Targeting of Endothelin Receptors for Molecular Imaging of Atherosclerosis in Rabbits

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. Mar, 2002  |  Pubmed ID: 11884501

We wanted to determine whether a previously described in vivo accumulation of a (99m)Tc-labeled endothelin derivative in atherosclerotic lesions is mediated by binding to endothelin receptors. Furthermore, the expression of endothelin receptors in atherosclerotic lesions of 2 different rabbit animal models for atherosclerosis was to be evaluated to determine whether endothelin receptors generally are a suitable target for atherosclerosis imaging.

USPIO-enhanced Direct Thrombus MRI

Academic Radiology. Aug, 2002  |  Pubmed ID: 12188268

[Automatic Slice Tracking in Interventional Magnetic Resonance Imaging]

Zeitschrift Für Medizinische Physik. 2003  |  Pubmed ID: 14562540

Magnetic resonance imaging (MRI) is ideally suited to monitor minimally invasive operations with catheters or needles, since it offers both a superior soft-tissue contrast and the possibility to perform functional tests. In the present study, small radio-frequency coils were attached to the instruments in order to localize the MR-invisible instruments. The implementation of active instrument tracking is described on the basis of the example of active catheter tracking. In this case, the current position information of the instrument is used to automatically position the MRI slice at the catheter location. In combination with a user interface, the interventional radiologist is offered the possibility to perform vascular interventions from within the MR scanner room. At image update rates of approximately 3 Hz, tracking and placement of catheters in vascular structures are possible with interactive switching of slice orientation and image contrast. In an animal model, the technique was successfully used to selectively visualize the abdominal vessels and their branches under MRI guidance.

MR-guided Intravascular Procedures: Real-time Parameter Control and Automated Slice Positioning with Active Tracking Coils

Journal of Magnetic Resonance Imaging : JMRI. May, 2004  |  Pubmed ID: 15112307

To implement and optimize a real-time pulse sequence and user interface to perform intravascular interventions using active catheter tracking.

Dynamic Contrast-enhanced Magnetic Resonance Imaging Rapidly Indicates Vessel Regression in Human Squamous Cell Carcinomas Grown in Nude Mice Caused by VEGF Receptor 2 Blockade with DC101

Neoplasia (New York, N.Y.). May-Jun, 2004  |  Pubmed ID: 15153333

The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31). Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02). In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/- 843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/- 93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.

Simple Models Improve the Discrimination of Prostate Cancers from the Peripheral Gland by T1-weighted Dynamic MRI

European Radiology. Oct, 2004  |  Pubmed ID: 15232714

Evaluation of the accuracy of descriptive and physiological parameters calculated from signal intensity-time curves using T1-weighted dynamic contrast enhanced MRI (DCE MRI) to differentiate prostate cancers from the peripheral gland. Twenty-seven patients with prostate cancers were examined with DCE MRI prior radical prostatectomy. Regions of interest were defined in tumors and non-affected areas in the peripheral zone. Dynamic data were parameterized in amplitude and exchange rate constant (kep) using a two-compartment model. Additionally, relative slope during 26, 39, 52 and 65 s, areas under the curve (AUC) and time to start of signal intensity increase (tlag) were determined. Vessel density (VD) of excised prostates was quantified in tumor areas using a CD34 stain. The parameter slope52 showed 20% higher values (P<0.001) in tumors than in the peripheral gland and compared with the other parameters the largest area under the ROC curve (0.81). The minimum total error rate was attained at a cut-point of 0.021, yielding a sample value of sensitivity and specificity of 70% and 88%, respectively, and a bias-corrected sum of sensitivity and specificity of 1.54. In addition, amplitude (P<0.001), kep (P=0.03) and AUC (P<0.001) were significantly higher in tumors. tlag did not discriminate carcinomas from glandular tissue. VD was higher in tumors than in the non-affected peripheral prostate (P=0.05). However, none of the dynamic parameters in carcinomas showed a significant correlation with VD or Gleason score. Although pharmacokinetic modeling in DCE MRI showed potential to discriminate prostate cancers from peripheral prostate tissue, descriptive parameters of the early signal enhancement after contrast media injection reached higher sensitivity and specificity.

MR Coil Design for Simultaneous Tip Tracking and Curvature Delineation of a Catheter

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jul, 2004  |  Pubmed ID: 15236390

In active catheter tracking, small RF coils are attached to the catheter for localization. For interactive catheter steering at vessel branchings, it is necessary to visualize not only a single point near the catheter tip but also the entire shape and orientation of the catheter's distal end. Therefore, a 35-mm-long twisted-pair RF coil was added to a 5 French intravascular catheter with a single tip-tracking coil. With the use of small nonmagnetic electronic components at the catheter tip, and a special switching circuitry outside the catheter, the coil assembly could be operated in two different modes. During MRI, the tip-tracking coil was detuned so that the MR signal was received by the visualization coil only. During tracking, detuning was switched off and the MR signal was predominantly received by the more sensitive tracking coil. The catheter was used in combination with a MR pulse sequence with automatic slice positioning so that the current imaging slice was always placed at the position of the catheter tip. Phantom and animal experiments showed that the catheter tip is better visualized with the combined approach than with a tracking coil alone.

Experimental Study of the Rat for the Assessment of Barium Coating on the Gastric Mucosa: Efficacy of Ranitidine and Acetylcysteine Administration

Radiation Medicine. May-Jun, 2004  |  Pubmed ID: 15287533

In order to improve the preparation method for barium examination of the stomach by ranitidine and acetylcysteine use, the effect on the rat gastric mucosa caused by the administration of ranitidine and acetylcysteine was studied.

[The Nobel Prize in "Physiology or Medicine" 2003 for the Discoveries Concerning Magnetic Resonance Imaging]

Zeitschrift Für Medizinische Physik. 2004  |  Pubmed ID: 15323285

Semiquantitative Fast Flow Velocity Measurements Using Catheter Coils with a Limited Sensitivity Profile

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Sep, 2004  |  Pubmed ID: 15334577

Flow measurements can be used to quantify blood flow during MR-guided intravascular interventional procedures. In this study, a fast flow measurement technique is proposed that quantifies flow velocities in the vicinity of a small RF coil attached to an intravascular catheter. Since the small RF coil receives signal from only a limited volume around the catheter, a spatially nonselective signal reception is employed. To enhance signal from flowing blood, and suppress unwanted signal contributions from static material, a slice-selective RF excitation is used. At a velocity sensitivity of 150 cm/s, a temporal resolution of 2 x TR = 10.2 ms can be achieved. The flow measurement is combined with an automatic slice positioning to facilitate measurements during interventional procedures. The influence of the catheter position in the blood vessel on the velocity measurement was analyzed in simulations. For blood vessels with laminar flow, the simulation showed a systematic deviation between catheter measurement and true flow between -15% and 80%. In four animal experiments, the catheter velocity measurement was compared with results from a conventional ECG-triggered 2D phase-contrast (PC) technique. The shapes of the velocity time curves in the abdominal aorta were nearly identical to the conventional measurements. A relative scaling factor of 0.69-1.19 was found between the catheter velocity measurement and the reference measurement, which could be partly explained by the simulation results.

Volumetric Computed Tomography (VCT): a New Technology for Noninvasive, High-resolution Monitoring of Tumor Angiogenesis

Nature Medicine. Oct, 2004  |  Pubmed ID: 15361864

Volumetric computed tomography (VCT) is a technology in which area detectors are used for imaging large volumes of a subject with isotropic imaging resolution. We are experimenting with a prototype VCT scanner that uses flat-panel X-ray detectors and is designed for high-resolution three-dimensional (3D) imaging. Using this technique, we have demonstrated microangiography of xeno-transplanted skin squamous cell carcinomas in nude mice. VCT shows the vessel architecture of tumors and animals with greater detail and plasticity than has previously been achieved, and is superior to contrast-enhanced magnetic resonance (MR) angiography. VCT and MR images correlate well for larger tumor vessels, which are tracked from their origin on 3D reconstructions of VCT images. When compared with histology, small tumor vessels with a diameter as small as 50 microm were clearly visualized. Furthermore, imaging small vessel networks inside the tumor tissue improved discrimination of vital and necrotic regions. Thus, VCT substantially improves imaging of vascularization in tumors and offers a promising tool for preclinical studies of tumor angiogenesis and antiangiogenic therapies.

Improved Correlation of Histological Data with DCE MRI Parameter Maps by 3D Reconstruction, Reslicing and Parameterization of the Histological Images

European Radiology. Jun, 2005  |  Pubmed ID: 15747142

Due to poor correlation of slice thickness and orientation, verification of radiological methods with histology is difficult. Thus, a procedure for three-dimensional reconstruction, reslicing and parameterization of histological data was developed, enabling a proper correlation with radiological data. Two different subcutaneous tumors were examined by MR microangiography and DCE-MRI, the latter being post-processed using a pharmacokinetic two-compartment model. Subsequently, tumors were serially sectioned and vessels stained with immunofluorescence markers. A ray-tracing algorithm performed three-dimensional visualization of the histological data, allowing virtually reslicing to thicker sections analogous to MRI slice geometry. Thick slices were processed as parameter maps color coding the marker density in the depth of the slice. Histological 3D reconstructions displayed the diffuse angioarchitecture of malignant tumors. Resliced histological images enabled specification of high enhancing areas seen on MR microangiography as large single vessels or vessel assemblies. In orthogonally reconstructed histological slices, single vessels were delineated. ROI analysis showed significant correlation between histological parameter maps of vessel density and MR parameter maps (r=0.83, P=0.05). The 3D approach to histology improves correlation of histological and radiological data due to proper matching of slice geometry. This method can be used with any histological stain, thus enabling a multivariable correlation of non-invasive data and histology.

[Measurements of Respiratory Motion Using Fast Magnetic Resonance Imaging and Inductively-coupled Marker Coils]

Zeitschrift Für Medizinische Physik. 2005  |  Pubmed ID: 15830783

The respiratory motion of the thoracic wall provides indirect information about the breathing displacement of the inner organs. To analyze the correlation between thoracic wall and lung motion for applications in radiation therapy, the breathing displacement of the lung is visualized with a fast gradient echo pulse sequence (trueFISP) at a rate of 2-3 images/sec. For quantification of the motion, a small inductively-coupled marker coil is attached to the chest wall and detected with a fast projection technique. Since the marker coil generates a flip angle amplification (factor 15) in its interior, very small nominal flip angles of 2 degrees can be used during the projection measurements which do not affect the image quality of the trueFISP images. Volunteer studies with the marker coil showed a good agreement with simultaneously acquired breathing belt data and position information extracted from the MR images. Whereas the breathing belt provided reliable data only within a certain dynamic range, the marker coil could detect also extreme breathing excursions with a precision better than 2 millimeters.

