Imaging Hyperpolarized Pyruvate and Lactate after Blood-Brain Barrier Disruption with Focused Ultrasound

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Evaluation of tongue squamous cell carcinoma resection margins using ex-vivo MR

Contains fulltext : 174271.pdf (publisher's version ) (Open Access)PURPOSE: Purpose of this feasibility study was (1) to evaluate whether application of ex-vivo 7T MR of the resected tongue specimen containing squamous cell carcinoma may provide information on the resection margin status and (2) to evaluate the research and developmental issues that have to be solved for this technique to have the beneficial impact on clinical outcome that we expect: better oncologic and functional outcomes, better quality of life, and lower costs. METHODS: We performed a non-blinded validation of ex-vivo 7T MR to detect the tongue squamous cell carcinoma and resection margin in 10 fresh tongue specimens using histopathology as gold standard. RESULTS: In six of seven specimens with a histopathologically determined invasion depth of the tumor of [Formula: see text] mm, the tumor could be recognized on MR, with a resection margin within a 2 mm range as compared to histopathology. In three specimens with an invasion depth of [Formula: see text] mm, the tumor was not visible on MR. Technical limitations mainly included scan time, image resolution, and the fact that we used a less available small-bore 7T MR machine. CONCLUSION: Ex-vivo 7T probably will have a low negative predictive value but a high positive predictive value, meaning that in tumors thicker than a few millimeters we expect to be able to predict whether the resection margin is too small. A randomized controlled trial needs to be performed to show our hypothesis: better oncologic and functional outcomes, better quality of life, and lower costs

Structural-functional connectivity deficits of neocortical circuits in the Fmr1 (-/y) mouse model of autism

Contains fulltext : 152752.pdf (publisher's version ) (Open Access)Fragile X syndrome (FXS), the most common inherited form of intellectual disability disorder and a frequent cause of autism spectrum disorder (ASD), is characterized by a high prevalence of sensory symptoms. Perturbations in the anatomical connectivity of neocortical circuits resulting in their functional defects have been hypothesized to contribute to the underlying etiology of these disorders. We tested this idea by probing alterations in the functional and structural connectivity of both local and long-ranging neocortical circuits in the Fmr1 (-/y) mouse model of FXS. To achieve this, we combined in vivo ultrahigh-field diffusion tensor magnetic resonance imaging (MRI), functional MRI, and viral tracing approaches in adult mice. Our results show an anatomical hyperconnectivity phenotype for the primary visual cortex (V1), but a disproportional low connectivity of V1 with other neocortical regions. These structural data are supported by defects in the structural integrity of the subcortical white matter in the anterior and posterior forebrain. These anatomical alterations might contribute to the observed functional decoupling across neocortical regions. We therefore identify FXS as a "connectopathy," providing a translational model for understanding sensory processing defects and functional decoupling of neocortical areas in FXS and ASD

(19)F MRI Imaging Strategies to Reduce Isoflurane Artifacts in In Vivo Images

PURPOSE: Isoflurane (ISO) is the most commonly used preclinical inhalation anesthetic. This is a problem in (19)F MRI of fluorine contrast agents, as ISO signals cause artifacts that interfere with unambiguous image interpretation and quantification; the two most attractive properties of heteronuclear MRI. We aimed to avoid these artifacts using MRI strategies that can be applied by any pre-clinical researcher. PROCEDURES: Three strategies to avoid ISO chemical shift displacement artifacts (CSDA) in (19)F MRI are described and demonstrated with measurements of (19)F-containing agents in phantoms and in vivo (n = 3 for all strategies). The success of these strategies is compared to a standard Rapid Acquisition with Relaxation Enhancement (RARE) sequence, with phantom and in vivo validation. ISO artifacts can successfully be avoided by (1) shifting them outside the region of interest using a narrow signal acquisition bandwidth, (2) suppression of ISO by planning a frequency-selective suppression pulse before signal acquisition or by (3) preventing ISO excitation with a 3D sequence with a narrow excitation bandwidth. RESULTS: All three strategies result in complete ISO signal avoidance (p < 0.0001 for all methods). Using a narrow acquisition bandwidth can result in loss of signal to noise ratio and distortion of the image, and a frequency-selective suppression pulse can be incomplete when B1-inhomogeneities are present. Preventing ISO excitation with a narrow excitation pulse in a 3D sequence yields the most robust results (relative SNR 151 +/- 28% compared to 2D multislice methods, p = 0.006). CONCLUSION: We optimized three easily implementable methods to avoid ISO signal artifacts and validated their performance in phantoms and in vivo. We make recommendation on the parameters that pre-clinical studies should report in their method section to make the used approach insightful

Hypertension, cerebrovascular impairment, and cognitive decline in aged AbetaPP/PS1 mice

