In vivo visualization of mesoscopic anatomy of healthy and pathological lymph nodes using 7T MRI: a feasibility study.

PURPOSE: To evaluate whether inguinal lymph nodes (LNs) may be visualized in vivo using 7T magnetic resonance imaging (MRI) at high spatial resolution. MATERIALS AND METHODS: Twelve healthy controls and six patients with LN metastasis of melanoma were included. Examinations were performed using a 7T MRI and a transmit/receive loop coil. The protocol included a B0 -map, B1 -map, and T1 -weighted-3D-fast low-angle shot (FLASH), T1 w-Dixon-volumetric interpolated breath-hold examination (VIBE) and T2 w sequences lasting 34.4 ± 0.5 minutes. Signal- and contrast-to-noise of LNs, artery, muscle, and fat were quantified in controls. Metastatic features of LNs (hypervascularization, lymph vessels, fat hilus sign, tumor bulk, number of metastases, and size) were classified in patients. RESULTS: Mesoscopic LN architecture such as central blood vessels and peripheral lymph vessels were observed in healthy controls with 0.5 mm(3) isotropic resolution for T1 w and 0.2 × 0.2 × 2 mm(3) for T2 w sequences. Mean signal-to-noise using 3D FLASH, Dixon VIBE and T2 TSE of healthy LN (27.2 ± 7.5, 35.3 ± 11.9, 31.7 ± 11.1), muscle (17.6 ± 4.6, 31.5 ± 9.3, 7.3 ± 5.4), artery (37.7 ± 5.9, 42.7 ± 19.7, 3.7 ± 3.9), and saturated fat (3.7 ± 0.9, 5.4 ± 1.9, 9.3 ± 5.2) and mean contrast-to-noise LN/fat (24.4 ± 6.7, 39.6 ± 11.1, 23.3 ± 6.1) were adequate. In patients, multiple signs of metastasis could be clearly visualized. CONCLUSION: We present a protocol with which inguinal LNs and their mesoscopic anatomy may be visualized in vivo using 7T MRI.

In vivo 35Cl MR imaging in humans: a feasibility study.

PURPOSE: To implement chlorine 35 ((35)Cl) magnetic resonance (MR) at a 7-T whole-body MR system and evaluate its feasibility for imaging humans. MATERIALS AND METHODS: All examinations were performed with ethical review board approval; written informed consent was obtained from all volunteers. Seven examinations each of brain and muscle in healthy volunteers and four examinations of patients were performed. Two patients with histologically confirmed glioblastoma multiforme underwent brain imaging. (35)Cl MR and (35)Cl inversion-recovery (IR) MR were performed. Two patients with genetically confirmed hypokalemic periodic paralysis underwent calf muscle imaging. Seven multiecho sequences (acquisition time, 5 minutes; voxel dimension, 11 mm(3)) were applied to determine transverse relaxation time as affected by magnetic field heterogeneity (T2*) and chlorine concentration. (35)Cl and sodium 23 ((23)Na) MR were conducted with a 7-T whole-body MR system. (35)Cl longitudinal relaxation time (T1) and T2* of healthy human brain and muscle were determined with a three-dimensional density-adapted-projection reconstruction technique to achieve short echo times and high signal-to-noise ratio (SNR) efficiency. A nonlinear least squares routine and mono- (T1) and biexponential (T2*) models were used for curve fitting. RESULTS: Phantom imaging revealed 15-fold lower SNR and much shorter relaxation times for (35)Cl than (23)Na. In vivo T2* was biexponential and extremely short. Monoexponential fits of T1 revealed 9.2 and 4.0 milliseconds ± 0.7 (standard deviation) for brain and muscle, respectively. In glioblastoma tissue, increased Cl(-) concentrations and increased Cl(-) IR signal intensities were detected. Voxel dimension and acquisition time, respectively, were 6 mm(3) and 9 minutes 45 seconds ((35)Cl MR) and 10 mm(3) and 10 minutes ((35)Cl IR MR). In patients with hypokalemic periodic paralysis versus healthy volunteers, Cl(-) and Na(+) concentrations were increased. Cl(-) concentration of muscle could be determined (voxel size, 11 mm(3); total acquisition time, 35 minutes). CONCLUSION: MR at 7 T enables in vivo imaging of (35)Cl in human brain and muscle in clinically feasible acquisition times (10-35 minutes) and voxel volumes (0.2-1.3 cm(3)). Pathophysiological changes of Cl(-) homeostasis due to cancer or muscular ion channel disease can be visualized.

