Aerobic interval training reduces inducible ventricular arrhythmias in diabetic mice after myocardial infarction.

Diabetes mellitus (DM) increases the risk of heart failure after myocardial infarction (MI), and aggravates ventricular arrhythmias in heart failure patients. Although exercise training improves cardiac function in heart failure, it is still unclear how it benefits the diabetic heart after MI. To study the effects of aerobic interval training on cardiac function, susceptibility to inducible ventricular arrhythmias and cardiomyocyte calcium handling in DM mice after MI (DM-MI). Male type 2 DM mice (C57BLKS/J Lepr (db) /Lepr (db) ) underwent MI or sham surgery. One group of DM-MI mice was submitted to aerobic interval training running sessions during 6 weeks. Cardiac function and structure were assessed by echocardiography and magnetic resonance imaging, respectively. Ventricular arrhythmias were induced by high-frequency cardiac pacing in vivo. Protein expression was measured by Western blot. DM-MI mice displayed increased susceptibility for inducible ventricular arrhythmias and impaired diastolic function when compared to wild type-MI, which was associated with disruption of cardiomyocyte calcium handling and increased calcium leak from the sarcoplasmic reticulum. High-intensity exercise recovered cardiomyocyte function in vitro, reduced sarcoplasmic reticulum diastolic calcium leak and significantly reduced the incidence of inducible ventricular arrhythmias in vivo in DM-MI mice. Exercise training also normalized the expression profile of key proteins involved in cardiomyocyte calcium handling, suggesting a potential molecular mechanism for the benefits of exercise in DM-MI mice. High-intensity aerobic exercise training recovers cardiomyocyte function and reduces inducible ventricular arrhythmias in infarcted diabetic mice.

Transverse relaxivity of iron oxide nanocrystals clustered in nanoemulsions: Experiment and theory.

PURPOSE: To compare experimental transverse relaxivities of iron oxide nanocrystals (IONC) as a function of clustering and magnetic field strength with different theoretical model predictions. THEORY AND METHODS: Well-defined IONC clusters in nanoemulsions (NEs) of which both size and IONC loading could be judiciously tuned were developed. Transverse relaxivities were measured as a function of NE size and IONC loading at 20 and 300 MHz and compared with four theoretical model predictions. Polydispersity of the NEs was measured and taken into account in the theoretical calculations. RESULTS: Experimentally observed relaxivities were in between theoretical predictions from the fast diffusion regime and the static dephasing regimen. NE polydispersity significantly affected the theoretical T2 relaxivity. The effect of both the number of IONCs inside each droplet as well as the radius of the droplet itself was correctly described by a fast diffusion loose aggregate model, while the effect of increased magnetic field was in agreement with a static dephasing model. CONCLUSION: The results suggest that both fast diffusion, originating from bulk water, and static dephasing phenomena, perhaps originating from water associated with the NE, play a role in transverse relaxivities of IONC aggregates. The developed aggregate system represents a powerful tool to further study these phenomena.

Dynamic contrast enhanced MRI detects early response to adoptive NK cellular immunotherapy targeting the NG2 proteoglycan in a rat model of glioblastoma.

There are currently no established radiological parameters that predict response to immunotherapy. We hypothesised that multiparametric, longitudinal magnetic resonance imaging (MRI) of physiological parameters and pharmacokinetic models might detect early biological responses to immunotherapy for glioblastoma targeting NG2/CSPG4 with mAb9.2.27 combined with natural killer (NK) cells. Contrast enhanced conventional T1-weighted MRI at 7±1 and 17±2 days post-treatment failed to detect differences in tumour size between the treatment groups, whereas, follow-up scans at 3 months demonstrated diminished signal intensity and tumour volume in the surviving NK+mAb9.2.27 treated animals. Notably, interstitial volume fraction (ve), was significantly increased in the NK+mAb9.2.27 combination therapy group compared mAb9.2.27 and NK cell monotherapy groups (p = 0.002 and p = 0.017 respectively) in cohort 1 animals treated with 1 million NK cells. ve was reproducibly increased in the combination NK+mAb9.2.27 compared to NK cell monotherapy in cohort 2 treated with increased dose of 2 million NK cells (p<0.0001), indicating greater cell death induced by NK+mAb9.2.27 treatment. The interstitial volume fraction in the NK monotherapy group was significantly reduced compared to mAb9.2.27 monotherapy (p<0.0001) and untreated controls (p = 0.014) in the cohort 2 animals. NK cells in monotherapy were unable to kill the U87MG cells that highly expressed class I human leucocyte antigens, and diminished stress ligands for activating receptors. A significant association between apparent diffusion coefficient (ADC) of water and ve in combination NK+mAb9.2.27 and NK monotherapy treated tumours was evident, where increased ADC corresponded to reduced ve in both cases. Collectively, these data support histological measures at end-stage demonstrating diminished tumour cell proliferation and pronounced apoptosis in the NK+mAb9.2.27 treated tumours compared to the other groups. In conclusion, ve was the most reliable radiological parameter for detecting response to intralesional NK cellular therapy.