Influence of Different Breathing Maneuvers on Internal and External Organ Motion: Use of Fiducial Markers in Dynamic MRI

International Journal of Radiation Oncology, Biology, Physics. May, 2005  |  Pubmed ID: 15850927

To investigate, with dynamic magnetic resonance imaging (dMRI) and a fiducial marker, the influence of different breathing maneuvers on internal organ and external chest wall motion.

Physical and Biological Characterization of Superparamagnetic Iron Oxide- and Ultrasmall Superparamagnetic Iron Oxide-labeled Cells: a Comparison

Investigative Radiology. Aug, 2005  |  Pubmed ID: 16024988

Superparamagnetic iron-oxide particles are used frequently for cellular magnetic resonance imaging and in vivo cell tracking. The purpose of this study was to compare the labeling characteristics and efficiency as well as toxicity of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) for 3 cell lines.

Quantification of Aortic Elasticity: Development and Experimental Validation of a Method Using Computed Tomography

European Radiology. Dec, 2005  |  Pubmed ID: 16044295

Aortic distensibility depending on aortic cross-sectional area changes is an important parameter for the grading of vascular diseases. This study measured aortic area changes by multidetector computed tomography. An image reconstruction algorithm was developed to assess aorta diameter and area as a function of the cardiac cycle with sufficient time resolution along the entire length of the aorta by four-detector row computed tomography. The algorithm was tested on porcine aortic specimens and compared with an optical reference method. The error of the relative vessel area change comparing the two methods was found to be about 3%. Initial tests on patient datasets indicate that clinical application is feasible. The proposed method has the advantage that it can easily be integrated into a modified routine CT angiography study and allows the measurement of aortic cross-sectional area changes.

[Status and Perspectives of Non Invasive Cell Tracking]

Zeitschrift Für Medizinische Physik. 2005  |  Pubmed ID: 16171038

The interaction of different cells is an important regulator in the development of many diseases, including cancer. Some cells are recruited directly from the local tissue environment, others reach the pathological focus via the circulation. Using non-invasive cell tracking methods, the distribution and migration of labeled cells can be studied in experimental animal models, and the role of these cells on the pathogenesis of disease can thus be elucidated. Scintigraphy and SPECT, and especially MRI and optical imaging, are frequently used for this purpose. Studies are mostly performed with macrophages and granulocytes (inflammatory cells), which accumulate in nephritis, encephalitis, and tumors. At present, the understanding of progenitor cell migration and differentiation is gaining increasing interest in neurological disorders (for example Parkinson's disease) and in cardiac diseases (for example myocardial infarction). Non-invasive cell tracking is already established in basic research; in the future, a clinical application of cell tracking is foreseeable in the framework of cell therapy.

[Principles of Optical and Fluorescence Mediated Tomography in Turbid Media]

Zeitschrift Für Medizinische Physik. 2005  |  Pubmed ID: 16171039

Three-dimensional, tomographic imaging of biological tissues by means of visible light is becoming increasingly important. Current progress in the mathematical-physical modelling of photon propagation in scattering media allows spatially-resolved reconstructions of optical parameters with common computing hardware. Especially in the field of molecular imaging, optical tomography promises a transfer of knowledge from successful in vitro assays (as evaluated by fluorescence microscopy) to in vivo imaging of living animals. In the latter case, spatial resolution is not as critical as the ability to quantify the concentration of fluorescence-labelled probes, a task not solvable by the use of common planar imaging techniques. In this article, the theoretical foundations of optical tomography are introduced along with some examples of applications.

Potential Applications of Flat-panel Volumetric CT in Morphologic and Functional Small Animal Imaging

Neoplasia (New York, N.Y.). Aug, 2005  |  Pubmed ID: 16207475

Noninvasive radiologic imaging has recently gained considerable interest in basic and preclinical research for monitoring disease progression and therapeutic efficacy. In this report, we introduce flat-panel volumetric computed tomography (fpVCT) as a powerful new tool for noninvasive imaging of different organ systems in preclinical research. The three-dimensional visualization that is achieved by isotropic high-resolution datasets is illustrated for the skeleton, chest, abdominal organs, and brain of mice. The high image quality of chest scans enables the visualization of small lung nodules in an orthotopic lung cancer model and the reliable imaging of therapy side effects such as lung fibrosis. Using contrast-enhanced scans, fpVCT displayed the vascular trees of the brain, liver, and kidney down to the subsegmental level. Functional application of fpVCT in dynamic contrast-enhanced scans of the rat brain delivered physiologically reliable data of perfusion and tissue blood volume. Beyond scanning of small animal models as demonstrated here, fpVCT provides the ability to image animals up to the size of primates.

Optical Molecular Imaging of Lymph Nodes Using a Targeted Vascular Contrast Agent

Journal of Biomedical Optics. Jul-Aug, 2005  |  Pubmed ID: 16178629

We develop a highly specific antibody-dye conjugate for optical imaging of peripheral lymph nodes. The contrast agent consists of the monoclonal antibody recognizing endothelial ligands for the lymphocyte homing receptor L-selectin, MECA-79, and a near-infrared (near-IR) fluorescent indotricarbocyanine dye. The targeting and biodistribution behavior of MECA-79 is studied after radio-iodination and intravenous injection into mice demonstrating specific uptake in lymph nodes and accumulation in high endothelial venules (HEV). After conjugation of MECA-79 with indotricarbocyanine dye, the fluorescence imaging properties of the MECA-79 dye conjugate are examined by intravenous injection in nude mice and laser-induced fluorescence whole-body imaging in vivo. The MECA-79 antibody-dye conjugate accumulates in peripheral lymph nodes, whereas an isotype antibody-dye conjugate does not. Specific lymph node near-IR fluorescent signals become detectable within minutes after injection, and stable imaging persists for more than 24 h. The results demonstrate that vascular targeting of endothelial expression of glyocproteins is feasible to visualize the accumulation of near-IR fluorescent MECA-79 in lymph nodes, making this technology potentially useful to characterize processes of inflammation.

Synthesis and Characterization of HE-24.8: a Polymeric Contrast Agent for Magnetic Resonance Angiography

Bioconjugate Chemistry. Jan-Feb, 2006  |  Pubmed ID: 16417250

The physical and biological properties of a water-soluble polymeric contrast agent based on a complex of N-(2-hydroxypropyl)methacrylamide copolymer with gadolinium (HE-24.8) were investigated, and its potential for experimental magnetic resonance (MR) angiography was assessed. Relaxivities of Gd-DTPA-BMA, Gd-DTPA-HSA (human serum albumin), and HE-24.8 were determined at 1.5 T. Thermic stability and biocompatibility of HE-24.8 were assessed in vitro and by analyzing kinetics and organ distribution in rats for up to 2 weeks. For comparison, HE-24.8- and Gd-DTPA-HSA-enhanced micro-MR angiographies of brain, chest, and subcutaneous tumors in rats were performed. T1 relaxivity of HE-24.8 (21.3 +/- 1.1 mM(-1) s(-1)) was 5-fold higher than that of Gd-DTPA-BMA (4.1 +/- 0.1 mM(-1) s(-1)) and twice as high as that of Gd-DTPA-HSA (12.4 +/- 0.2 mM(-1) s(-1)). Varying the molecular weight of the polymer (15-46 kDa) did not significantly change the T1 relaxivity. In rats, 20 and 10% of the injected dose of HE-24.8 was detected at 24 and 168 h postinjection, respectively. Upon a relatively rapid initial renal clearance, no specific retention in any organ was noted, with some exception for the reticulo-endothelial system. No measurable release of gadolinium from the polymer-Gd complex or cell toxicity was observed during its incubation in aqueous environment. Excellent display of rat and tumor vascularization was achieved with Gd-DTPA-HSA and HE-24.8; however, contrast of vessels was higher in HE-24.8-enhanced scans. HE-24.8 is considered a macromolecular contrast agent highly suited for experimental MR studies.

Comparison of Noncontact and Fiber-based Fluorescence-mediated Tomography

Optics Letters. Mar, 2006  |  Pubmed ID: 16544618

We present a comparative experimental phantom study of fiber-based and noncontact fluorescence tomography with respect to quantitation and localization of reconstructed fluorescent inclusions in turbid media such as tissue. Noncontact acquisition is usually considered potentially superior to fiber-based techniques because of the availability of a large number of detector readouts through a CCD. Our results indicate, however, that noncontact acquisition itself might improve the quality of reconstructions significantly, even without increasing the number of detectors and thus keeping the inverse problem moderately complex.

Active Catheter Tracking Using Parallel MRI and Real-time Image Reconstruction

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jun, 2006  |  Pubmed ID: 16683261

In this work active MR catheter tracking with automatic slice alignment was combined with an autocalibrated parallel imaging technique. Using an optimized generalized autocalibrating partially parallel acquisitions (GRAPPA) algorithm with an acceleration factor of 2, we were able to reduce the acquisition time per image by 34%. To accelerate real-time GRAPPA image reconstruction, the coil sensitivities were updated only after slice reorientation. For a 2D trueFISP acquisition (160 x 256 matrix, 80% phase matrix, half Fourier acquisition, TR = 3.7 ms, GRAPPA factor = 2) real-time image reconstruction was achieved with up to six imaging coils. In a single animal experiment the method was used to steer a catheter from the vena cava through the beating heart into the pulmonary vasculature at an image update rate of about five images per second. Under all slice orientations, parallel image reconstruction was accomplished with only minor image artifacts, and the increased temporal resolution provided a sharp delineation of intracardial structures, such as the papillary muscle.

