate-modified nanoprobe for glioma diagnosis using MRI

NASA Astrophysics Data System (ADS)

Li, Jianfeng; Huang, Shixian; Shao, Kun; Liu, Yang; An, Sai; Kuang, Yuyang; Guo, Yubo; Ma, Haojun; Wang, Xuxia; Jiang, Chen

2013-04-01

Gadolinium (Gd) chelate contrast-enhanced magnetic resonance imaging (MRI) is a preferred method of glioma detection and preoperative localisation because it offers high spatial resolution and non-invasive deep tissue penetration. Gd-based contrast agents, such as Gd-diethyltriaminepentaacetic acid (DTPA-Gd, Magnevist), are widely used clinically for tumor diagnosis. However, the Gd-based MRI approach is limited for patients with glioma who have an uncompromised blood-brain barrier (BBB). Moreover, the rapid renal clearance and non-specificity of such contrast agents further hinders their prevalence. We present a choline derivate (CD)-modified nanoprobe with BBB permeability, glioma specificity and a long blood half-life. Specific accumulation of the nanoprobe in gliomas and subsequent MRI contrast enhancement are demonstrated in vitro in U87 MG cells and in vivo in a xenograft nude model. BBB and glioma dual targeting by this nanoprobe may facilitate precise detection of gliomas with an uncompromised BBB and may offer better preoperative and intraoperative tumor localization.

Brain MRI fiber-tracking reveals white matter alterations in hypertensive patients without damage at conventional neuroimaging.

PubMed

Carnevale, Lorenzo; D'Angelosante, Valentina; Landolfi, Alessandro; Grillea, Giovanni; Selvetella, Giulio; Storto, Marianna; Lembo, Giuseppe; Carnevale, Daniela

2018-06-12

Hypertension is one of the main risk factor for dementia. The subtle damage provoked by chronic high blood pressure in the brain is usually evidenced by conventional magnetic resonance imaging (MRI), in terms of white matter (WM) hyperintensities or cerebral atrophy. However, it is clear that by the time brain damage is visible, it may be too late hampering neurodegeneration. Aim of this study was to characterize a signature of early brain damage induced by hypertension, before the neurodegenerative injury manifests. This work was conducted on hypertensive and normotensive subjects with no sign of structural damage at conventional neuroimaging and no diagnosis of dementia revealed by neuropsychological assessment. All individuals underwent cardiological clinical examination in order to define the hypertensive status and the related target organ damage. Additionally, patients were subjected to DTI-MRI scan to identify microstructural damage of WM by probabilistic fiber-tracking. To gain insights in the neurocognitive profile of patients a specific battery of tests was administered. As primary outcome of the study we aimed at finding any specific signature of fiber-tracts alterations in hypertensive patients, associated with an impairment of the related cognitive functions. Hypertensive patients showed significant alterations in three specific WM fiber-tracts: the anterior thalamic radiation, the superior longitudinal fasciculus and the forceps minor. Hypertensive patients also scored significantly worse in the cognitive domains ascribable to brain regions connected through those WM fiber-tracts, showing decreased performances in executive functions, processing speed, memory, and paired associative learning tasks. Overall, WM fiber-tracking on MRI evidenced an early signature of damage in hypertensive patients when otherwise undetectable by conventional neuroimaging. In perspective, this approach could allow identifying those patients that are in initial stages of brain damage and could benefit of therapies aimed at limiting the transition to dementia and neurodegeneration.

Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

1991-01-01

The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

Oxygen Nanobubble Tracking by Light Scattering in Single Cells and Tissues.

