Diffusion-weighted imaging and dynamic contrast-enhanced MRI of experimental breast cancer bone metastases--a correlation study with histology.

PURPOSE: To validate imaging parameters from diffusion-weighted imaging and dynamic contrast-enhanced MRI with immunohistology and to non-invasively assess microstructure of experimental breast cancer bone metastases. MATERIALS AND METHODS: Animals bearing breast cancer bone metastases were imaged in a clinical 1.5 T MRI scanner. HASTE sequences were performed to calculate apparent diffusion coefficients. Saturation recovery turbo FLASH sequences were conducted while infusing 0.1 mmol/l Gd-DTPA for dynamic contrast-enhanced MRI to quantify parameters amplitude A and exchange rate constant kep. After imaging, bone metastases were analyzed immunohistologically. RESULTS: We found correlations of the apparent diffusion coefficients from diffusion-weighted imaging with tumor cellularity as assessed with cell nuclei staining. Histological vessel maturity was correlated negatively with parameters A and kep from dynamic contrast-enhanced MRI. Tumor size correlated inversely with cell density and vessel permeability as well as positively with mean vessel calibers. Parameters from the rim of bone metastases differed significantly from values of the center. CONCLUSION: In vivo diffusion-weighted imaging and dynamic contrast-enhanced MRI in experimental bone metastases provide information about tumor cellularity and vascularity and correlate well with immunohistology.

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.

Women are more strongly affected by dizziness in static magnetic fields of magnetic resonance imaging scanners.

Increasing field strengths in MRI necessitate the examination of potential side effects. Previously reported results have been contradictory, possibly caused by imbalanced samples. We aimed to examine whether special groups of people are more prone to develop side effects that might have led to contradictory results in previous studies. We examined the occurrence of sensory side effects in static magnetic fields of MRI scanners of 1.5, 3, and 7 T and a mock scanner in 41 healthy participants. The contribution of field strength, sex, age, and attention to bodily processes, and stress hormone levels to the sensation of dizziness was examined in separate univariate analyses and in a joint analysis that included all variables. Field strength and sex were significant factors in the joint analysis (P=0.001), with women being more strongly affected than men by dizziness in higher static magnetic fields. This effect was not mediated by the other variables such as attention to bodily symptoms or stress hormones. Further research needs to elucidate the underlying factors of increased dizziness in women in static magnetic fields in MRI. We hypothesize that imbalanced samples of earlier studies might be one reason for previous contradictory results on the side effects of static magnetic fields.

Assessing treatment response of osteolytic lesions by manual volumetry, automatic segmentation, and RECIST in experimental bone metastases.

RATIONALE AND OBJECTIVES: Aim of the study was to compare between volumetric and unidimensional approaches for treatment response monitoring in a nude rat model of experimental bone metastases. For the volumetric approach, an automated segmentation algorithm of osteolytic lesions was introduced and compared to manual volumetry. MATERIAL AND METHODS: Nude rats bearing osteolytic metastases were treated with zoledronate and sunitinib and compared to controls. Treatment response was assessed longitudinally in vivo using flat-panel volumetric computed tomography at days 30, 35, 45, and 55 after tumor cell inoculation. The mean sizes and volumes of osteolytic lesions were determined according to response evaluation criteria in solid tumors (RECIST) and by automated and manual volumetry (software: MITK [The Medical Imaging Interaction Toolkit, Heidelberg, Germany] and VIRTUOS, Heidelberg, Germany). RESULTS: In contrary to RECIST, the manual volumetric approach indicated a significant decrease in osteolytic lesion volume in response to treatment. The presented automatic segmentation algorithm for treatment monitoring identified bone metastases adequately and assessed changes in the osteolytic lesion volume over time according to manual volumetry. CONCLUSIONS: In an animal model, volumetric treatment response assessment of osteolytic bone metastases is superior to unidimensional measurements, and automated volumetric segmentation may be a valuable alternative to manual volume determination.

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.

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.

Multicenter study of subjective acceptance during magnetic resonance imaging at 7 and 9.4 T.

OBJECTIVES: The aims of this study were to investigate the subjective discomfort and sensory side effects during ultrahigh field (UHF) magnetic resonance imaging (MRI) examinations in a large-scale study and to evaluate differences between magnetic resonance (MR) sites. MATERIALS AND METHODS: Four MR sites with a 7-T MR system and 2 MR sites with a 9.4-T MR system participated in this multicenter study with a total number of 3457 completed questionnaires on causes of discomfort and sensations during the examination. For a pooled retrospective analysis of the results from the partially different questionnaires, all data were adapted to an answer option with a 4-point scale (0 = no discomfort/side effect, 3 = very unpleasant/very strong sensation). To differentiate effects evoked by the low-frequency time-varying magnetic fields due to movement through the static magnetic field, most questionnaires separated the manifestation of sensory side effects during movement on the patient table from manifestation while lying still in the isocenter. RESULTS: In general, a high acceptance of UHF examinations was found, where in 82% of the completed questionnaires, the subjects stated the examination to be at least tolerable. Although in 7.6% of the questionnaires, subjects felt discomfort during the examination, only 0.9% of the image acquisitions had to be terminated prematurely. No adverse events occurred in any of the examinations. Only 1% of the subjects were unwilling to undergo further UHF MRI examinations. Examination duration was the most complained cause of discomfort, followed by acoustic noise and lying still. All magnetic-field-related sensations were more pronounced when moving the patient table versus the isocenter position (19%/2% of the subjects felt unpleasant vertigo during the moving/stationary state). In general, vertigo was the most often stated sensory side effect and was more pronounced at 9.4 T compared with 7 T. However, the results varied substantially among the different sites. CONCLUSIONS: The high levels of subjective acceptance found in this study lead to the conclusion that UHF MRI would be tolerated as a diagnostic tool in clinical practice. For more consistent data ascertainment, we propose a standardized questionnaire for subjective perception monitoring.