Periodicity in tumor vasculature targeting kinetics of ligand-functionalized nanoparticles studied by dynamic contrast enhanced magnetic resonance imaging and intravital microscopy.

In the past two decades advances in the development of targeted nanoparticles have facilitated their application as molecular imaging agents and targeted drug delivery vehicles. Nanoparticle-enhanced molecular imaging of the angiogenic tumor vasculature has been of particular interest. Not only because angiogenesis plays an important role in various pathologies, but also since endothelial cell surface receptors are directly accessible for relatively large circulating nanoparticles. Typically, nanoparticle targeting towards these receptors is studied by analyzing the contrast distribution on tumor images acquired before and at set time points after administration. Although several exciting proof-of-concept studies demonstrated qualitative assessment of relative target concentration and distribution, these studies did not provide quantitative information on the nanoparticle targeting kinetics. These kinetics will not only depend on nanoparticle characteristics, but also on receptor binding and recycling. In this study, we monitored the in vivo targeting kinetics of αvß3-integrin specific nanoparticles with intravital microscopy and dynamic contrast enhanced magnetic resonance imaging, and using compartment modeling we were able to quantify nanoparticle targeting rates. As such, this approach can facilitate optimization of targeted nanoparticle design and it holds promise for providing more quantitative information on in vivo receptor levels. Interestingly, we also observed a periodicity in the accumulation kinetics of αvß3-integrin targeted nanoparticles and hypothesize that this periodicity is caused by receptor binding, internalization and recycling dynamics. Taken together, this demonstrates that our experimental approach provides new insights in in vivo nanoparticle targeting, which may proof useful for vascular targeting in general.

Late gadolinium enhancement in the assessment of the infarcted mouse heart: a longitudinal comparison with manganese-enhanced MRI.

PURPOSE: To evaluate late gadolinium-enhanced (LGE) assessment of infarct size, a comparison with manganese-enhanced magnetic resonance imaging (MEMRI), and histology was performed in a permanent infarction model in the mouse at the acute and chronic stage. MATERIALS AND METHODS: In a paired fashion at the acute and chronic stage after infarction (3-4 days and 21 days, respectively), LGE and MEMRI was performed using a self-gated fast low flip angle shot (FLASH). Infarct size was evaluated as the enhanced area relative to the complete myocardial wall area in a mid-ventricular slice. Paired comparisons were made between contrast agents and between timepoints, as well as to histology. RESULTS: At the acute stage, LGE delineated a larger infarct size as compared to both MEMRI and histology. Infarct size from LGE decreased from the acute to chronic stage, a temporal development not seen with MEMRI. At the chronic stage, no significant differences in infarct size were found between the methods. CONCLUSION: This study indicates an overenhancement of infarct size when using LGE, supported by an initial overestimation at the acute stage and a temporal decrease in infarct size from the acute to chronic stage, as compared to infarct size from MEMRI.

The effect of nanoparticle polyethylene glycol surface density on ligand-directed tumor targeting studied in vivo by dual modality imaging.

The development and application of nanoparticles as in vivo delivery vehicles for therapeutic and/or diagnostic agents has seen a drastic growth over the last decades. Novel imaging techniques allow real-time in vivo study of nanoparticle accumulation kinetics at the level of the cell and targeted tissue. Successful intravenous application of such nanocarriers requires a hydrophilic particle surface coating, of which polyethylene glycol (PEG) has become the most widely studied and applied. In the current study, the effect of nanoparticle PEG surface density on the targeting efficiency of ligand-functionalized nanoemulsions was investigated. We synthesized 100 nm nanoemulsions with a PEG surface density varying from 5 to 50 mol %. Fluorescent and paramagnetic lipids were included to allow their multimodal detection, while RGD peptides were conjugated to the PEG coating to obtain specificity for the α(v)ß(3)-integrin. The development of a unique experimental imaging setup allowed us to study, in real time, nanoparticle accumulation kinetics at (sub)-cellular resolution in tumors that were grown in a window chamber model with confocal microscopy imaging, and at the macroscopic tumor level in subcutaneously grown xenografts with magnetic resonance imaging. Accumulation in the tumor occurred more rapidly for the targeted nanoemulsions than for the nontargeted versions, and the PEG surface density had a strong effect on nanoparticle targeting efficiency. Counterintuitively, yet consistent with the PEG density conformation models, the highest specificity and targeting efficiency was observed at a low PEG surface density.