From 2D PET to 3D PET: Issues of Data Representation and Image Reconstruction

Zeitschrift Für Medizinische Physik. 2006  |  Pubmed ID: 16696369

Positron emission tomography (PET), intrinsically a 3D imaging technique, was for a long time exclusively operated in 2D mode, using septa to shield the detectors from photons emitted obliquely to the detector planes. However, the use of septa results in a considerable loss of sensitivity. From the late 1980s, significant efforts have been made to develop a methodology for the acquisition and reconstruction of 3D PET data. This paper focuses on the differences between data acquisition in 2D and 3D mode, especially in terms of data set sizes and representation. Although the real time data acquisition aspect in 3D has been mostly solved in modern PET scanner systems, there still remain questions on how to represent and how to make best use of the information contained in the acquired data sets. Data representation methods, such as list-mode and matrix-based methods, possibly with additional compression, will be discussed. Moving from 2D to 3D PET has major implications on the way these data are reconstructed to images. Two fundamentally different approaches exist, the analytical one and the iterative one. Both, at different expenses, can be extended to directly handle 3D data sets. Either way the computational burden increases heavily compared to 2D reconstruction. One possibility to benefit from the increased sensitivity in 3D PET while sticking to high-performance 2D reconstruction algorithms is to rebin 3D into 2D data sets. The value of data rebinning will be explored. An ever increasing computing power and the concept of distributed or parallel computing have made direct 3D reconstruction feasible. Following a short review of reconstruction methods and their extensions to 3D, we focus on numerical aspects that improve reconstruction performance, which is especially important in solving large equation systems in 3D iterative reconstruction. Finally exemplary results are shown to review the properties of the discussed algorithms. This paper concludes with an overview on future trends in data representation and reconstruction.

Dynamic Coil Selection for Real-time Imaging in Interventional MRI

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Nov, 2006  |  Pubmed ID: 17029224

MR-guided intravascular interventions require image update rates of up to 10 images per second, which can be achieved using parallel imaging. However, parallel imaging requires many coil elements, which increases reconstruction times and thus compromises real-time image reconstruction. In this study a dynamic coil selection (DCS) algorithm is presented that selects a subset of receive coils to reduce image reconstruction times. The center-of-sensitivity coordinates and the relative signal intensities are determined for each coil in a prescan. During the intervention m coils are selected for reconstruction using a coil ranking based on the distance to the current slice or catheter position. In a phantom experiment for m = 6, an optimal signal-to-background ratio (SBR) was achieved and foldover artifacts were avoided. In three animal experiments involving catheter manipulation in the aorta and the right heart chamber, the anatomy was successfully visualized at frame rates of about 5 Hz using active catheter tracking.

Dual-bolus Approach to Quantitative Measurement of Pulmonary Perfusion by Contrast-enhanced MRI

Journal of Magnetic Resonance Imaging : JMRI. Dec, 2006  |  Pubmed ID: 17051533

To evaluate a dual-bolus approach to pulmonary perfusion MRI.

B1 Field-insensitive Transformers for RF-safe Transmission Lines

Magma (New York, N.Y.). Nov, 2006  |  Pubmed ID: 17115123

Integration of transformers into transmission lines suppresses radiofrequency (RF)-induced heating. New figure-of-eight-shaped transformer coils are compared to conventional loop transformer coils to assess their signal transmission properties and safety profile.

Silica- and Alkoxysilane-coated Ultrasmall Superparamagnetic Iron Oxide Particles: a Promising Tool to Label Cells for Magnetic Resonance Imaging

Langmuir : the ACS Journal of Surfaces and Colloids. Jan, 2007  |  Pubmed ID: 17241069

In this study silica- and alkoxysilane-coated ultrasmall superparamagnetic iron oxide (USPIO) particles were synthesized, and their ability to label immortalized progenitor cells for magnetic resonance imaging (MRI) was compared. USPIO particles were synthesized by coprecipitation of ferric and ferrous salts. Subsequently, the particles were coated with silica, (3-aminopropyl)trimethoxysilane (APTMS), and [N-(2-aminoethyl)-3-aminopropyl]trimethoxysilane (AEAPTMS). The size of the USPIO particles was about 10 nm without a significant increase in diameter after coating. The highest T2 relaxivity was achieved for silica-coated USPIO particles, 339.80 +/- 0.22 s-1 mM-1, as compared with APTMS- and AEAPTMS-coated ones, reaching 134.40 +/- 0.01 and 84.79 +/- 0.02 s-1 mM-1, respectively. No toxic effects on the cells could be detected by trypan blue, TUNEL, and MTS assays. Uptake of USPIO particles was evaluated by Prussian blue staining, transmission electron microscopy, T2-MR relaxometry, and mass spectrometry. It was found that cell uptake of the different USPIO particles increased for longer incubation times and higher doses. Maximum cellular iron concentrations of 42.1 +/- 4.0 pg/cell (silica-coated USPIO particles), 37.1 +/- 3.5 pg/cell (APTMS-coated USPIO particles), and 32.7 +/- 4.0 pg/cell (AEAPTMS-coated USPIO particles) were achieved after incubation of the cells with USPIO particles at a dose of 3 micromol/mL for 6 h. The decrease of the T2 relaxation time of the cell pellets was most pronounced for cells incubated with silica-coated USPIO particles followed by APTMS- and AEAPTMS-coated particles, respectively. In gelatin gels even small clusters of labeled cells were detected by 1.5 T MRI, and significant changes in the T2 relaxation times of the gels were determined for 10000 labeled cells/mL for all particles. In summary, as compared with APTMS- and AEAPTMS-coated particles, silica-coated USPIO particles provide the highest T2 relaxivity and most effectively reduce the T2 relaxation time of immortalized progenitor cells after internalization. This suggests silica-coated USPIO particles are most suited for cell labeling approaches in MRI.

Specific Targeting of Tumor Angiogenesis by RGD-conjugated Ultrasmall Superparamagnetic Iron Oxide Particles Using a Clinical 1.5-T Magnetic Resonance Scanner

Cancer Research. Feb, 2007  |  Pubmed ID: 17308094

Angiogenesis is essential for the development of malignant tumors and provides important targets for tumor diagnosis and therapy. To noninvasively assess the angiogenic profile of tumors, novel alpha(v)beta(3) integrin-targeted ultrasmall superparamagnetic iron oxide particles (USPIOs) were designed and their specific uptake by endothelial cells was evaluated in vitro and in vivo. USPIOs were coated with 3-aminopropyltrimethoxysilane (APTMS) and conjugated with Arg-Gly-Asp (RGD) peptides. Accumulation in human umbilical vein endothelial cells (HUVECs) was evaluated using Prussian blue staining, transmission electron microscopy, magnetic resonance (MR) imaging, and inductively coupled plasma mass spectrometry. Uptake of RGD-USPIO by HUVECs was significantly increased when compared with unlabeled USPIO and could be competitively inhibited by addition of unbound RGD. The ability of the RGD-USPIO to noninvasively distinguish tumors with high (HaCaT-ras-A-5RT3) and lower (A431) area fractions of alpha(v)beta(3) integrin-positive vessels was evaluated using a 1.5-T MR scanner. Indeed, after RGD-USPIO injection, there was a more pronounced decrease in T(2) relaxation times in HaCaT-ras-A-5RT3 tumors than in A431 tumors. Furthermore, T(2)*-weighted images clearly identified the heterogeneous arrangement of vessels with alpha(v)beta(3) integrins in HaCaT-ras-A-5RT3 tumors by an irregular signal intensity decrease. In contrast, in A431 tumors with predominantly small and uniformly distributed vessels, the signal intensity decreased more homogeneously. In summary, RGD-coupled, APTMS-coated USPIOs efficiently label alpha(v)beta(3) integrins expressed on endothelial cells. Furthermore, these molecular MR imaging probes are capable of distinguishing tumors differing in the degree of alpha(v)beta(3) integrin expression and in their angiogenesis profile even when using a clinical 1.5-T MR scanner.

Impact of Stroma on the Growth, Microcirculation, and Metabolism of Experimental Prostate Tumors

Neoplasia (New York, N.Y.). Jan, 2007  |  Pubmed ID: 17325744

In prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations of hormone-sensitive (H), hormone-insensitive (HI), and anaplastic (AT1) Dunning PCa in rats on growth, microcirculation, and metabolism was investigated. For this purpose, dynamic contrast-enhanced magnetic resonance imaging and (1)H magnetic resonance spectroscopy ([(1)H]MRS) were applied in combination with histology. Consistent observations revealed that orthotopic H tumors grew significantly slower compared to subcutaneous ones, whereas the growth of HI and AT1 tumors was comparable at both locations. Histologic analysis indicated that glandular differentiation and a close interaction of tumor cells and smooth muscle cells (SMC) were associated with slow tumor growth. Furthermore, there was a significantly lower SMC density in subcutaneous H tumors than in orthotopic H tumors. Perfusion was observed to be significantly lower in orthotopic H tumors than in subcutaneous H tumors. Regional blood volume and permeability-surface area product showed no significant differences between tumor models and their implantation sites. Differences in growth between subcutaneous and orthotopic H tumors can be attributed to tumor-stroma interaction and perfusion. Here, SMC, may stabilize glandular structures and contribute to the maintenance of differentiated phenotype.

[An Algorithm for Passive Marker Localization in Interventional MRI]

Zeitschrift Für Medizinische Physik. 2007  |  Pubmed ID: 17879815

The localization of passive marker systems in interventional MRI is necessary to monitor the position and orientation of medical instruments that do not emit an MR signal. In this work an algorithm is presented that automatically detects a given marker system in an MR image with a precision better than one pixel. Therefore, a combination of a phase-only cross correlation algorithm with a subsequent center-of-mass analysis is utilized. The algorithm was evaluated in simulations and phantom experiments with respect to precision, noise sensitivity as well as the influence of unwanted signal amplitudes. Above a signal-to-noise ratio (SNR) of 4.5 a localization precision significantly better than the pixel dimension could be achieved. For SNR values of 6 and more the influence of unwanted signals on the localization could not be detected in the simulations. In phantom experiments the predicted precision of the marker localization could be realized which results for typical measurement parameters in a maximal deviation of the needle tip in an MR-guided needle injection of 0.6 mm.

Retrospective Motion Gating in Small Animal CT of Mice and Rats

Investigative Radiology. Oct, 2007  |  Pubmed ID: 17984768

Implementation and evaluation of retrospective respiratory and cardiac gating of mice and rats using a flat-panel volume-CT prototype (fpVCT).

