The blood oxygen level dependent (BOLD) response, as measured with fMRI, offers good spatial resolution compared to other non-invasive neuroimaging methods. The use of a spin echo technique rather than the conventional gradient echo technique may further improve the resolution by refocusing static dephasing effects around the larger vessels, so sensitizing the signal to the microvasculature. In this work the width of the point spread function (PSF) of the BOLD response at a field strength of 3 Tesla is compared for these two approaches. A double echo EPI pulse sequence with simultaneous collection of gradient echo and spin echo signal allows a direct comparison of the techniques. Rotating multiple-wedge stimuli of different spatial frequencies are used to estimate the width of the BOLD response. Waves of activation are created on the surface of the visual cortex, which begin to overlap as the wedge separation decreases. The modulation of the BOLD response decreases with increasing spatial frequency in a manner dependent on its width. The spin echo response shows a 13% reduction in the width of the PSF, but at a cost of at least 3-fold reduction in contrast to noise ratio. Good spatial resolution is one of the principle advantages of fMRI compared to other neuroimaging methods, such as MEG or EEG. However, compared to most MRI techniques, the typical resolution of the blood oxygenation level dependent (BOLD) response is quite poor. The resolution is limited by physiologic rather than technical considerations, with the vascular response to neural activity extending over several millimeters. The change in deoxyhaemoglobin content in the draining veins and venules leads to inaccurate localization of neural activity (1), and also to poor precision by widening the spatial extent or point spread function (PSF) of the response, resulting in an inability to resolve activity from close sources (2,3). In general, localization and resolution are not related; for example, it is perfectly possible to have very high resolution signal in the wrong location. However, in this case, deoxyhaemoglobin changes in venous vessels distant from the site of neuronal activation will degrade both measures.Recent work suggests that at a field strength of 3T, a spin echo (SE) sequence could improve the spatial resolution of the BOLD response compared to the standard gradient echo (GE) technique (4,5). To understand this we need to consider the relative signal contribution from both the intra-and extravascular spaces. The extravascular signal change is due to the dephasing effect of local field gradients surrounding the blood vessels. Water protons surrounding capillaries will move a considerable distance relative to the capillary diameter during the echo time and, hence, will experience a range of field gradients. This dynamic dephasing is a random process that cannot be refocused by a spin-echo. Water protons surrounding large vessels, however, will tend to remain in the same magnetic field during the echo time, resulting in little dynamic d...

Using a one-step procedure we have prepared magnetic fluids comprising of polyelectrolyte stabilized magnetite nanoparticles. These nanocomposites are comprised of linear, chain-like assemblies of magnetic nanoparticles, which can be aligned in parallel arrays by an external magnetic field. We have shown the potential use of these materials as contrast agents by measuring their MR response in live rats. The new magnetic fluids have demonstrated good biocompatibility and potential for in vivo MRI diagnostics.

Among the changes that typify Alzheimer's disease (AD) are neuroinflammation and microglial activation, amyloid deposition perhaps resulting from compromised microglial function and iron accumulation. Data from Genome Wide Association Studies (GWAS) identified a number of gene variants that endow a significant risk of developing AD and several of these encode proteins expressed in microglia and proteins that are implicated in the immune response. This suggests that neuroinflammation and the accompanying microglial activation are likely to contribute to the pathogenesis of the disease. The trigger(s) leading to these changes remain to be identified. In this study, we set out to examine the link between the inflammatory, metabolic and iron-retentive signature of microglia in vitro and in transgenic mice that overexpress the amyloid precursor protein (APP) and presenilin 1 (PS1; APP/ PS1 mice), a commonly used animal model of AD. Stimulation of cultured microglia with interferon (IFN)γ and amyloid-β (Aβ) induced an inflammatory phenotype and switched the metabolic profile and iron handling of microglia so that the cells became glycolytic and iron retentive, and the phagocytic and chemotactic function of the cells was reduced. Analysis of APP/PS1 mice by magnetic resonance imaging (MRI) revealed genotype-related hypointense areas in the hippocampus consistent with iron deposition, and immunohistochemical analysis indicated that the iron accumulated in microglia, particularly in microglia that decorated Aβ deposits. Isolated microglia prepared from APP/PS1 mice were characterized by a switch to a glycolytic and iron-retentive phenotype and phagocytosis of Aβ was reduced in these cells. This evidence suggests that the switch to glycolysis in microglia may kick-start a cascade of events that ultimately leads to microglial dysfunction and Aβ accumulation.Brain Pathology 29 (2019) 606-621

The effect of thrombolytic therapy was studied in rats submitted to thromboembolic stroke by intracarotid injection of autologous blood clots. Thrombolysis was initiated after 15 minutes with an intracarotid infusion of recombinant tissue-type activator (10 mg/kg body weight). Reperfusion was monitored for 3 hours using serial perfusion- and diffusion magnetic resonance imaging, and the outcome of treatment was quantified by pictorial measurements of ATP, tissue pH, and blood flow. In untreated animals, clot embolism resulted in an immediate decrease in blood flow and a sharp decrease in the apparent diffusion coefficient (ADC) that persisted throughout the observation period. Thrombolysis successfully recanalized the embolized middle cerebral artery origin and led to gradual improvement of blood flow and a slowly progressing reversal of ADC changes in the periphery of the ischemic territory, but only to transient and partial improvement in the center. Three hours after initiation of thrombolysis, the tissue volume with ADC values less than 80% of control was 39 +/- 22% as compared to 61 +/- 20% of ipsilateral hemisphere in untreated animals (means +/- SD, P = .03) and the volume of ATP-depleted brain tissue was 25 +/- 31% as compared to 46 +/- 29% in untreated animals. Recovery of ischemic brain injury after thromboembolism is incomplete even when therapy is started as early as 15 minutes after clot embolism. Possible explanations for our findings include downstream displacement of clot material, microembolism of the vascular periphery, and events associated with reperfusion injury.