Labelling of olfactory ensheathing cells with micron-sized particles of iron oxide and detection by MRI.

A crucial issue in transplant-mediated repair of the damaged central nervous system (CNS) is serial non-invasive imaging of the transplanted cells, which has led to interest in the application of magnetic resonance imaging (MRI) combined with designated intracellular magnetic labels for cell tracking. Micron-sized particles of iron oxide (MPIO) have been successfully used to track cells by MRI, yet there is relatively little known about either their suitability for efficient labelling of specific cell types, or their effects on cell viability. The purpose of this study was to develop a suitable MPIO labelling protocol for olfactory ensheathing cells (OECs), a type of glia used to promote the regeneration of CNS axons after transplantation into the injured CNS. Here, we demonstrate an OEC labelling efficiency of >90% with an MPIO incubation time as short as 6 h, enabling intracellular particle uptake for single-cell detection by MRI without affecting cell proliferation, migration and viability. Moreover, MPIO are resolvable in OECs transplanted into the vitreous body of adult rat eyes, providing the first detailed protocol for efficient and safe MPIO labelling of OECs for non-invasive MRI tracking of transplanted OECs in real time for use in studies of CNS repair and axon regeneration.

Evaluation of intracellular labeling with micron-sized particles of iron oxide (MPIOs) as a general tool for in vitro and in vivo tracking of human stem and progenitor cells.

Magnetic resonance imaging (MRI)-based tracking is increasingly attracting attention as a means of better understanding stem cell dynamics in vivo. Intracellular labeling with micrometer-sized particles of iron oxide (MPIOs) provides a practical MRI-based approach due to superior detectability relative to smaller iron oxide particles. However, insufficient information is available about the general utility across cell types and the effects on cell vitality of MPIO labeling of human stem cells. We labeled six human cell types from different sources: mesenchymal stem cells derived from bone marrow (MSCs), mesenchymal stem cells derived from adipose tissue (ASCs), presumptive adult neural stem cells (ad-NSCs), fetal neural progenitor cells (f-NPCs), a glioma cell line (U87), and glioblastoma tumor stem cells (GSCs), with two different sizes of MPIOs (0.9 and 2.84 µm). Labeling and uptake efficiencies were highly variable among cell types. Several parameters of general cell function were tested in vitro. Only minor differences were found between labeled and unlabeled cells with respect to proliferation rate, mitotic duration, random motility, and capacity for differentiation to specific phenotypes. In vivo behavior was tested in chicken embryos and severe combined immunodeficient (SCID) mice. Postmortem histology showed that labeled cells survived and could integrate into various tissues. MRI-based tracking over several weeks in the SCID mice showed that labeled GSCs and f-NPCs injected into the brain exhibited translocations similar to those seen for unlabeled cells and as expected from migratory behavior described in previous studies. The results support MPIO-based cell tracking as a generally useful tool for studies of human stem cell dynamics in vivo.

In vivo MRI of olfactory ensheathing cell grafts and regenerating axons in transplant mediated repair of the adult rat optic nerve.

The purpose of the present study was to use magnetic resonance imaging (MRI) as a tool for monitoring transplant-mediated repair of the adult rat visual pathway. We labelled rat olfactory ensheathing cells (OECs) using micron-sized particles of iron oxide (MPIO) and transplanted them by: i) intravitreal injection (ivit) and ii) intra-optic nerve (ON) injection (iON) in adult rats with ON crush (ONC) injury. We applied T(2)-weighted MRI and manganese-enhanced MRI (MEMRI) to visualise transplanted cells and ON axons at specific times after injury and cell engraftment. Our findings demonstrate that ivit MPIO-labelled OECs are unequivocally detected by T(2)-weighted MRI in vivo and that the T(1)-weighted 3D FLASH sequence applied for MEMRI facilitates simultaneous visualisation of Mn(2+-) enhanced regenerating retinal ganglion cell (RGC) axons and MPIO-labelled OEC grafts. Furthermore, analysis of MRI data and ultrastructural findings supports the hypothesis that iON OEC transplants mediate regeneration and remyelination of RGC axons post injury.