PubMed

Bhandari, Pushpak; Wang, Xiaolei; Irudayaraj, Joseph

2017-03-28

Oxygen nanobubbles (ONBs) have significant potential in targeted imaging and treatment in cancer diagnosis and therapy. Precise localization and tracking of single ONBs is demonstrated based on hyperspectral dark-field microscope (HSDFM) to image and track single oxygen nanobubbles in single cells. ONBs were proposed as promising contrast-generating imaging agents due to their strong light scattering generated from nonuniformity of refractive index at the interface. With this powerful platform, we have revealed the trajectories and quantities of ONBs in cells, and demonstrated the relation between the size and diffusion coefficient. We have also evaluated the presence of ONBs in the nucleus with respect to an increase in incubation time and have quantified the uptake in single cells in ex vivo tumor tissues. Our results demonstrate that HSDFM can be a versatile platform to detect and measure cellulosic nanoparticles at the single-cell level and to assess the dynamics and trajectories of this delivery system.

Reactive granular optics for passive tracking of the sun

NASA Astrophysics Data System (ADS)

Frenkel, I.; Niv, A.

2017-08-01

The growing need for cost-effective renewable energy sources is hampered by the stagnation in solar cell technology, thus preventing a substantial reduction in the module and energy-production price. Lowering the energy-production cost could be achieved by using modules with efficiency. One of the possible means for increasing the module efficiency is concentrated photovoltaics (CPV). CPV, however, requires complex and accurate active tracking of the sun that reduces much of its cost-effectiveness. Here, we propose a passive tracking scheme based on a reactive optical device. The optical reaction is achieved by a new kind of light activated mechanical force that acts on micron-sized particles. This optical force allows the formation of granular disordered optical media that can be switched from being opaque to become transparent based on the intensity of light it interacts with. Such media gives rise to an efficient passive tracking scheme that when combined with an external optical cavity forms a new solar power conversion approach. Being external to the cell itself, this approach is indifferent to the type of semiconducting material that is used, as well as to other aspects of the cell design. This, in turn, liberates the cell layout from its optical constraints thus paving the way to higher efficiencies at lower module price.

Magnetic particle imaging for in vivo blood flow velocity measurements in mice

NASA Astrophysics Data System (ADS)

Kaul, Michael G.; Salamon, Johannes; Knopp, Tobias; Ittrich, Harald; Adam, Gerhard; Weller, Horst; Jung, Caroline

2018-03-01

Magnetic particle imaging (MPI) is a new imaging technology. It is a potential candidate to be used for angiographic purposes, to study perfusion and cell migration. The aim of this work was to measure velocities of the flowing blood in the inferior vena cava of mice, using MPI, and to evaluate it in comparison with magnetic resonance imaging (MRI). A phantom mimicking the flow within the inferior vena cava with velocities of up to 21 cm s‑1 was used for the evaluation of the applied analysis techniques. Time–density and distance–density analyses for bolus tracking were performed to calculate flow velocities. These findings were compared with the calibrated velocities set by a flow pump, and it can be concluded that velocities of up to 21 cm s‑1 can be measured by MPI. A time–density analysis using an arrival time estimation algorithm showed the best agreement with the preset velocities. In vivo measurements were performed in healthy FVB mice (n  =  10). MRI experiments were performed using phase contrast (PC) for velocity mapping. For MPI measurements, a standardized injection of a superparamagnetic iron oxide tracer was applied. In vivo MPI data were evaluated by a time–density analysis and compared to PC MRI. A Bland–Altman analysis revealed good agreement between the in vivo velocities acquired by MRI of 4.0  ±  1.5 cm s‑1 and those measured by MPI of 4.8  ±  1.1 cm s‑1. Magnetic particle imaging is a new tool with which to measure and quantify flow velocities. It is fast, radiation-free, and produces 3D images. It therefore offers the potential for vascular imaging.

A special issue on reviews in biomedical applications of nanomaterials, tissue engineering, stem cells, bioimaging, and toxicity.

PubMed

Nalwa, Hari Singh

2014-10-01

This second special issue of the Journal of Biomedical Nanotechnology in a series contains another 30 state-of-the-art reviews focused on the biomedical applications of nanomaterials, biosensors, bone tissue engineering, MRI and bioimaging, single-cell detection, stem cells, endothelial progenitor cells, toxicity and biosafety of nanodrugs, nanoparticle-based new therapeutic approaches for cancer, hepatic and cardiovascular disease.