Iterative 3D projection reconstruction of (23) Na data with an (1) H MRI constraint.

PURPOSE: To increase the signal-to-noise ratio (SNR) and to reduce artifacts in non-proton magnetic resonance imaging (MRI) by incorporation of a priori information from (1) H MR data in an iterative reconstruction. METHODS: An iterative reconstruction algorithm for 3D projection reconstruction (3DPR) is presented that combines prior anatomical knowledge and image sparsity under a total variation (TV) constraint. A binary mask (BM) is used as an anatomical constraint to penalize non-zero signal intensities outside the object. The BM&TV method is evaluated in simulations and in MR measurements in volunteers. RESULTS: In simulated BM&TV brain data, the artifact level was reduced by 20% while structures were well preserved compared to gridding. SNR maps showed a spatially dependent SNR gain over gridding reconstruction, which was up to 100% for simulated data. Undersampled 3DPR (23) Na MRI of the human brain revealed an SNR increase of 29 ± 7%. Small anatomical structures were reproduced with a mean contrast loss of 14%, whereas in TV-regularized iterative reconstructions a loss of 66% was found. CONCLUSION: The BM&TV algorithm allows reconstructing images with increased SNR and reduced artifact level compared to gridding and performs superior to an iterative reconstruction using an unspecific TV constraint only.

A peptide & peptide nucleic acid synthesis technology for transporter molecules and theranostics--the SPPS.

Advances in imaging diagnostics using magnetic resonance tomography (MRT), positron emission tomography (PET) and fluorescence imaging including near infrared (NIR) imaging methods are facilitated by constant improvement of the concepts of peptide synthesis. Feasible patient-specific theranostic platforms in the personalized medicine are particularly dependent on efficient and clinically applicable peptide constructs. The role of peptides in the interrelations between the structure and function of proteins is widely investigated, especially by using computer-assisted methods. Nowadays the solid phase synthesis (SPPS) chemistry emerges as a key technology and is considered as a promising methodology to design peptides for the investigation of molecular pharmacological processes at the transcriptional level. SPPS syntheses could be carried out in core facilities producing peptides for large-scale scientific implementations as presented here.

An MR-compatible stereoscopic in-room 3D display for MR-guided interventions.

BACKGROUND AND METHODS: A commercial three-dimensional (3D) monitor was modified for use inside the scanner room to provide stereoscopic real-time visualization during magnetic resonance (MR)-guided interventions, and tested in a catheter-tracking phantom experiment at 1.5 T. Brightness, uniformity, radio frequency (RF) emissions and MR image interferences were measured. RESULTS AND DISCUSSION: Due to modifications, the center luminance of the 3D monitor was reduced by 14%, and the addition of a Faraday shield further reduced the remaining luminance by 31%. RF emissions could be effectively shielded; only a minor signal-to-noise ratio (SNR) decrease of 4.6% was observed during imaging. During the tracking experiment, the 3D orientation of the catheter and vessel structures in the phantom could be visualized stereoscopically.

Direct (17)O MRI with partial volume correction: first experiences in a glioblastoma patient.

