In oncological research, there is a great need for imaging techniques that specifically identify angiogenic blood vessels in tumors on the basis of differences in the expression level of biomolecular markers. In the angiogenic cascade, different cell surface receptors, including the alphavbeta3-integrin, are strongly expressed on activated endothelial cells. In the present study, we aimed to image angiogenesis by detecting the expression of alphavbeta3 in tumor bearing mice with a combination of magnetic resonance imaging (MRI) and fluorescence microscopy. To that end, we prepared MR-detectable and fluorescent liposomes, which carry approximately 700 alphavbeta3-specific RGD peptides per liposome. RGD competition experiments and RAD-conjugated liposomes were used as controls for specificity. In vivo, both RAD liposomes and RGD liposomes gave rise to signal increase on T1-weighted MR images. It was established by the use of ex vivo fluorescence microscopy that RGD liposomes and RAD liposomes accumulated in the tumor by different mechanisms. RGD liposomes were specifically associated with activated tumor endothelium, while RAD liposomes were located in the extravascular compartment. This study demonstrates that MR molecular imaging of angiogenesis is feasible by using a targeted contrast agent specific for the alphavbeta3-integrin, and that the multimodality imaging approach gave insight into the exact mechanism of accumulation in the tumor.

One of the main difficulties in obtaining quantitative perfusion values from dynamic susceptibility contrast-magnetic resonance imaging is a correct arterial input function (AIF) measurement, as partial volume effects can lead to an erroneous shape and amplitude of the AIF. Cerebral blood flow and volume scale linearly with the area under the AIF, but shape changes of the AIF can lead to large, nonlinear errors. Current manual and automated AIF selection procedures do not guarantee the exclusion of partial volume effects from AIF measurements. This study uses a numerical model, validated by phantom experiments, for predicting the optimal location for AIF measurements in the vicinity of the middle cerebral artery (MCA). Three different sequences were investigated and evaluated on a voxel-by-voxel basis by comparison with the ground truth. Subsequently, the predictions were evaluated in an in vivo example. The findings are fourfold: AIF measurements should be performed in voxels completely outside the artery, here a linear relation should be assumed between DR Ã 2 and the concentration contrast agent, the exact optimal location differs per acquisition type, and voxels including a small MCA yield also correct AIF measurements for segmented echo planar imaging when a short echo time was used.

Introduction The increased risk of cerebro- and cardiovascular disease in migraineurs may be the consequence of a systemic condition affecting whole body vasculature. At cerebrovascular level, this may be reflected by interictal global or regional cerebral perfusion abnormalities. Whether focal perfusion changes occur during interictal migraine has not been convincingly demonstrated. Methods We measured brain perfusion with dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in 29 interictal female migraineurs (12 migraine with aura (MA), 17 migraine without aura (MO)) and 16 female controls. Perfusion maps were compared between these groups with a voxelwise (p<0.001, uncorrected, minimum cluster size 20 voxels) and a region-of-interest approach. Results In whole brain voxelwise analyses interictal hyperperfusion was observed in the left medial frontal gyrus in migraineurs and in the inferior and middle temporal gyrus in MO patients, in comparison to controls. Hypoperfusion was seen in the postcentral gyrus and in the inferior temporal gyrus in MA patients and in the inferior frontal gyrus in MO patients. Additional focal sites of hyperperfusion were noted in subgroups based on attack frequency and disease history. Region-of-interest analyses of the pons, hypothalamus, occipital lobe and cerebellum did not show interictal perfusion differences between migraineurs and controls. Conclusion We conclude that interictal migraine is characterized by discrete areas of hyper- and hypoperfusion unspecific for migraine pathophysiology and not explaining the increased vulnerability of particular brain regions for cerebrovascular damage.

Dynamic susceptibility contrast-MRI requires an arterial input function (AIF) to obtain cerebral blood flow, cerebral blood volume, and mean transit time. The current AIF selection criteria discriminate venous, capillary, and arterial profiles based on shape and timing characteristics of the first passage. Unfortunately, partial volume effects can lead to shape errors in the bolus passage, including a narrower and higher peak, which might be selected as a ''correct'' AIF. In this study, a new criterion is proposed that detects shape errors based on tracer kinetic principles for computing cerebral blood volume. This criterion uses the ratio of the steady-state value to the area-under-the-curve of the first passage, which should result in an equal value for tissue and arterial responses. By using a reference value from tissue, partial volume effects-induced shape errors of the AIF measurement can be detected. Different factors affecting the ratio were investigated using simulations. These showed that the new criterion should only be used in studies with T 1 -insensitive acquisition. In vivo data were used to evaluate the proposed approach. The data showed that the new criterion enables detection of shape errors, although false positives do occur, which could be easily avoided when combined with current AIF selection criteria. Magn Reson Med 65:448-456,

In dynamic susceptibility contrast perfusion MRI, arterial input function (AIF) measurements using the phase of the MR signal are traditionally performed inside an artery. However, phasebased AIF selection is also feasible in tissue surrounding an artery such as the middle cerebral artery, which runs approximately perpendicular to B 0 since contrast agents also induce local field changes in tissue surrounding the artery. The aim of this study was to investigate whether phase-based AIF selection is better performed in tissue just outside the middle cerebral artery than inside the artery. Additionally, phasebased AIF selection was compared to magnitude-based AIF selection. Both issues were studied theoretically and using numerical simulations, producing results that were validated using phantom experiments. Finally, an in vivo experiment was performed to illustrate the feasibility of phase-based AIF selection. Three main findings are presented: first, phasebased AIF selections are better made in tissue outside the middle cerebral artery, rather than within the middle cerebral artery, since in the latter approach partial-volume effects affect the shape of the estimated AIF. Second, optimal locations for phase-based AIF selection are similar for different clinical dynamic susceptibility contrast MRI sequences. Third, phase-based AIF selection allows more locations in tissue to be chosen that show the correct AIF than does magnitude-based AIF selection. Magn Reson Med 64:358-368,