The Behavioral and Neural Mechanisms Underlying the Tracking of Expertise

PubMed Central

Boorman, Erie D.; O’Doherty, John P.; Adolphs, Ralph; Rangel, Antonio

2013-01-01

Summary Evaluating the abilities of others is fundamental for successful economic and social behavior. We investigated the computational and neurobiological basis of ability tracking by designing an fMRI task that required participants to use and update estimates of both people and algorithms’ expertise through observation of their predictions. Behaviorally, we find a model-based algorithm characterized subject predictions better than several alternative models. Notably, when the agent’s prediction was concordant rather than discordant with the subject’s own likely prediction, participants credited people more than algorithms for correct predictions and penalized them less for incorrect predictions. Neurally, many components of the mentalizing network—medial prefrontal cortex, anterior cingulate gyrus, temporoparietal junction, and precuneus—represented or updated expertise beliefs about both people and algorithms. Moreover, activity in lateral orbitofrontal and medial prefrontal cortex reflected behavioral differences in learning about people and algorithms. These findings provide basic insights into the neural basis of social learning. PMID:24360551

89Zr-Oxine Complex for In Vivo PET Imaging of Labelled Cells and Associated Methods | NCI Technology Transfer Center | TTC

Cancer.gov

The National Cancer Institute seek parties interested in in-licensing and/or collaborative research to develop and commercialize cell labeling, cell tracking, cell trafficking, cell-based therapy, and PET imaging for cancer.

Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System.

PubMed

Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Masarudin, Mas Jaffri; Ahmad Saad, Fathinul Fikri

2017-08-31

We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO₃)₃ as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment.

A detailed study of gold-nanoparticle loaded cells using X-ray based techniques for cell-tracking applications with single-cell sensitivity

NASA Astrophysics Data System (ADS)

Astolfo, Alberto; Arfelli, Fulvia; Schültke, Elisabeth; James, Simon; Mancini, Lucia; Menk, Ralf-Hendrik

2013-03-01

In the present study complementary high-resolution imaging techniques on different length scales are applied to elucidate a cellular loading protocol of gold nanoparticles and subsequently its impact on long term and high-resolution cell-tracking utilizing X-ray technology. Although demonstrated for malignant cell lines the results can be applied to non-malignant cell lines as well. In particular the accumulation of the gold marker per cell has been assessed quantitatively by virtue of electron microscopy, two-dimensional X-ray fluorescence imaging techniques and X-ray CT with micrometric and sub-micrometric resolution. Moreover, utilizing these techniques the three dimensional distribution of the incorporated nanoparticles, which are sequestered in lysosomes as a permanent marker, could be determined. The latter allowed elucidation of the gold partition during mitosis and the cell size, which subsequently enabled us to define the optimal instrument settings of a compact microCT system to visualize gold loaded cells. The results obtained demonstrate the feasibility of cell-tracking using X-ray CT with compact sources.

Intelligent Paging Based Mobile User Tracking Using Fuzzy Logic

NASA Astrophysics Data System (ADS)

Saha, Sajal; Dutta, Raju; Debnath, Soumen; Mukhopadhyay, Asish K.

2010-11-01

In general, a mobile user travels in a predefined path that depends mostly on the user's characteristics. Thus, tracking the locations of a mobile user is one of the challenges for location management. In this paper, we introduce a movement pattern learning strategy system to track the user's movements using adaptive fuzzy logic. Our fuzzy inference system extracts patterns from the historical data record of the cell numbers along with the date and time stamp of the users occupying the cell. Implementation of this strategy has been evaluated with the real time user data which proves the efficiency and accuracy of the model. This mechanism not only reduces user location tracking costs, but also significantly decreases the call-loss rates and average paging delays.

Representation of limb kinematics in Purkinje cell simple spike discharge is conserved across multiple tasks

PubMed Central

Hewitt, Angela L.; Popa, Laurentiu S.; Pasalar, Siavash; Hendrix, Claudia M.