OBJECT: In tumor cells the energy production is shifted from aerobic to anaerobic metabolization of glucose, which makes the cerebral metabolic rate of oxygen consumption (CMRO2) a diagnostic parameter for tissue viability. Direct oxygen-17 ((17)O) MRI during inhalation of (17)O gas allows for a non-invasive determination of the CMRO2. However, the low spatial resolution and the fast transverse relaxation of (17)O lead to partial volume effects that severely bias the quantification of signal intensities. The aim of this work was to determine the CMRO2 in a tumor patient by (17)O MRI in combination with a partial volume correction (PVC) scheme. MATERIALS AND METHODS: Direct (17)O MRI was performed in a glioblastoma patient (F, 51 years) prior to surgery at 7 T. The 'geometric transfer matrix' algorithm for volume of interest based PVC was adapted to (17)O MRI to recover the true signal intensities. We determined the CMRO2 values of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and the tumor areas of the contrast enhancing rim (CE), the necrotic center (NE), and the perifocal edema (PE) using a three-phase metabolic model. RESULTS: Large differences in the signal increase during (17)O2 inhalation were obtained ranging from less than 2% in the tumor center up to more than 20% in GM areas. After PVC of the signal time curves, we determined CMRO2 values of 0.67 ± 0.08 µmol/g/min (WM), 3.57 ± 0.67 µmol/g/min (GM), 0.35 ± 0.09 µmol/g/min (CE), and 0.42 ± 0.05 µmol/g/min (PE). In CSF and NE no oxygen uptake (i.e. CMRO2 = 0) was determined from the corrected signals, well in accordance with the underlying physiology in these regions. CONCLUSION: The results show that PVC has a strong effect on the resulting CMRO2 values obtained by (17)O MRI. We found substantial differences-especially in GM tissue-between corrected and non-corrected CMRO2 values. Additionally, we demonstrated the feasibility of CMRO2 assessment in a glioblastoma patient by (17)O MRI.

Cognition and sensation in very high static magnetic fields: a randomized case-crossover study with different field strengths.

PURPOSE: To establish the extent to which representative cognitive functions in subjects undergoing magnetic resonance (MR) imaging are acutely impaired by static magnetic fields of varying field strengths. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed consent was obtained from all subjects. In this single-blind case-crossover study, 41 healthy subjects underwent an extensive neuropsychologic examination while in MR units of differing field strengths (1.5, 3.0, and 7.0 T), including a mock imager with no magnetic field as a control condition. Subjects were blinded to field strength. Tests were performed while subjects were lying still in the MR unit and while the examination table was moved. The tests covered a representative set of cognitive functions, such as memory, eye-hand coordination, attention, reaction time, and visual discrimination. Subjective sensory perceptions were also assessed. Effects were analyzed with a repeated-measures analysis of variance; the within-subject factors were field strength (0, 1.5, 3.0, and 7.0 T) and state (static, dynamic). RESULTS: Static magnetic fields were not found to have a significant effect on cognitive function at any field strength. However, sensory perceptions did vary according to field strength. Dizziness, nystagmus, phosphenes, and head ringing were related to the strength of the static magnetic field. CONCLUSION: Static magnetic fields as high as 7.0 T did not have a significant effect on cognition.

Three-dimensional biexponential weighted (23)Na imaging of the human brain with higher SNR and shorter acquisition time.

A new method is presented for acquiring 3D biexponential weighted sodium images of the in vivo human brain with up to three times higher signal-to-noise ratio compared with conventional six-step phase-cycling triple-quantum-filtered imaging. To excite and detect multiple-quantum coherences, a three-pulse preparation is used. During the pulse train, two images are obtained. The first image is acquired with ultrashort echo time (0.3 ms) during preparation between the first two pulses to yield a spin-density-weighted image. After the last pulse, a single-quantum-filtered image is acquired with an echo time of 11 ms that maximizes the resulting signal. The biexponential weighted image is calculated by subtracting the single-quantum-filtered image from the spin-density-weighted image. The resulting image mainly shows signal from sodium ions with biexponential quadrupolar relaxation behavior. In isotropic environments, the resulting image mainly contains triple-quantum-filtered signal. The four-step phase cycling yields similar signal-to-noise ratio in shorter acquisition time compared with six-step phase-cycling biexponential weighted imaging.

Lung ventilation- and perfusion-weighted Fourier decomposition magnetic resonance imaging: in vivo validation with hyperpolarized 3He and dynamic contrast-enhanced MRI.

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.

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.

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.

Real-time X-ray-based 4D image guidance of minimally invasive interventions.