Mn-alginate gels as a novel system for controlled release of Mn2+ in manganese-enhanced MRI.

The aim of the present study was to test alginate gels of different compositions as a system for controlled release of manganese ions (Mn(2+)) for application in manganese-enhanced MRI (MEMRI), in order to circumvent the challenge of achieving optimal MRI resolution without resorting to high, potentially cytotoxic doses of Mn(2+). Elemental analysis and stability studies of Mn-alginate revealed marked differences in ion binding capacity, rendering Mn/Ba-alginate gels with high guluronic acid content most stable. The findings were corroborated by corresponding differences in the release rate of Mn(2+) from alginate beads in vitro using T(1)-weighted MRI. Furthermore, intravitreal (ivit) injection of Mn-alginate beads yielded significant enhancement of the rat retina and retinal ganglion cell (RGC) axons 24 h post-injection. Subsequent compartmental modelling and simulation of ivit Mn(2+) transport and concentration revealed that application of slow release contrast agents can achieve a significant reduction of ivit Mn(2+) concentration compared with bolus injection. This is followed by a concomitant increase in the availability of ivit Mn(2+) for uptake by RGC, corresponding to significantly increased time constants. Our results provide proof-of-concept for the applicability of Mn-alginate gels as a system for controlled release of Mn(2+) for optimized MEMRI application.

Assessment of left ventricular function by GPs using pocket-sized ultrasound.

BACKGROUND: Assessment of left ventricular (LV) function with echocardiography is mandatory in patients with suspected heart failure (HF). OBJECTIVES: To investigate if GPs were able to evaluate the LV function in patients at risk of developing or with established HF by using pocket-sized ultrasound (pUS). METHODS: Feasibility study in general practice, seven GPs in three different Norwegian primary care centres participated. Ninety-two patients with reduced or at risk of developing reduced LV function were examined by their own GP using pUS. The scan (<5 minute) was done as part of a routine appointment. A cardiologist examined the patients <30 minutes afterwards with both a laptop scanner and pUS. Measurements of the septal mitral annular excursion (sMAE) were compared. RESULTS: In 87% of the patients, the GPs were able to obtain a standard view and measure the sMAE. There was a non-significant mean difference in sMAE between GP pUS and cardiologist laptop scanner of -0.15 mm 95% confidence interval (-0.60 to 0.30) mm. A comparison of the pUS recordings and measurements of sMAE made by GP versus cardiologist revealed a non-significant mean difference with acceptable 95% limits of agreement (-0.26 ± 3.02 mm). CONCLUSIONS: With tailored training, GPs were able to assess LV function with sMAE and pUS. pUS, as a supplement to the physical examination, may become an important tool in general practice.

Entorhinal cortical thinning affects perceptual and cognitive functions in adolescents born preterm with very low birth weight (VLBW).

BACKGROUND: The entorhinal cortex serves as an important gateway between the cerebral cortex and the hippocampus by receiving afferent information from limbic, modality sensory-specific, and multimodal association fibers from all the brain lobes. AIM: To investigate whether thinning of entorhinal cortex is associated with reduced perceptual, cognitive and executive skills in very low birth weight (VLBW) adolescents. STUDY DESIGN: Prospective, geographically based follow-up study of three year cohorts of preterm born VLBW children. SUBJECTS: Forty-nine VLBW (birth weight ≤ 1500 g) and 58 term-born control adolescents were examined at the age of 14-15 years. OUTCOME MEASURES: Perceptual and cognitive functions were assessed with Visual motor integration test, Grooved Pegboard test, Wechsler Intelligence Scale for Children-III and different executive function tests (Wisconsin card sorting test, Trail Making test, Knox cube test). An automated MRI technique at 1.5 T for morphometric analyses of cortical thickness was performed. Areas with cortical thinning in left and right entorhinal cortex in the VLBW group were chosen as regions of interest to look for associations between cortical thickness and clinical findings. RESULTS: Thinning of the entorhinal cortex was correlated with low performance on perceptual and cognitive scores in the VLBW adolescents, but not in controls. In addition, thinning of the entorhinal cortices correlated with reduced performance on several executive tests, including perceptual speed and aspects of working memory. CONCLUSIONS: Entorhinal cortical thinning is related with low IQ and reduced perceptual and executive functions in VLBW adolescents.