2011-01-01

Encoding of movement kinematics in Purkinje cell simple spike discharge has important implications for hypotheses of cerebellar cortical function. Several outstanding questions remain regarding representation of these kinematic signals. It is uncertain whether kinematic encoding occurs in unpredictable, feedback-dependent tasks or kinematic signals are conserved across tasks. Additionally, there is a need to understand the signals encoded in the instantaneous discharge of single cells without averaging across trials or time. To address these questions, this study recorded Purkinje cell firing in monkeys trained to perform a manual random tracking task in addition to circular tracking and center-out reach. Random tracking provides for extensive coverage of kinematic workspaces. Direction and speed errors are significantly greater during random than circular tracking. Cross-correlation analyses comparing hand and target velocity profiles show that hand velocity lags target velocity during random tracking. Correlations between simple spike firing from 120 Purkinje cells and hand position, velocity, and speed were evaluated with linear regression models including a time constant, τ, as a measure of the firing lead/lag relative to the kinematic parameters. Across the population, velocity accounts for the majority of simple spike firing variability (63 ± 30% of Radj2), followed by position (28 ± 24% of Radj2) and speed (11 ± 19% of Radj2). Simple spike firing often leads hand kinematics. Comparison of regression models based on averaged vs. nonaveraged firing and kinematics reveals lower Radj2 values for nonaveraged data; however, regression coefficients and τ values are highly similar. Finally, for most cells, model coefficients generated from random tracking accurately estimate simple spike firing in either circular tracking or center-out reach. These findings imply that the cerebellum controls movement kinematics, consistent with a forward internal model that predicts upcoming limb kinematics. PMID:21795616

Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent.

PubMed

Santra, Santimukul; Jativa, Samuel D; Kaittanis, Charalambos; Normand, Guillaume; Grimm, Jan; Perez, J Manuel

2012-08-28

Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the poly(acrylic acid) (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA), yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T(1)). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T(1) relaxation rate (1/T(1)) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T(1)-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T(1) signal was observed. This result suggests that, upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T(1) activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T(1) activation of the probe coincided with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T(1) nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI.

A software solution for recording circadian oscillator features in time-lapse live cell microscopy.

PubMed

Sage, Daniel; Unser, Michael; Salmon, Patrick; Dibner, Charna

2010-07-06

Fluorescent and bioluminescent time-lapse microscopy approaches have been successfully used to investigate molecular mechanisms underlying the mammalian circadian oscillator at the single cell level. However, most of the available software and common methods based on intensity-threshold segmentation and frame-to-frame tracking are not applicable in these experiments. This is due to cell movement and dramatic changes in the fluorescent/bioluminescent reporter protein during the circadian cycle, with the lowest expression level very close to the background intensity. At present, the standard approach to analyze data sets obtained from time lapse microscopy is either manual tracking or application of generic image-processing software/dedicated tracking software. To our knowledge, these existing software solutions for manual and automatic tracking have strong limitations in tracking individual cells if their plane shifts. In an attempt to improve existing methodology of time-lapse tracking of a large number of moving cells, we have developed a semi-automatic software package. It extracts the trajectory of the cells by tracking theirs displacements, makes the delineation of cell nucleus or whole cell, and finally yields measurements of various features, like reporter protein expression level or cell displacement. As an example, we present here single cell circadian pattern and motility analysis of NIH3T3 mouse fibroblasts expressing a fluorescent circadian reporter protein. Using Circadian Gene Express plugin, we performed fast and nonbiased analysis of large fluorescent time lapse microscopy datasets. Our software solution, Circadian Gene Express (CGE), is easy to use and allows precise and semi-automatic tracking of moving cells over longer period of time. In spite of significant circadian variations in protein expression with extremely low expression levels at the valley phase, CGE allows accurate and efficient recording of large number of cell parameters, including level of reporter protein expression, velocity, direction of movement, and others. CGE proves to be useful for the analysis of widefield fluorescent microscopy datasets, as well as for bioluminescence imaging. Moreover, it might be easily adaptable for confocal image analysis by manually choosing one of the focal planes of each z-stack of the various time points of a time series. CGE is a Java plugin for ImageJ; it is freely available at: http://bigwww.epfl.ch/sage/soft/circadian/.