Volumetric High-frequency Doppler Ultrasound Enables the Assessment of Early Antiangiogenic Therapy Effects on Tumor Xenografts in Nude Mice

European Radiology. Apr, 2008  |  Pubmed ID: 18084768

The sensitivity of Doppler ultrasound below 10 MHz to assess antiangiogenic therapy effects in tumor xenografts has been shown to be limited. Thus, our aim was to evaluate high-frequency volumetric power-Doppler ultrasound (HF-VPDU) for monitoring antiangiogenic treatments. Squamous cell carcinoma xenografts grown in nude mice were scanned with HF-VPDU at a center frequency of 30 MHz. Images with 200-microm slice thicknesses were recorded and merged into a three-dimensional dataset, of which the relative color pixel density was determined. Animals received either VEGFR2 antibodies or 0.9% NaCl and were examined at days 0, 3 and 6 of treatment. After the last examination, tumors were resected and their vascularization characterized by immunohistology. At day 6, the volumes of treated and untreated tumors were not significantly different yet. In contrast, mean tumor vascularization in treated animals had decreased to 44%, while in the control group it had increased to 152% (P < 0.01). In correspondence, vessel density, as determined by CD31 staining, was 0.19 +/- 0.10% in treated and 0.92 +/- 0.41% in untreated tumors (P < 0.01). Additionally, the fraction of mature (SMA-positive) vessels increased under therapy. Thus, HF-VPDU can be considered as an easily applicable and fast method to screen high animal numbers for antiangiogenic therapy effects.

Molecular Profiling of Angiogenesis with Targeted Ultrasound Imaging: Early Assessment of Antiangiogenic Therapy Effects

Molecular Cancer Therapeutics. Jan, 2008  |  Pubmed ID: 18202013

Molecular ultrasound is capable of elucidating the expression of angiogenic markers in vivo. However, the capability of the method for volumetric "multitarget quantification" and for the assessment of antiangiogenic therapy response has rather been investigated. Therefore, we generated cyanoacrylate microbubbles linked to vascular endothelial growth factor receptor 2 (VEGFR2) and alphavbeta3 integrin binding ligands and quantified their accumulation in squamous cell carcinoma xenografts (HaCaT-ras-A-5RT3) in mice with the quantitative volumetric ultrasound scanning technique, sensitive particle acoustic quantification. Specificity of VEGFR2 and alphavbeta3 integrin binding microbubbles was shown, and changes in marker expression during matrix metalloproteinase inhibitor treatment were investigated. In tumors, accumulation of targeted microbubbles was significantly higher compared with nonspecific ones and could be inhibited competitively by addition of the free ligand in excess. Also, multimarker imaging could successfully be done during the same imaging session. Molecular ultrasound further indicated a significant increase of VEGFR2 and alphavbeta3 integrin expression during tumor growth and a considerable decrease in both marker densities after matrix metalloproteinase inhibitor treatment. Histologic data suggested that the increasing VEGFR2 and alphavbeta3 integrin concentrations in tumors during growth are related to an up-regulation of its expression by the endothelial cells, whereas its decrease under therapy is more related to the decreasing relative vessel density. In conclusion, targeted ultrasound appears feasible for the longitudinal molecular profiling of tumor angiogenesis and for the sensitive assessment of therapy effects in vivo.

Pharmacodynamics of Streptavidin-coated Cyanoacrylate Microbubbles Designed for Molecular Ultrasound Imaging

Investigative Radiology. Mar, 2008  |  Pubmed ID: 18301312

To assess the pharmacodynamic behavior of cyanoacrylate, streptavidin-coated microbubbles (MBs) and to investigate their suitability for molecular ultrasound imaging.

Automatic Passive Tracking of an Endorectal Prostate Biopsy Device Using Phase-only Cross-correlation

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. May, 2008  |  Pubmed ID: 18429016

MR-guided transrectal prostate biopsy is currently a time-consuming procedure because the imaging slice is often manually realigned with the biopsy needle during lesion targeting. In this work a pulse sequence is presented that automatically follows a passive marker attached to a dedicated MR biopsy device holder, thus providing an alternative to existing active tracking methods. In two orthogonal tracking FLASH images of the marker the position of the needle axis is automatically identified using a phase-only cross-correlation (POCC) algorithm. The position information is then used to realign a trueFISP imaging slice in real time. In phantom experiments the sensitivity of this technique to initial misalignments of the marker and to the signal-to-noise ratio was evaluated. In several puncture experiments the precision of the needle placement was analyzed. The POCC algorithm allowed for a precise identification of the marker in the images even under severe initial misalignments of up to 45 degrees. At a frame rate 1 image/s a precision of the needle placement of 1.5 +/- 1.1 mm could be achieved.

Intrinsic Respiratory Gating in Small-animal CT

European Radiology. Jul, 2008  |  Pubmed ID: 18431578

Gating in small-animal CT imaging can compensate artefacts caused by physiological motion during scanning. However, all published gating approaches for small animals rely on additional hardware to derive the gating signals. In contrast, in this study a novel method of intrinsic respiratory gating of rodents was developed and tested for mice (n=5), rats (n=5) and rabbits (n=2) in a flat-panel cone-beam CT system. In a consensus read image quality was compared with that of non-gated and retrospective extrinsically gated scans performed using a pneumatic cushion. In comparison to non-gated images, image quality improved significantly using intrinsic and extrinsic gating. Delineation of diaphragm and lung structure improved in all animals. Image quality of intrinsically gated CT was judged to be equivalent to extrinsically gated ones. Additionally 4D datasets were calculated using both gating methods. Values for expiratory, inspiratory and tidal lung volumes determined with the two gating methods were comparable and correlated well with values known from the literature. We could show that intrinsic respiratory gating in rodents makes additional gating hardware and preparatory efforts superfluous. This method improves image quality and allows derivation of functional data. Therefore it bears the potential to find wide applications in small-animal CT imaging.

In Vivo Gd-DTPA Concentration for MR Lung Perfusion Measurements: Assessment with Computed Tomography in a Porcine Model

European Radiology. Oct, 2008  |  Pubmed ID: 18446343

A linear relationship between MR signal and contrast-agent concentration (CAC) of the arterial-input function (AIF) is crucial for MR lung-perfusion quantification. The aim was to determine the in-vivo real maximum CAC of the AIF, using cine CT measurements in a porcine model. A dilution series (Gd-DTPA, 0-20 mM) was examined by clinical time-resolved 3D-GRE MRI and by MDCT in cine CT mode. Using the CT setup, data were acquired in five pigs immediately after the injection of 0.05 mmol and 0.07 mmol/kg BW Gd-DTPA. For phantom measurements, mean signal values were determined using a region-of-interest (ROI) analysis and for animal measurements, a ROI was placed in the pulmonary trunk of the cine CT perfusion data sets. The CT phantom measurements were used to calculate the in-vivo maximum CAC corresponding to the HU values obtained in the pulmonary trunk by the cine CT study. Linearity of the AIF of the CT perfusion measurements was verified using the MR phantom measurement results. MR phantom measurements demonstrated linearity for concentrations of 0-4 mM. CT phantom measurements showed linear relation for the entire CAC range. Comparing in-vivo and in-vitro measurements, three of five CA injections at 0.05 mmol/kg and all 0.07 mmol/kg injections exceeded the range of linearity in MRI. The CA dose for quantification of lung perfusion with time-resolved MR studies must be chosen carefully since even with low doses (0.05 mmol/kg) the CAC may exceed the range of linearity in the AIF.

Fundamentals of Optical Imaging

Handbook of Experimental Pharmacology. 2008  |  Pubmed ID: 18626796

Optical imaging techniques offer simplistic while highly sensitive modalities for molecular imaging research. In this chapter, the major instrumental necessities for microscopic and whole-animal imaging techniques are introduced. Subsequently, the resulting imaging modalities using visible or near-infrared light are presented and discussed. The aim is to show the current capabilities and application fields of optics.

Flow-compensated Self-gating

Magma (New York, N.Y.). Sep, 2008  |  Pubmed ID: 18668271

Self-gating (SG) is a method to record cardiac movement during MR imaging. It uses information from an additional short, non-spatially encoded data acquisition. This usually lengthens TE and increases the sensitivity to flow artifacts. A new flow compensation scheme optimized for self-gating sequences is introduced that has very little or no time penalty over self-gating sequences without flow compensation.

Vessel Fractions in Tumor Xenografts Depicted by Flow- or Contrast-sensitive Three-dimensional High-frequency Doppler Ultrasound Respond Differently to Antiangiogenic Treatment

Cancer Research. Sep, 2008  |  Pubmed ID: 18757418

High-frequency volumetric Power Doppler ultrasound (HF-VPDU) captures flow-dependent signals in blood vessels and can be used to assess antiangiogenic therapy effects in rodent tumors. However, the sensitivity is limited to vessels larger than capillaries. Contrast-enhanced HF-VPDU reveals all perfused vessels by assessing stimulated acoustic emissions from disintegrating microbubbles. Thus, we investigated whether flow-sensitive and contrast-enhanced HF-VPDU can depict different vessel fractions and assess their early response to antiangiogenic therapy. Mice with A431 tumors were scanned before and after administration of polybutylcyanoacrylate microbubbles by HF-VPDU. Animals received either antiangiogenic treatment (SU11248) or a control substance and were imaged repeatedly over 9 days. At each time point, tumors were removed for immunohistochemical analysis. During growth of untreated tumors, vascularization decreased correspondingly on flow-sensitive and contrast-enhanced scans. Treated tumors showed a significantly (P < 0.05) stronger decline in vascularization than controls, which was more pronounced in contrast-enhanced scans. Surprisingly, whereas vascularization remained low in contrast-enhanced scans, flow-sensitive ultrasound indicated a reincrease after day 6 with a higher vascularization than the controls at day 9. Histologic evaluation indicated that immature vessels degraded markedly on therapy, whereas large mature vessels on the tumor periphery were more therapy resistant and drew closer due to tumor shrinkage. In conclusion, contrast-enhanced HF-VPDU and flow-sensitive HF-VPDU are both capable of assessing the effects of antiangiogenic therapy. Because contrast-sensitive ultrasound is more sensitive for small immature vessels and flow-sensitive ultrasound mostly captures large vessels at the tumor periphery, the combination of both methods can provide evidence of vascular maturity in tumors.

Molecular Imaging I. Preface

Handbook of Experimental Pharmacology. 2008  |  Pubmed ID: 18763375

Molecular Imaging II. Preface

Handbook of Experimental Pharmacology. 2008  |  Pubmed ID: 18788125

Intrinsic Gating for Small-animal Computed Tomography: a Robust ECG-less Paradigm for Deriving Cardiac Phase Information and Functional Imaging

Circulation. Cardiovascular Imaging. Nov, 2008  |  Pubmed ID: 19808548

A projection-based method of intrinsic cardiac gating in small-animal computed tomography imaging is presented.