Contains fulltext : 174205.pdf (publisher's version ) (Open Access)Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AbetaPPswe/PS1dE9 (AbetaPP/PS1) mouse model for AD. These aging AbetaPP/PS1 mice showed an increased SBP linked to a declined regional CBF. Furthermore, using advanced MRI techniques, decline of functional and structural connectivity was revealed in the AD-like mice coupled to impaired cognition, increased locomotor activity, and anxiety-related behavior. Post mortem analyses demonstrated also increased neuroinflammation, and both decreased synaptogenesis and neurogenesis in the AbetaPP/PS1 mice. Additionally, deviant levels of fatty acids and sterols were present in the brain tissue of the AbetaPP/PS1 mice indicating maladapted brain fatty acid metabolism. Our findings suggest a link between increased SBP, decreased cerebral hemodynamics and connectivity in an AD mouse model during aging, leading to behavioral and cognitive impairments. As these results mirror the complex clinical symptomatology in the prodromal phase of AD, we suggest that this AD-like murine model could be used to investigate prevention and treatment strategies for early AD patients. Moreover, this study helps to develop more efficient therapies and diagnostics for this very early stage of AD

Visualization of calcium phosphate cement in teeth by zero echo time H-1 MRI at high field

Contains fulltext : 184112.pdf (publisher's version ) (Closed access

Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy.

Contains fulltext : 53723.pdf (publisher's version ) (Closed access)Creatine (Cr) levels in skeletal muscle and brain of a mouse model of Cr deficiency caused by guanidinoacetate methyltransferase absence (GAMT-/-) were studied after Cr supplementation with 2 g.kg body wt-1.day-1 Cr for 35 days. Localized 1H magnetic resonance spectroscopy (MRS) was performed in brain (cerebellum and thalamus/hippocampus) and in hind leg muscle of GAMT-/- mice before and after Cr supplementation and in control (Con) mice. As expected, a signal for Cr was hardly detectable in MR spectra of GAMT-/- mice before Cr supplementation. In the thalamus/hippocampus region of these mice, an increase in N-acetylasparate (NAA) was observed. During Cr administration, Cr levels increased faster in skeletal muscle compared with brain, but this occurred only during the first day of supplementation. Thereafter, Cr levels increased by 0.8 mM/day in all studied locations. After 35 days of Cr supplementation, Cr levels in all locations were higher compared with Con mice on a Cr-free diet and NAA levels normalized. Only because of the repeated MRS measurements performed in this longitudinal Cr supplementation study on GAMT-/- mice were we able to discover the initial faster uptake of Cr in skeletal muscle compared with brain, which may represent muscular Cr uptake independent of Cr transporter expression. Our results can provide the basis for additional experiments to optimize Cr supplementation in GAMT deficiency, as increases in brain Cr are slow in patients after Cr supplementation

Cell tracking using (19)F magnetic resonance imaging: Technical aspects and challenges towards clinical applications

Item does not contain fulltext(19)F MRI is emerging as a new imaging technique for cell tracking. It is particularly attractive because of its potential for direct and precise cell quantification. The most important challenge towards in vivo applications is the sensitivity of the technique, i.e. the detection limit in a reasonable imaging time. Optimal sensitivity can be achieved with dedicated (19)F compounds together with specifically adapted hardware and acquisition methods. In this paper we introduce the (19)F MRI technique focusing on these key sensitivity issues and review the state-of-the-art of (19)F MRI and developments towards its clinical use. We calculate (19)F detection limits reported in preclinical cell and clinical (19)F drug studies in terms of tissue concentration in a 1 cm(3) voxel, as an alternate way to compare detection limits. We estimate that a tissue concentration of a few millimoles per litre (mM) of (19)F is required for a human study at a resolution of 1 cm(3). Key Points * Direct and precise cell quantification can be done by (19) F MRI. * (19) F MRI sensitivity is the most important parameter towards clinical application. * A number of (technical) considerations can improve sensitivity significantly. * A few millimoles per litre (mM) of (19) F per voxel is required for adequate detection

Multinutrient diets improve cerebral perfusion and neuroprotection in a murine model of Alzheimer's disease.

Nutritional intervention may retard the development of Alzheimer's disease (AD). In this study we tested the effects of 2 multi-nutrient diets in an AD mouse model (APPswe/PS1dE9). One diet contained membrane precursors such as omega-3 fatty acids and uridine monophosphate (DEU), whereas another diet contained cofactors for membrane synthesis as well (Fortasyn); the diets were developed to enhance synaptic membranes synthesis, and contain components that may improve vascular health. We measured cerebral blood flow (CBF) and water diffusivity with ultra-high-field magnetic resonance imaging, as alterations in these parameters correlate with clinical symptoms of the disease. APPswe/PS1dE9 mice on control diet showed decreased CBF and changes in brain water diffusion, in accordance with findings of hypoperfusion, axonal disconnection and neuronal loss in patients with AD. Both multinutrient diets were able to increase cortical CBF in APPswe/PS1dE9 mice and Fortasyn reduced water diffusivity, particularly in the dentate gyrus and in cortical regions. We suggest that a specific diet intervention has the potential to slow AD progression, by simultaneously improving cerebrovascular health and enhancing neuroprotective mechanisms

Nuclear magnetic resonance in laboratory animals.

Contains fulltext : 58824.pdf (publisher's version ) (Closed access