Utility of MRI versus tumor markers for post-treatment surveillance of marker-positive CNS germ cell tumors.

PubMed

Cheung, Victoria; Segal, Devorah; Gardner, Sharon L; Zagzag, David; Wisoff, Jeffrey H; Allen, Jeffrey C; Karajannis, Matthias A

2016-09-01

Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.

The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI.

PubMed

Plow, Ela B; Cattaneo, Zaira; Carlson, Thomas A; Alvarez, George A; Pascual-Leone, Alvaro; Battelli, Lorella

2014-01-01

A balance of mutual tonic inhibition between bi-hemispheric posterior parietal cortices is believed to play an important role in bilateral visual attention. However, experimental support for this notion has been mainly drawn from clinical models of unilateral damage. We have previously shown that low-frequency repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a contralateral attentional deficit in bilateral visual tracking. Here, we used functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily disrupts the inter-hemispheric balance between bilateral IPS in visual attention. Following application of 1 Hz rTMS over the left IPS, subjects performed a bilateral visual tracking task while their brain activity was recorded using fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS. Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL), lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL), Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal areas (MT+), showed higher activity. The brain activity of the homologues of these regions in the un-stimulated, right hemisphere was reversed. Interestingly, the evolution of network-wide activation related to attentional behavior following rTMS showed that activation of most occipital synergists adaptively compensated for contralateral and ipsilateral decrement after rTMS, while activation of parietal synergists, and SoG remained competing. This pattern of ipsilateral and contralateral activations empirically supports the hypothesized loss of inter-hemispheric balance that underlies clinical manifestation of visual attentional extinction.

Targeting Accuracy, Procedure Times and User Experience of 240 Experimental MRI Biopsies Guided by a Clinical Add-On Navigation System.

PubMed

Busse, Harald; Riedel, Tim; Garnov, Nikita; Thörmer, Gregor; Kahn, Thomas; Moche, Michael

2015-01-01

MRI is of great clinical utility for the guidance of special diagnostic and therapeutic interventions. The majority of such procedures are performed iteratively ("in-and-out") in standard, closed-bore MRI systems with control imaging inside the bore and needle adjustments outside the bore. The fundamental limitations of such an approach have led to the development of various assistance techniques, from simple guidance tools to advanced navigation systems. The purpose of this work was to thoroughly assess the targeting accuracy, workflow and usability of a clinical add-on navigation solution on 240 simulated biopsies by different medical operators. Navigation relied on a virtual 3D MRI scene with real-time overlay of the optically tracked biopsy needle. Smart reference markers on a freely adjustable arm ensured proper registration. Twenty-four operators - attending (AR) and resident radiologists (RR) as well as medical students (MS) - performed well-controlled biopsies of 10 embedded model targets (mean diameter: 8.5 mm, insertion depths: 17-76 mm). Targeting accuracy, procedure times and 13 Likert scores on system performance were determined (strong agreement: 5.0). Differences in diagnostic success rates (AR: 93%, RR: 88%, MS: 81%) were not significant. In contrast, between-group differences in biopsy times (AR: 4:15, RR: 4:40, MS: 5:06 min:sec) differed significantly (p<0.01). Mean overall rating was 4.2. The average operator would use the system again (4.8) and stated that the outcome justifies the extra effort (4.4). Lowest agreement was reported for the robustness against external perturbations (2.8). The described combination of optical tracking technology with an automatic MRI registration appears to be sufficiently accurate for instrument guidance in a standard (closed-bore) MRI environment. High targeting accuracy and usability was demonstrated on a relatively large number of procedures and operators. Between groups with different expertise there were significant differences in experimental procedure times but not in the number of successful biopsies.