Measurement of R1 Dynamics Using Sliding Window-DESPOT

Journal of Magnetic Resonance Imaging : JMRI. Nov, 2009  |  Pubmed ID: 19856450

To measure longitudinal relaxation rate (R1) changes during contrast agent studies using a driven equilibrium single pulse observation of T1 (DESPOT) method with a sliding window (sw) acquisition.

Sodium MRI Using a Density-adapted 3D Radial Acquisition Technique

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Dec, 2009  |  Pubmed ID: 19859915

A density-adapted three-dimensional radial projection reconstruction pulse sequence is presented which provides a more efficient k-space sampling than conventional three-dimensional projection reconstruction sequences. The gradients of the density-adapted three-dimensional radial projection reconstruction pulse sequence are designed such that the averaged sampling density in each spherical shell of k-space is constant. Due to hardware restrictions, an inner sphere of k-space is sampled without density adaption. This approach benefits from both the straightforward handling of conventional three-dimensional projection reconstruction sequence trajectories and an enhanced signal-to-noise ratio (SNR) efficiency akin to the commonly used three-dimensional twisted projection imaging trajectories. Benefits for low SNR applications, when compared to conventional three-dimensional projection reconstruction sequences, are demonstrated with the example of sodium imaging. In simulations of the point-spread function, the SNR of small objects is increased by a factor 1.66 for the density-adapted three-dimensional radial projection reconstruction pulse sequence sequence. Using analytical and experimental phantoms, it is shown that the density-adapted three-dimensional radial projection reconstruction pulse sequence allows higher resolutions and is more robust in the presence of field inhomogeneities. High-quality in vivo images of the healthy human leg muscle and the healthy human brain are acquired. For equivalent scan times, the SNR is up to a factor of 1.8 higher and anatomic details are better resolved using density-adapted three-dimensional radial projection reconstruction pulse sequence.

Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

Neoplasia (New York, N.Y.). Sep, 2009  |  Pubmed ID: 19724679

Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1) and of alpha(v)beta(3)-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy) was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of alpha(v)beta(3)-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of alpha(v)beta(3)-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and alpha(v)beta(3)-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

Image Formation with a Microlens-based Optical Detector: a Three-dimensional Mapping Approach

Applied Optics. Apr, 2009  |  Pubmed ID: 19340119

A ray-based approach that models the geometric mapping properties of a flat optical detector based on a microlens array is presented. The investigated optical detector substitutes a single-aperture lens optic for planar and tomographic data acquisition in space-constrained small-animal imaging applications. The formalism implements forward mapping of a three-dimensional object volume onto a two-dimensional sensor surface as well as the backprojection (inverse mapping) of acquired sensor data sets. The object focus distance is the sole free parameter for the inverse mapping. By variation of the object focus distance, arbitrary object surface areas within the computed object images can be focused. The inverse mapping algorithm was applied to an experimentally acquired sensor data set from a three-dimensional phantom. The results are compared with focal point image formation.

Assessment of Vascular Remodeling Under Antiangiogenic Therapy Using DCE-MRI and Vessel Size Imaging

Journal of Magnetic Resonance Imaging : JMRI. May, 2009  |  Pubmed ID: 19388117

To assess vascular remodeling in tumors during two different antiangiogenic therapies with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging and to evaluate the vessel size index (VSI) as a novel biomarker of therapy response.

Imaging Response to Systemic Therapy for Bone Metastases

European Radiology. Oct, 2009  |  Pubmed ID: 19468736

In patients with osteotropic primary tumours such as breast and prostate cancer, imaging treatment response of bone metastases is essential for the clinical management. After treatment of skeletal metastases, morphological changes, in particular of bone structure, occur relatively late and are difficult to quantify using conventional X-rays, CT or MRI. Early treatment response in these lesions can be assessed from functional imaging techniques such as dynamic contrast-enhanced techniques by MRI or CT and by diffusion-weighted MRI, which are quantifiable. Among the techniques within nuclear medicine, PET offers the acquisition of quantifiable parameters for response evaluation. PET, therefore, especially in combination with CT and MRI using hybrid techniques, holds great promise for early and quantifiable assessment of treatment response in bone metastases. This review summarises the classification systems and the use of imaging techniques for evaluation of treatment response and suggests parameters for the early detection and quantification of response to systemic therapy.

Suppression of Pulmonary Vasculature in Lung Perfusion MRI Using Correlation Analysis

European Radiology. Nov, 2009  |  Pubmed ID: 19471936

The purpose of the study was to evaluate the feasibility of suppressing the pulmonary vasculature in lung perfusion MRI using cross-correlation analysis (CCA). Perfusion magnetic resonance imaging (MRI) (3D FLASH, TR/TE/flip angle: 0.8 ms/2.1 ms/40 degrees ) of the lungs was performed in seven healthy volunteers at 1.5 Tesla after injection of Gd-DTPA. CCA was performed pixel-wise in lung segmentations using the signal time-course of the main pulmonary artery and left atrium as references. Pixels with high correlation coefficients were considered as arterial or venous and excluded from further analysis. Quantitative perfusion parameters [pulmonary blood flow (PBF) and volume (PBV)] were calculated for manual lung segmentations separately, with the entire left and right lung with all intrapulmonary vessels (IPV) included, excluded manually or excluded using CCA. The application of CCA allowed reliable suppression of hilar and large IPVs. Using vascular suppression by CCA, perfusion parameters were significantly reduced (p

RGD-labeled USPIO Inhibits Adhesion and Endocytotic Activity of Alpha V Beta3-integrin-expressing Glioma Cells and Only Accumulates in the Vascular Tumor Compartment

Radiology. Nov, 2009  |  Pubmed ID: 19789239

To investigate the biologic effect of arginine-glycine-aspartic acid (RGD)-labeled ultrasmall superparamagnetic iron oxide (USPIO) (referred to as RGD-USPIO) on human umbilical vein endothelial cells (HUVECs), ovarian carcinoma (MLS) cells, and glioblastoma (U87MG) cells and on U87MG xenografts in vivo.

Gating in Small-animal Cardio-thoracic CT

Methods (San Diego, Calif.). Jan, 2010  |  Pubmed ID: 19651213

Gating is necessary in cardio-thoracic small-animal imaging because of the physiological motions that are present during scanning. In small-animal computed tomography (CT), gating is mainly performed on a projection base because full scans take much longer than the motion cycle. This paper presents and discusses various gating concepts of small-animal CT, and provides examples of concrete implementation. Since a wide variety of small-animal CT scanner systems exist, scanner systems are discussed with respect to the most suitable gating methods. Furthermore, an overview is given of cardio-thoracic imaging and gating applications. The necessary contrast media are discussed as well as gating limitations. Gating in small-animal imaging requires the acquisition of a gating signal during scanning. This can be done extrinsically (additional hardware, e.g. electrocardiogram) or intrinsically from the projection data itself. The gating signal is used retrospectively during CT reconstruction, or prospectively to trigger parts of the scan. Gating can be performed with respect to the phase or the amplitude of the gating signal, providing different advantages and challenges. Gating methods should be optimized with respect to the diagnostic question, scanner system, animal model, type of narcosis and actual setup. The software-based intrinsic gating approaches increasingly employed give the researcher independence from difficult and expensive hardware changes.

Simulation-based Comparison of Two Approaches Frequently Used for Dynamic Contrast-enhanced MRI

European Radiology. Feb, 2010  |  Pubmed ID: 19727758

PURPOSE: The purpose was to compare two approaches for the acquisition and analysis of dynamic-contrast-enhanced MRI data with respect to differences in the modelling of the arterial input-function (AIF), the dependency of the model parameters on physiological parameters and their numerical stability. Eight hundred tissue concentration curves were simulated for different combinations of perfusion, permeability, interstitial volume and plasma volume based on two measured AIFs and analysed according to the two commonly used approaches. The transfer constants (Approach 1) K (trans) and (Approach 2) k (ep) were correlated with all tissue parameters. K (trans) showed a stronger dependency on perfusion, and k (ep) on permeability. The volume parameters (Approach 1) v (e) and (Approach 2) A were mainly influenced by the interstitial and plasma volume. Both approaches allow only rough characterisation of tissue microcirculation and microvasculature. Approach 2 seems to be somewhat more robust than 1, mainly due to the different methods of CA administration.

An Expandable Catheter Loop Coil for Intravascular MRI in Larger Blood Vessels

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Feb, 2010  |  Pubmed ID: 19918897

The present study proposes a catheter system with an expandable coil etched on a polyimide foil. The catheter system combines the advantages of a small insertion diameter when the coil is rolled up in a protective carrier sheath with an increased signal-to-noise ratio (SNR) and penetration depth when the coil is pushed out. After imaging, the coil can be retracted into the sheath and folded back into the initial rolled-up configuration due to the tapered geometry of the carrier foil. The catheter system was tested on two healthy anesthetized pigs, including tracking and high-resolution intravascular imaging. To reduce artifacts in high-resolution images induced by catheter motion in the pulsatile blood flow, a motion-gating method was implemented that combines a flow-compensated two-dimensional fast low angle shot (FLASH) imaging sequence with the acquisition of projection data for retrospective gating. Using the projection data for motion detection, image SNR was increased by up to 500% over uncorrected images, and anatomic structures of 150 microm size could be differentiated in the aorta.

Comparison of Conventional Time-intensity Curves Vs. Maximum Intensity over Time for Post-processing of Dynamic Contrast-enhanced Ultrasound

European Journal of Radiology. Jul, 2010  |  Pubmed ID: 19945241

Our aim was to prospectively compare two post-processing techniques for dynamic contrast-enhanced ultrasound and to evaluate their impact for monitoring antiangiogenic therapy. Thus, mice with epidermoid carcinoma xenografts were examined during administration of polybutylcyanoacrylate-microbubbles using a small animal ultrasound system (40 MHz). Cine loops were acquired and analyzed using time-intensity (TI) and maximum intensity over time (MIOT) curves. Influences of fast (50 microl/2s) vs. slow (50 microl/10s) injection of microbubbles on both types of curves were investigated. Sensitivities of both methods for assessing effects of antiangiogenic treatment (SU11248) were examined. Correlative histological analysis was performed for vessel-density. Mann-Whitney test was used for statistical analysis. Microbubble injection rates significantly influenced upslope, time-to-peak and peak enhancement of conventional TI curves (p<0.05) but had almost no impact on maximum enhancement of MIOT curves (representing relative blood volume). Additionally, maximum enhancement of MIOT curves captured antiangiogenic therapy effects more reliably and earlier (already after 1 day of therapy; p<0.05) than peak enhancement of TI curves. Immunohistochemistry validated the significantly (p<0.01) lower vessel densities in treated tumors and high correlation (R(2)=0.95) between vessel-density and maximum enhancement of MIOT curves was observed. In conclusion, MIOT is less susceptible to variations of the injection's speed. It enables to assess changes of the relative blood volume earlier and with lower standard deviations than conventional TI curves. It can easily be translated into clinical practice and thus may provide a promising tool for cancer therapy monitoring.