OBJECTIVE: A new technology is introduced that enables real-time 4D (three spatial dimensions plus time) X-ray guidance for vascular catheter interventions with acceptable levels of ionising radiation. METHODS: The enabling technology is a combination of low-dose tomographic data acquisition with novel compressed sensing reconstruction and use of prior image information. It was implemented in a prototype set-up consisting of a gantry-based flat detector system. In pigs (n = 5) angiographic interventions were simulated. Radiation dosage on a per time base was compared with the "gold standard" of X-ray projection imaging. RESULTS: Contrary to current image guidance methods that lack permanent 4D updates, the spatial position of interventional instruments could be resolved in continuous, spatial 4D guidance; the movement of the guide wire as well as the expansion of stents could be precisely tracked in 3D angiographic road maps. Dose rate was 23.8 µGy/s, similar to biplane standard angiographic fluoroscopy, which has a dose rate of 20.6 µGy/s. CONCLUSION: Real-time 4D X-ray image-guidance with acceptable levels of radiation has great potential to significantly influence the field of minimally invasive medicine by allowing faster and safer interventions and by enabling novel, much more complex procedures for vascular and oncological minimally invasive therapy. KEY POINTS: • Real-time 4D (three spatial dimensions plus time) angiographic intervention guidance is realistic. • Low-dose tomographic data acquisition with special compressed sensing-based algorithms is enabled. • Compared with 4D CT fluoroscopy, this method reduces radiation to acceptable levels. • Once implemented, vascular interventions may become safer and faster. • More complex intervention approaches may be developed.

Spatial localization of genes determined by intranuclear DNA fragmentation with the fusion proteins lamin KRED and histone KRED und visible light.

The highly organized DNA architecture inside of the nuclei of cells is accepted in the scientific world. In the human genome about 3 billion nucleotides are organized as chromatin in the cell nucleus. In general, they are involved in gene regulation and transcription by histone modification. Small chromosomes are localized in a central nuclear position whereas the large chromosomes are peripherally positioned. In our experiments we inserted fusion proteins consisting of a component of the nuclear lamina (lamin B1) and also histone H2A, both combined with the light inducible fluorescence protein KillerRed (KRED). After activation, KRED generates reactive oxygen species (ROS) producing toxic effects and may cause cell death. We analyzed the spatial damage distribution in the chromatin after illumination of the cells with visible light. The extent of DNA damage was strongly dependent on its localization inside of nuclei. The ROS activity allowed to gain information about the location of genes and their functions via sequencing and data base analysis of the double strand breaks of the isolated DNA. A connection between the damaged gene sequences and some diseases was found.

Advanced fit of the diffusion kurtosis tensor by directional weighting and regularization.

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.

Coaxial waveguide MRI.

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.

Synthesis and in vitro evaluation of 68Ga-DOTA-4-FBn-TN14003, a novel tracer for the imaging of CXCR4 expression.

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.

BioShuttle mobility in living cells studied with high-resolution FCS & CLSM methodologies.

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.

Two eyes see more than one: double echo stereoscopic MRA for rapid 3D visualization of vascular structures.

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.

Velocity navigator for motion compensated thermometry.

OBJECT: 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. MATERIALS AND METHODS: A segmented echo planar imaging pulse sequence was modified for velocity-triggered temperature mapping. Trigger events were generated when the estimated velocity value was less than 0.2 cm/s during the slowdown phase in parallel to the velocity-encoding direction. To remove remaining high-frequency spikes from pulsation in real time, a Kalman filter was applied to the velocity navigator data. A phantom experiment with heating and an initial volunteer experiment without heating were performed to show the applicability of this technique. Additionally, a breath-hold experiment was conducted for comparison. RESULTS: A temperature rise of ΔT = +37.3°C was seen in the phantom experiment, and a root mean square error (RMSE) outside the heated region of 2.3°C could be obtained for periodic motion. In the volunteer experiment, a RMSE of 2.7°C/2.9°C (triggered vs. breath hold) was measured. CONCLUSION: A novel velocity navigator with Kalman filter postprocessing in real time significantly improves the temperature accuracy over non-triggered acquisitions and suggests being comparable to a breath-held acquisition. The proposed technique might be clinically applied for monitoring of thermal ablations in abdominal organs.

Cilengitide inhibits progression of experimental breast cancer bone metastases as imaged noninvasively using VCT, MRI and DCE-MRI in a longitudinal in vivo study.

The aim of this study was to investigate the effect of inhibiting αvß(3)/α(v) ß(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 αvß(3) and αvß(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 αvß(3)/αvß(5) inhibition may be a promising therapeutic approach for bone metastases.

Optically detunable, inductively coupled coil for self-gating in small animal magnetic resonance imaging.

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%.