SU-G-IeP4-11: Monitoring Tumor Growth in Subcutaneous Murine Tumor Model in Vivo: A Comparison Between MRI and Small Animal CT

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

Wang, B; He, W; Cvetkovic, D

Purpose: The purpose of the study is to compare the volume measurement of subcutaneous tumors in mice with different imaging platforms, namely a GE MRI and a Sofie-Biosciences small animal CT scanner. Methods: A549 human lung carcinoma cells and FaDu human head and neck squamous cell carcinoma cells were implanted subcutaneously into flanks of nude mice. Three FaDu tumors and three A549 tumors were included in this study. The MRI scans were done with a GE Signa 1.5 Tesla MR scanner using a fast T2-weighted sequence (70mm FOV and 1.2mm slice thickness), while the CT scans were done with themore » CT scanner on a Sofie-Biosciences G8 PET/CT platform dedicated for small animal studies (48mm FOV and 0.2mm slice thickness). Imaging contrast agent was not used in this study. Based on the DICOM images from MRI and CT scans, the tumors were contoured with Philips DICOM Viewer and the tumor volumes were obtained by summing up the contoured area and multiplied by the slice thickness. Results: The volume measurements based on the CT scans agree reasonably with that obtained with MR images for the subcutaneous tumors. The mean difference in the absolute tumor volumes between MRI- and CT-based measurements was found to be −6.2% ± 1.0%, with the difference defined as (VMR – VCT)*100%/VMR. Furthermore, we evaluated the normalized tumor volumes, which were defined for each tumor as V/V{sub 0} where V{sub 0} stands for the volume from the first MR or CT scan. The mean difference in the normalized tumor volumes was found to be 0.10% ± 0.96%. Conclusion: Despite the fact that the difference between normal and abnormal tissues is often less clear on small animal CT images than on MR images, one can still obtain reasonable tumor volume information with the small animal CT scans for subcutaneous murine xenograft models.« less

Complex Versus Simple Ankle Movement Training in Stroke Using Telerehabilitation: A Randomized Controlled Trial

PubMed Central

Deng, Huiqiong; Durfee, William K.; Nuckley, David J.; Rheude, Brandon S.; Severson, Amy E.; Skluzacek, Katie M.; Spindler, Kristen K.; Davey, Cynthia S.

2012-01-01

Background Telerehabilitation allows rehabilitative training to continue remotely after discharge from acute care and can include complex tasks known to create rich conditions for neural change. Objectives The purposes of this study were: (1) to explore the feasibility of using telerehabilitation to improve ankle dorsiflexion during the swing phase of gait in people with stroke and (2) to compare complex versus simple movements of the ankle in promoting behavioral change and brain reorganization. Design This study was a pilot randomized controlled trial. Setting Training was done in the participant's home. Testing was done in separate research labs involving functional magnetic resonance imaging (fMRI) and multi-camera gait analysis. Patients Sixteen participants with chronic stroke and impaired ankle dorsiflexion were assigned randomly to receive 4 weeks of telerehabilitation of the paretic ankle. Intervention Participants received either computerized complex movement training (track group) or simple movement training (move group). Measurements Behavioral changes were measured with the 10-m walk test and gait analysis using a motion capture system. Brain reorganization was measured with ankle tracking during fMRI. Results Dorsiflexion during gait was significantly larger in the track group compared with the move group. For fMRI, although the volume, percent volume, and intensity of cortical activation failed to show significant changes, the frequency count of the number of participants showing an increase versus a decrease in these values from pretest to posttest measurements was significantly different between the 2 groups, with the track group decreasing and the move group increasing. Limitations Limitations of this study were that no follow-up test was conducted and that a small sample size was used. Conclusions The results suggest that telerehabilitation, emphasizing complex task training with the paretic limb, is feasible and can be effective in promoting further dorsiflexion in people with chronic stroke. PMID:22095209