MMP Inhibition Blocks Fibroblast-dependent Skin Cancer Invasion, Reduces Vascularization and Alters VEGF-A and PDGF-BB Expression

Anticancer Research. Mar, 2010  |  Pubmed ID: 20392987

Tumor invasion requires intense interactions with stromal cells and a profound extracellular matrix remodelling by matrix metalloproteinases (MMPs). Here, we assessed the specific contribution of fibroblasts to tumor invasion, MMPs, tissue inhibitors of MMPs and angiogenesis-related cytokine expression in organotypic cultures of highly malignant HaCaT-ras A-5RT3 cells, with and without MMP inhibition. Collagen degradation, the hallmark of tumor invasion, was dependent on fibroblasts and active MMP-2. Additionally, MMP blockade down-regulated VEGF-A and up-regulated PDGF-BB. These results were paralleled in xenotransplants in vivo, demonstrating strong inhibitory effects of MMP blockade on tumor invasion and vascularization, as shown by the almost complete absence of VEGF-A and MMP-14 and by the decrease in relative blood volume. MMP blockade also increased the fraction of mature vessels, as demonstrated by an increased mean tumor vessel diameter and a higher ratio of Ng2-positive vessels. Thus, this study highlights the importance of targeting the tumor stroma to defeat cancer.

Real-time MR Navigation and Localization of an Intravascular Catheter with Ferromagnetic Components

Magma (New York, N.Y.). Jun, 2010  |  Pubmed ID: 20495846

To develop an intravascular catheter with ferromagnetic components that is navigated with MR gradient forces and imaged with dedicated MR sequences in real time.

Anti-CD4-targeted Gold Nanoparticles Induce Specific Contrast Enhancement of Peripheral Lymph Nodes in X-ray Computed Tomography of Live Mice

Nano Letters. Jul, 2010  |  Pubmed ID: 20496900

Antibody-conjugated gold nanoparticles have been applied as a biologically targeted contrast agent in live mice for one of the most widely used medical imaging methods, X-ray computed tomography. Such nanoprobes directed toward the CD4 receptor lead to distinctly enhanced X-ray contrast of peripheral lymph nodes. This study demonstrates the general feasibility of biologically specific X-ray imaging in living animals and discusses basic requirements for the use of nanoparticles as a targeted X-ray contrast agent.

A Long Arm for Ultrasound: a Combined Robotic Focused Ultrasound Setup for Magnetic Resonance-guided Focused Ultrasound Surgery

Medical Physics. May, 2010  |  Pubmed ID: 20527572

Focused ultrasound surgery (FUS) is a highly precise noninvasive procedure to ablate pathogenic tissue. FUS therapy is often combined with magnetic resonance (MR) imaging as MR imaging offers excellent target identification and allows for continuous monitoring of FUS induced temperature changes. As the dimensions of the ultrasound (US) focus are typically much smaller than the targeted volume, multiple sonications and focus repositioning are interleaved to scan the focus over the target volume. Focal scanning can be achieved electronically by using phased-array US transducers or mechanically by using dedicated mechanical actuators. In this study, the authors propose and evaluate the precision of a combined robotic FUS setup to overcome some of the limitations of the existing MRgFUS systems. Such systems are typically integrated into the patient table of the MR scanner and thus only provide an application of the US wave within a limited spatial range from below the patient.

Drug-induced Vessel Remodeling in Bone Metastases As Assessed by Dynamic Contrast Enhanced Magnetic Resonance Imaging and Vessel Size Imaging: a Longitudinal in Vivo Study

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Jun, 2010  |  Pubmed ID: 20530698

The aim of this study was to assess the antiangiogenic treatment effects of zoledronic acid (ZA) and sunitinib malate (SM) noninvasively in experimental breast cancer bone metastases by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging.

Active Microcoil Tracking in the Lungs Using a Semisolid Rubber As Signal Source

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jul, 2010  |  Pubmed ID: 20572154

A new method to localize and track medical devices in air-filled body cavities is proposed that uses active microcoils with a semisolid filling. In air spaces, e.g., the lung, microcoils require an independent signal source, which should be made of a biocompatible, solid and sterilizable material with a long shelf time. In a measurement of the T(1) and T*(2) and the relative spin density of several semisolid materials, latex was identified as a suitable material from which a prototype catheter was constructed with a microcoil at its tip. In a dual-echo tracking pulse sequence, the very short T*(2) of the rubber material allowed suppressing the background signal from surrounding tissue with a subtraction technique and additional dephasing gradients. With a roadmapping reconstruction, the microcoil's trajectory could be visualized on a previously acquired reference image set with a tracking rate of up to 60 Hz at a spatial resolution of better than 2mm. In a real-time tracking implementation, an image update rate of 4 Hz was achieved by combining the tracking with a fast real-time imaging sequence. Both methods were successfully applied in vivo to track the catheter in the lung of a pig.

[Quantitative MR-Spectroscopy: Implementation and Quality Assurance on a Clinical MR-scanner]

Zeitschrift Für Medizinische Physik. 2010  |  Pubmed ID: 20663651

The aim of this study was the implementation of quantitative MR-Spectroscopy with external reference signals on a Philips Gyroscan Intera 1,5 T MR-Scanner for routine clinical use. We established measurements for quality assurance of the used phantoms and methods. In detail we analyzed the dependence of the signal on concentration and volume as well as on the local variation within the coil and the impact of these factors on quantification. Furthermore we established measurements for routine constancy checks. The method as well as the software for concentration calculation was checked by an in vitro measurement. In a blinded measurement the concentrations of NAA, Cho and Kr in the PTB reference phantom 10614mM were determined correctly within their error limits.

Novel Spherical Phantoms for Q-ball Imaging Under in Vivo Conditions

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jan, 2011  |  Pubmed ID: 20740652

For the validation of complex diffusion imaging techniques like q-ball imaging that aim to resolve multiple fiber directions, appropriate phantoms are highly desirable. However, previous q-ball imaging phantoms had diffusion anisotropies well below those of in vivo white matter. In this work, fiber phantoms of well-defined geometry are presented. The fibers are wound on a spherical spindle yielding high packing densities and consequently high diffusion anisotropies (fractional anisotropy 0.93 ± 0.02 at b = 500 s/mm(2)). Phantoms with 90° and 45° crossing angle were constructed both with two crossing types. In the "stacked" crossing, two fiber strings were wound consecutively to simulate two touching fibers, in the "interleaved" crossing, fibers were wound alternately. The stacked crossing allows the alteration of partial volumes, whereas the interleaved crossing provides constant partial volumes, allowing e.g. the easy alteration of the SNR by varying the slice thickness. Exemplary q-ball imaging validation measurements using different b-values and slice thicknesses are presented.

Sorafenib Tosylate and Paclitaxel Induce Anti-angiogenic, Anti-tumour and Anti-resorptive Effects in Experimental Breast Cancer Bone Metastases

European Journal of Cancer (Oxford, England : 1990). Jan, 2011  |  Pubmed ID: 20863686

In this study we investigated sorafenib tosylate and paclitaxel as single and combination therapies regarding their effects on tumour growth and vasculature as well as their potency to inhibit osteolysis in experimental breast cancer bone metastases.

Compatibility Between 3T 1H SV-MRS Data and Automatic Brain Tumour Diagnosis Support Systems Based on Databases of 1.5T 1H SV-MRS Spectra

Magma (New York, N.Y.). Feb, 2011  |  Pubmed ID: 21249420

This study demonstrates that 3T SV-MRS data can be used with the currently available automatic brain tumour diagnostic classifiers which were trained on databases of 1.5T spectra. This will allow the existing large databases of 1.5T MRS data to be used for diagnostic classification of 3T spectra, and perhaps also the combination of 1.5T and 3T databases.

First Multimodal Embolization Particles Visible on X-ray/computed Tomography and Magnetic Resonance Imaging

Investigative Radiology. Mar, 2011  |  Pubmed ID: 21263332

Embolization therapy is gaining importance in the treatment of malignant lesions, and even more in benign lesions. Current embolization materials are not visible in imaging modalities. However, it is assumed that directly visible embolization material may provide several advantages over current embolization agents, ranging from particle shunt and reflux prevention to improved therapy control and follow-up assessment. X-ray- as well as magnetic resonance imaging (MRI)-visible embolization materials have been demonstrated in experiments. In this study, we present an embolization material with the property of being visible in more than one imaging modality, namely MRI and x-ray/computed tomography (CT). Characterization and testing of the substance in animal models was performed.

Optically Detunable, Inductively Coupled Coil for Self-gating in Small Animal Magnetic Resonance Imaging

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Mar, 2011  |  Pubmed ID: 21337415

An inductively coupled coil concept is presented, which improves the compensation of physiological motion by the self-gating (SG) technique. The animal is positioned in a conventional volume coil encompassing the whole animal. A small, resonant surface coil (SG-coil) is placed on the thorax so that its sensitive region includes the heart. Via inductive coupling the SG-coil amplifies selectively the MR signal of the beating heart. With an optical detuning mechanism, this coupling can be switched off during acquisition of the MR image information, whereas it is active during SG data sampling to provide the physiological information. In vivo experiments on a mouse show an amplification of the SG signal by at least 40%.

Outer Volume Suppression in Steady State Sequences (OVSuSS) for Percutaneous Interventions

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Jul, 2011  |  Pubmed ID: 21337422

Magnetic resonance-guided percutaneous interventions with needles require fast pulse sequences with acquisition times less than 1 s to image the needle trajectory within moving organs. To guide the movement of a rigid instrument with high sampling rate, an magnetic resonance imaging method was developed that reduces the acquisition time down to a few hundred milliseconds by restricting the field of view to a small stripe around the instrument trajectory. To maintain the dynamic steady state, saturation pulses for outer volume suppression were inserted into additional repetition time-intervals. These saturation intervals were combined with three sequence variants: a spoiled gradient echo sequence, an echo-shifted steady state free precession and a balanced steady state free precession sequence. The magnetization dynamics were analyzed by means of numerical optimized simulations. Results were compared with phantom experiments and an average signal-to-suppression-ratio of 15.5 could be achieved. With a field of view reduction of up to 12.5% an update rate of six images per second could be achieved. Finally, animal experiments demonstrated the fast and reliable needle tip visualization during percutaneous magnetic resonance-guided interventions with the help of a robotic assistance system.