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.

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.

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.

Tracking of an interventional catheter with a ferromagnetic tip using dual-echo projections.

Interventional devices with ferromagnetic components can be manipulated remotely using forces induced by the MRI gradients. To deflect the tip of an endovascular catheter, large ferromagnetic spheres of 2 mm diameter are required to exert sufficiently high magnetic forces; however, tracking of these devices is difficult due to the large image artifacts. In this study, a new dual-echo technique is proposed to improve the stability of localizing and tracking medical devices with ferromagnetic components. MR tracking methods with selective off-resonant excitation and phase compensation with a rephasing gradient can detect ferromagnetic spheres up to a diameter of 1 mm only. In this work, a dual-echo technique is used with two rephasing gradients to stabilize the off-set localization. With rephasing being applied in orthogonal directions, an SNR of 5 was achieved in the signal projections. Compared to a single-echo acquisition the dual-echo method reduces the position error in a phantom from 8 mm to 1.6 mm. In an in vivo study a tracking precision of 4 mm was measured without steering gradients at an image update rate of 2 images per second. Steering experiments were successfully performed with a prototype catheter with ferromagnetic sphere in an aorta phantom and in the vena cava of a pig.

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.

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.

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.

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.

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.

Calibration of cone beam CT using relative attenuation ratio for quantitative assessment of bone density: a small animal study.

PURPOSE: Cone beam computed tomography (CBCT) has the disadvantage of providing non-quantitative results for bone density determination. The aim of this study is to calibrate CBCT results by using an internal reference (such as muscle) for quantitatively assessing bone density. METHODS: We developed a new method using the relative attenuation ratio between two nearby materials (such as bone and muscle) for systemic error correction in CBCT that depends on the relative object position in the image volume. Phantom calibration was performed to calculate the acquired attenuation ratio in Hounsfield units (HU), comparable to the results from clinical multislice spiral computed tomography (MSCT). In addition, a small animal study with an osteoporotic rat model was evaluated to show the feasibility of this presented method to quantitatively assess bone density using a CBCT system. RESULTS: The phantom study results showed that the calibration process successfully corrected the systemic inaccuracy from CBCT, and the calibrated HU values agreed with the values measured from MSCT. In the small animal study, the quantitative bone densities assessed from the calibrated CBCT results were consistent with the results from MSCT data. CONCLUSION: A practical method to quantitatively estimate attenuation (HU) values for bone tissues from CBCT scans that are comparable to MSCT scans is proposed. The method may improve the quantification ability of CBCT scanning without any additional hardware requirements.

Cilengitide affects tumor compartment, vascularization and microenvironment in experimental bone metastases as shown by longitudinal ¹8F-FDG PET and gene expression analysis.

PURPOSE: Aim of this study was to investigate the specific treatment effects of inhibiting αvß3/αvß5 integrins by cilengitide in an animal model of breast cancer bone metastases using dynamic (18)F-FDG PET and gene expression analysis. METHODS: For this purpose, nude rats bearing bone metastases were treated with cilengitide, a small molecule inhibitor of αvß3 and αvß5 integrins, from day 30 to 55 after tumor cell inoculation of MDA-MB-231 breast cancer cells (25 mg/kg, 5 days per week; n = 8 rats) and compared to control rats (n = 8). Dynamic (18)F-FDG PET data were assessed at days 30, 35 and 55 after tumor cell inoculation determining the vascular fraction VB and the metabolic variables k1-k4. At day 55, genome-wide mRNA expression analysis was performed to assess the treatment-specific expression changes from cilengitide-treated and control rats. RESULTS: In a longitudinal (18)F-FDG PET study, the vascular fraction VB was significantly decreased in bone metastases between days 30/35, 30/55 and 35/55, whereas the kinetic parameters k1 and k4 were significantly decreased between days 30/55 in skeletal lesions of treated animals. Gene expression analysis from bone metastases at day 55 revealed that tumor-produced integrins (αvß5) as well as factors relevant for angiogenesis (αvß3, VEGF, PDGF), bone resorption (PTHrP and RANKL), extracellular matrix remodeling (collagen, CD44) and bone marrow microenvironment (CXCR4) were significantly reduced upon therapy with cilengitide. CONCLUSIONS: Here, we provide evidence that cilengitide inhibits pivotal factors of all compartments of bone metastases including tumor cells, vasculature and bone microenvironment in vivo and by whole-genome transcriptome analysis.

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.

NMR-based diffusion pore imaging.

Nuclear magnetic resonance (NMR) diffusion experiments offer a unique opportunity to study boundaries restricting the diffusion process. In a recent Letter [Phys. Rev. Lett. 107, 048102 (2011)], we introduced the idea and concept that such diffusion experiments can be interpreted as NMR imaging experiments. Consequently, images of closed pores, in which the spins diffuse, can be acquired. In the work presented here, an in-depth description of the diffusion pore imaging technique is provided. Image artifacts due to gradient profiles of finite duration, field inhomogeneities, and surface relaxation are considered. Gradients of finite duration lead to image blurring and edge enhancement artifacts. Field inhomogeneities have benign effects on diffusion pore images, and surface relaxation can lead to a shrinkage and shift of the pore image. The relation between boundary structure and the imaginary part of the diffusion weighted signal is analyzed, and it is shown that information on pore coherence can be obtained without the need to measure the phase of the diffusion weighted signal. Moreover, it is shown that quite arbitrary gradient profiles can be used for diffusion pore imaging. The matrices required for numerical calculations are stated and provided as supplemental material.