Cilengitide Inhibits Progression of Experimental Breast Cancer Bone Metastases As Imaged Noninvasively Using VCT, MRI and DCE-MRI in a Longitudinal in Vivo Study

International Journal of Cancer. Journal International Du Cancer. May, 2011  |  Pubmed ID: 20648558

The aim of this study was to investigate the effect of inhibiting αvβ(3)/α(v) β(5) integrins by cilengitide in experimentally induced breast cancer bone metastases using noninvasive imaging techniques. For this purpose, nude rats bearing established breast cancer bone metastases were treated with cilengitide, a small molecule inhibitor of αvβ(3) and αvβ(5) integrins (75 mg/kg, five days per week; n = 12 rats) and compared to vehicle-treated control rats (n = 12). In a longitudinal study, conventional magnetic resonance imaging (MRI) and flat panel volumetric computed tomography were used to assess the volume of the soft tissue tumor and osteolysis, respectively, and dynamic contrast-enhanced (DCE-) MRI was performed to determine functional parameters of the tumor vasculature reflecting blood volume and blood vessel permeability. In rats treated with cilengitide, VCT and MRI showed that osteolytic lesions and the respective bone metastatic soft tissue tumors progressed more slowly than in vehicle-treated controls. DCE-MRI indicated a decrease in blood volume and an increase in vessel permeability and immunohistology revealed increased numbers of immature vessels in cilengitide-treated rats compared to vehicle controls. In conclusion, treatment of experimental breast cancer bone metastases with cilengitide resulted in pronounced antiresorptive and antitumor effects, suggesting that αvβ(3)/αvβ(5) inhibition may be a promising therapeutic approach for bone metastases.

The Potential of Relaxation-weighted Sodium Magnetic Resonance Imaging As Demonstrated on Brain Tumors

Investigative Radiology. Sep, 2011  |  Pubmed ID: 21577129

: Total tissue sodium (Na) content is associated with the viability of cells and can be assessed by Na magnetic resonance imaging. However, the resulting total sodium signal (NaT) represents a volume-weighted average of different sodium compartments assigned to the intra- and extracellular space. In addition to the spin-density weighted contrast of NaT imaging, relaxation-weighted (NaR) sequences were applied. The aim of this study was to evaluate the potential of NaR imaging for tissue characterization and putative additional benefits to NaT imaging.

Cilengitide Inhibits Metastatic Bone Colonization in a Nude Rat Model

Oncology Reports. Oct, 2011  |  Pubmed ID: 21725616

Integrins αvβ3 and αvβ5 are considered to play an important role in the pathogenesis of breast cancer bone metastases. This study investigates the effects of the αvβ3/αvβ5 integrin-specific inhibitor cilengitide during early metastatic bone colonization. The impact of cilengitide on the migration, invasion and proliferation of MDA-MB-231 human breast carcinoma cells as well as on bone resorption by osteoclasts was investigated in vitro. For in vivo experiments, nude rats were treated with cilengitide for 30 days starting one day after site-specific tumor cell inoculation in the hind leg, and the course of metastatic changes in bone was followed using flat-panel volumetric computed tomography (VCT) and magnetic resonance imaging (MRI). Vascular changes in bone metastases were investigated using dynamic contrast-enhanced (DCE-) MRI-derived parameters amplitude A and exchange rate coefficient kep. In vitro, cilengitide treatment resulted in a decrease in proliferation, migration and invasion of MDA-MB-231 cells, as well as of osteoclast activity. In vivo, the development of bone metastasis in the hind leg of rats was not prevented by adjuvant cilengitide treatment, but cilengitide reduced the volumes of osteolytic lesions and respective soft tissue tumors of developing bone metastases as assessed with VCT and MRI, respectively. DCE-MRI revealed significant changes in the A and kep parameters including decreased relative blood volume and increased vessel permeability after cilengitide treatment indicating vessel remodeling. In conclusion, during early pathogenic processes of bone colonization, cilengitide treatment exerted effects on tumor cells, osteoclasts and vasculature reducing the skeletal lesion size of experimental skeletal metastases.

3 Tesla Sodium Inversion Recovery Magnetic Resonance Imaging Allows for Improved Visualization of Intracellular Sodium Content Changes in Muscular Channelopathies

Investigative Radiology. Dec, 2011  |  Pubmed ID: 21750464

To implement different sodium (²³Na)-magnetic resonance imaging (MRI) contrasts at 3 Tesla and to evaluate if a weighting toward intracellular sodium can be achieved, using 2 rare muscular channelopathies as model diseases.

Effects of Static Magnetic Fields on Cognition, Vital Signs, and Sensory Perception: a Meta-analysis

Journal of Magnetic Resonance Imaging : JMRI. Oct, 2011  |  Pubmed ID: 21751291

To evaluate whether cognitive processes, sensory perception, and vital signs might be influenced by static magnetic fields in magnetic resonance imaging (MRI), which could pose a risk for health personnel and patients, we conducted a meta-analysis of studies that examined effects of static magnetic fields. Studies covering the time from 1992 to 2007 were selected. Cohen's d effects sizes were used and combined in different categories of neuropsychology (reaction time, visual processing, eye-hand coordination, and working memory). Additionally, effects of static magnetic fields on sensory perception and vital signs were analyzed. In the category "neuropsychology," only effects on the visual system were homogeneous, showing a statistically significant impairment as a result of exposure to static magnetic fields (d = -0.415). Vital signs were not affected and effects on sensory perceptions included an increase of dizziness and vertigo, primarily caused by movement during static magnetic field gradient exposures. The number of studies dealing with this topic is very small and the experimental set-up of some of the analyzed studies makes it difficult to accurately determine the effects of static magnetic fields by themselves, excluding nonspecific factors. The implications of these results for MRI lead to suggestions for improvement in research designs.

MR Safety: Simultaneous B0, DΦ/dt, and DB/dt Measurements on MR-workers Up to 7 T

Magma (New York, N.Y.). Dec, 2011  |  Pubmed ID: 21755466

The EU directive on safety requirements (2004/40/EC) limits the exposure to time varying magnetic fields to dB /dt=200 mT/s. This action value is not clearly defined as it considers only the temporal change of the magnitude of B. Thus, only the translational motion in the magnet's fringe field is considered and rotations are neglected.

Determination of the Defining Boundary in Nuclear Magnetic Resonance Diffusion Experiments

Physical Review Letters. Jul, 2011  |  Pubmed ID: 21867047

While nuclear magnetic resonance diffusion experiments are widely used to resolve structures confining the diffusion process, it has been elusive whether they can exactly reveal these structures. This question is closely related to x-ray scattering and to Kac's "hear the drum" problem. Although the shape of the drum is not "hearable," we show that the confining boundary of closed pores can indeed be detected using modified Stejskal-Tanner magnetic field gradients that preserve the phase information and enable imaging of the average pore in a porous medium with a largely increased signal-to-noise ratio.

Theranostic CRGD-BioShuttle Constructs Containing Temozolomide- and Cy7 For NIR-Imaging and Therapy

Theranostics. 2011  |  Pubmed ID: 22211144

Innovative and personalized therapeutic approaches result from the identification and control of individual aberrantly expressed genes at the transcriptional and post-transcriptional level. Therefore, it is of high interest to establish diagnostic, therapeutic and theranostic strategies at these levels. In the present study, we used the Diels-Alder Reaction with inverse electron demand (DAR(inv)) click chemistry to prepare a series of cyclic RGD-BioShuttle constructs. These constructs carry the near-infrared (NIR) imaging agent Cy7 and the chemotherapeutic agent temozolomide (TMZ). We evaluated their uptake by and their efficacy against integrin α(v)β(3)-expressing MCF7 human breast carcinoma cells. In addition, using a mouse phantom, we analyzed the suitability of this targeted theranostic agent for NIR optical imaging. We observed that the cyclic RGD-based carriers containing TMZ and/or Cy7 were effectively taken up by α(v)β(3)-expressing cells, that they were more effective than free TMZ in inducing cell death, and that they could be quantitatively visualized using NIR fluorescence imaging. Therefore, these targeted theranostic agents are considered to be highly suitable systems for improving disease diagnosis and therapy.

Improved Visualization of Delayed Perfusion in Lung MRI

European Journal of Radiology. Jan, 2011  |  Pubmed ID: 19713064

The investigation of pulmonary perfusion by three-dimensional (3D) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was proposed recently. Subtraction images are generated for clinical evaluation, but temporal information is lost and perfusion defects might therefore be masked in this process. The aim of this study is to demonstrate a simple analysis strategy and classification for 3D-DCE-MRI perfusion datasets in the lung without omitting the temporal information.

A Novel PET Tracer for the Imaging of αvβ3 and αvβ5 Integrins in Experimental Breast Cancer Bone Metastases

Contrast Media & Molecular Imaging. Nov-Dec, 2011  |  Pubmed ID: 22162137

The aim of this study was the evaluation of (68)Ga-DOTA-E-[c(RGDfK)](2) as a novel PET tracer to image αvβ3 and αvβ5 integrins. For this purpose, DOTA-E-[c(RGDfK)](2) was labeled with (68)Ga, which was obtained from a (68)Ge/(68)Ga generator, purified by solid-phase extraction and the radiochemical purity analyzed by radio-RP-HPLC. (68) Ga-DOTA-E-[c(RGDfK)](2) was obtained reproducibly in radiochemical yields of 60 ± 6% and with an excellent radiochemical purity of >99%. In nude rats bearing bone metastases after injection of MDA-MB-231 human breast cancer cells, biodistribution studies were performed to evaluate the accumulation of the radiotracer in selected organs, blood and bone metastases 0.5, 1, 2 and 3 h post injection. A rapid uptake into the bone metastases and rapid blood clearance was observed, resulting in tumor-blood ratios of up to 26.6 (3 h post injection) and tumor-muscle ratios of up to 7.9 (3 h post injection). A blocking experiment with coinjected αvβ3/αvβ5 antagonist showed the tumor uptake to be receptor-specific. In an initial in vivo micro PET evaluation of the tracer using the same animal model, the bone metastasis was clearly visualized. These results suggest that (68)Ga-DOTA-E-[c(RGDfK)](2) is a promising PET tracer suitable for the imaging of αvβ3 and αvβ5 integrins in bone metastases. This novel PET tracer should be further evaluated concerning its usefulness for early detection of bone metastases and monitoring treatment response of these lesions.

Advanced Fit of the Diffusion Kurtosis Tensor by Directional Weighting and Regularization

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. May, 2012  |  Pubmed ID: 22189630

The diffusional kurtosis is an indicator for diffusion restrictions in biological tissue. It is observed experimentally that the kurtosis is largest for directions perpendicular to the fiber direction in white matter. The directional dependence of the kurtosis can be described by the diffusion kurtosis tensor. Since the intention of diffusion kurtosis imaging is to detect diffusion restrictions, the fit of the kurtosis tensor should be dominated by directions perpendicular to the fibers. In this work, it is shown that the basic approach, which is solving the occurring linear system by a pseudoinverse matrix, may completely fail in this regard if the diffusion is highly anisotropic. This problem is solved by adapting the weights of the fit--and thus emphasizing directions of restricted water motion--using a direct fit of the kurtosis tensor to the measured kurtosis values. Moreover, due to its large number of degrees of freedom, the kurtosis tensor can assume complicated shapes resulting in a fit which is sensitive to noise. This article demonstrates that the quality of the kurtosis tensor calculation can be further improved if the fit is regularized by suppressing too large and too small kurtosis tensor values and thus restricting the possible tensor shapes.

Monitoring Molecular, Functional and Morphologic Aspects of Bone Metastases Using Non-invasive Imaging

Current Pharmaceutical Biotechnology. Mar, 2012  |  Pubmed ID: 22214500

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

Synthesis and in Vitro Evaluation of 68Ga-DOTA-4-FBn-TN14003, a Novel Tracer for the Imaging of CXCR4 Expression

Bioorganic & Medicinal Chemistry. Feb, 2012  |  Pubmed ID: 22264762

The expression of the chemokine receptor CXCR4 in tumors is associated with tumor aggressiveness and poor prognosis for the patient and contributes to metastatic seeding. Therefore it is of high interest to find a specific PET tracer for the imaging of CXCR4 expression in tumors. The aim of this study was the synthesis, (68)Ga labeling and first evaluation of DOTA-4-FBn-TN14003 as a potential PET tracer for this purpose. DOTA-4-FBn-TN14003 was synthesized using solid phase peptide synthesis and radiolabeling of this versatile precursor was performed with (68)Ga, which was obtained from a (68)Ge/(68)Ga generator. (68)Ga-DOTA-4-FBn-TN14003 was reproducibly obtained in isolated radiochemical yields of 72.5±4.9% with an excellent radiochemical purity of >99.5%. Specific activities of up to 29.8±3.1 GBq/μmol were achieved. In competition binding assays with SDF-1α, human T cell lymphoma Jurkat cells expressed high levels of CXCR4 whereas human breast cancer MDA-MB-231 cells expressed significantly lower levels of this chemokine receptor. The inhibition constants (IC(50)) of Ga-DOTA-4-FBn-TN14003 and 4-FBn-TN14003 to CXCR4 were determined in a competition assay against (125)I-SDF-1α using Jurkat as well as MDA-MB-231 cells. The IC(50) values of Ga-DOTA-4-FBn-TN14003 (1.99±0.31 nM) and 4-FBn-TN14003 (4.07±1.00 nM) proved to be comparable, indicating negligible influence of the metal complex. These results suggest (68)Ga-DOTA-4-FBn-TN14003 as a promising agent for the imaging of CXCR4 expression in tumors and metastases.

Lung Ventilation- and Perfusion-weighted Fourier Decomposition Magnetic Resonance Imaging: In Vivo Validation with Hyperpolarized (3) He and Dynamic Contrast-enhanced MRI

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Mar, 2012  |  Pubmed ID: 22392633

The purpose of this work was to validate ventilation-weighted (VW) and perfusion-weighted (QW) Fourier decomposition (FD) magnetic resonance imaging (MRI) with hyperpolarized (3) He MRI and dynamic contrast-enhanced perfusion (DCE) MRI in a controlled animal experiment. Three healthy pigs were studied on 1.5-T MR scanner. For FD MRI, the VW and QW images were obtained by postprocessing of time-resolved lung image sets. DCE acquisitions were performed immediately after contrast agent injection. (3) He MRI data were acquired following the administration of hyperpolarized helium and nitrogen mixture. After baseline MR scans, pulmonary embolism was artificially produced. FD MRI and DCE MRI perfusion measurements were repeated. Subsequently, atelectasis and air trapping were induced, which followed with FD MRI and (3) He MRI ventilation measurements. Distributions of signal intensities in healthy and pathologic lung tissue were compared by statistical analysis. Images acquired using FD, (3) He, and DCE MRI in all animals before the interventional procedure showed homogeneous ventilation and perfusion. Functional defects were detected by all MRI techniques at identical anatomical locations. Signal intensity in VW and QW images was significantly lower in pathological than in healthy lung parenchyma. The study has shown usefulness of FD MRI as an alternative, noninvasive, and easily implementable technique for the assessment of acute changes in lung function. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

Two Eyes See More Than One: Double Echo Stereoscopic MRA for Rapid 3D Visualization of Vascular Structures

Magma (New York, N.Y.). Apr, 2012  |  Pubmed ID: 22476546

OBJECT: A three-dimensional (3D) visualization of the target region during intravascular interventions in real-time is challenging since the acquisition of a time-consuming 3D dataset is required. In this work, a novel stereoscopic double echo sequence for achieving 3D depth perception by sampling only two oblique projection images is presented. MATERIALS AND METHODS: A double echo (DE) FLASH pulse sequence was developed to acquire continuously stereoscopic image pairs of the vascular target anatomy. Stereo image data were displayed on a stereoscopic 3D LCD monitor in real time after image reconstruction. Phantom experiments followed by a depth perception test were performed to assess the usability of the stereo image pairs for 3D visualization. In an animal experiment the sequence was tested in vivo and was compared with a slower interleaved (IL) sequence variant. RESULTS: In the phantom experiments an SNR difference of 6 % between left and right image was found which did not influence the depth perception. The DE acquisition was superior to the IL sequence (SNR(DE) = 10.3, 2.3 images/s over SNR(IL) = 7.1, 1.7 images/s), and during contrast enhancement the abdominal arterial vasculature was clearly perceived as a 3D structure. CONCLUSION: A novel stereoscopic DE pulse sequence can be utilized for the fast 3D stereoscopic visualization of vascular structures in real-time.

Quantitative Contrast-enhanced Ultrasound for Imaging Antiangiogenic Treatment Response in Experimental Osteolytic Breast Cancer Bone Metastases

Investigative Radiology. Jul, 2012  |  Pubmed ID: 22659593

The aim of this study was to investigate the feasibility of using contrast-enhanced ultrasound (CEUS) in experimental breast cancer bone metastases and its utilization for assessment of early antiangiogenic treatment response in these lesions.

A Cross-over Study of Effects on the Hypothalamus-pituitary-adrenal (HPA) Axis and the Sympathoadrenergic System in Magnetic Field Strength Exposure from 0 to 7 T

Stress (Amsterdam, Netherlands). Aug, 2012  |  Pubmed ID: 22775799

The concept of stress is relevant to magnetic resonance imaging (MRI) examination in various ways. First, levels of stress to staff and patients have not been quantified in ultra-high magnetic fields. Second, research is increasingly interested in experimentally defining regional brain activity during stress. It is therefore important to know whether exposure to the ultra-high static magnetic fields per se might also lead to neurohormonal responses in the hypothalamus-pituitary-adrenal axis and the sympathoadrenal systems. In the present blinded case cross-over study with 41 healthy participants, we measured cortisol not only before and after but also during static magnetic field exposure in MRI scanners. Measures of catecholamines before and after exposure were also part of the study protocol. Using three different field strengths (1.5, 3 and 7 T) and a mock scanner (0 T), we examined whether not only the MRI procedure but also the static magnetic field per se has an influence on the neuroendocrine responses. We found no significant differences in the course of cortisol or catecholamine concentrations between the different static magnetic fields. Our study suggests that the results of MRI studies using stress-paradigms are not influenced by the static magnetic field itself.

BioShuttle Mobility in Living Cells Studied with High-Resolution FCS & CLSM Methodologies

International Journal of Medical Sciences. 2012  |  Pubmed ID: 22811608

With the increase in molecular diagnostics and patient-specific therapeutic approaches, the delivery and targeting of imaging molecules and pharmacologically active agents gain increasing importance. The ideal delivery system does not exist yet. The realization of two features is indispensable: first, a locally high concentration of target-specific diagnostic and therapeutic molecules; second, the broad development of effective and safe carrier systems. Here we characterize the transport properties of the peptide-based BioShuttle transporter using FFM and CLSM methods. The modular design of BioShuttle-based formulations results in a multi-faceted field of applications, also as a theranostic tool.

Coaxial Waveguide MRI

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Apr, 2012  |  Pubmed ID: 22021117

As ultrahigh-field MR imaging systems suffer from the standing wave problems of conventional coil designs, the use of antenna systems that generate travelling waves was suggested. As a modification to the original approach, we propose the use of a coaxial waveguide configuration with interrupted inner conductor. This concept can focus the radiofrequency energy to the desired imaging region in the human body and can operate at different Larmor frequencies without hardware modifications, as it is not limited by a lower cut-off frequency. We assessed the potential of the method with a hardware prototype setup that was loaded with a tissue equivalent phantom and operated with imaging areas of different size. Signal and flip angle distributions within the phantom were analyzed, and imaging at different Larmor frequencies was performed. Results were compared to a finite difference time domain simulation of the setup that additionally provides information on the spatial distribution of the specific absorption rate load. Furthermore, simulation results with a human model (virtual family) are presented. It was found that the proposed method can be used for MRI at multiple frequencies, achieving transmission efficiencies similar to other travelling wave approaches but still suffers from several limitations due to the used mode of wave propagation.

Velocity Navigator for Motion Compensated Thermometry

Magma (New York, N.Y.). Feb, 2012  |  Pubmed ID: 21373916

Proton resonance frequency shift thermometry is sensitive to breathing motion that leads to incorrect phase differences. In this work, a novel velocity-sensitive navigator technique for triggering MR thermometry image acquisition is presented.