Visual function and white matter microstructure in very-low-birth-weight (VLBW) adolescents--a DTI study.

Premature birth is associated with visual impairments, due to both cerebral and ocular pathology. This study examined the relationship between cerebral white matter microstructure, evaluated by diffusion tensor imaging (DTI), and visual function, in 30 preterm born adolescents with very low birth weight (VLBW=birth weight⩽1500g) and an age-matched group of 45 term born controls. Visual acuity correlated positively with fractional anisotropy (FA) in corpus callosum and in frontal white matter areas in the VLBW participants, but not in the control participants. Callosal visual connections may play a more important role in the development of good visual acuity than previously acknowledged in preterm born children.

Manganese transport in the rat optic nerve evaluated with spatial- and time-resolved magnetic resonance imaging.

PURPOSE: 1) To evaluate a novel theoretical model for in vivo axonal Mn(2+) transport with MRI data from the rat optic nerve (ON); and 2) to compare predictions from the new model with previously reported experimental data. MATERIALS AND METHODS: Time-resolved in vivo T(1)-weighted magnetic resonance imaging (MRI) of adult female Sprague-Dawley rat (n = 9) ON was obtained at different timepoints after intravitreal MnCl(2) injection. A concentration-dependent and a rate-dependent function for the Mn(2+) retinal ganglion cell (RGC) axon entrance was convolved with three different transport functions and each model system was optimized to fit the ON data. RESULTS: The rate-limited input function gave a better fit to the data than the concentration-limited input. Simulations showed that the rate-limited input leads to a semilogarithmic relationship between injected dose and Mn(2+) concentration in the ON, which is in agreement with previously reported in vivo experiments. A random walk transport model and an anterograde predominant slow model gave a similar fit to the data, both better than an anterograde predominant fast model. CONCLUSION: The results indicate that Mn(2+) input into RGC axons is limited by a maximum entrance rate into the axons. Also, a wide range of apparent Mn(2+) transport rates seems to be involved, different from synaptic vesicle transport rates, meaning that manganese does not depict synaptic vesicle transport rates directly.

Intravital microscopy in window chambers: a unique tool to study tumor angiogenesis and delivery of nanoparticles.

Solid tumor growth is heavily dependant on angiogenesis. Tumor angiogenesis is the result of a complex interplay between tumor cells, endothelial cells, and other stromal cells. It has been found to be under strict control of a plethora of molecular factors that function as angiogenic up- and down-regulators; nevertheless, the identification of molecular and cellular players and their roles in angiogenesis is still ongoing. The microvasculature resulting from tumor angiogenesis lacks hierarchy and has a high permeability for macromolecules and nanoparticles, which offers significant potential for nanoparticulate tumor imaging and drug delivery platforms. However, improvements in the delivery to poorly vascularized regions and the distribution throughout the tumor interstitium are critical for nanoparticles to become more effective in the battle against cancer. A tool that has proven extremely valuable in both unraveling angiogenic pathways and characterizing in vivo nanoparticle behavior in solid tumors is intravital microscopy of tumors grown in window chamber preparations. In this review this technique is explained, several exciting examples illustrating its value in elucidating tumor angiogenesis are presented and the study of nanoparticle behavior in solid tumors using this approach is described. We conclude with a discussion of the potential value of intravital microscopy in window chambers in multimodality studies of tumor pathophysiology and nanoparticle dynamics.

Segmental brain volumes and cognitive and perceptual correlates in 15-year-old adolescents with low birth weight.

OBJECTIVE: To determine whether preterm very low birth weight (VLBW) or term born small for gestational age (SGA) adolescents have reduced regional brain volumes. We also asked which perinatal factors are related to reduced brain volume in VLBW adolescents, which regional brain volumes are associated with cognitive and perceptual functioning, and if these differ between the groups. STUDY DESIGN: Fifty adolescent preterm VLBW (< or =1500 g) births and 49 term SGA births (birth weight <10th percentile) were compared with 57 normal-weight term births. An automated MRI segmentation technique was used. Cognitive and perceptual functions were evaluated by WISC-III and Visual Motor Integration (VMI) tests. RESULTS: The VLBW group had reduced volumes for thalamus and cerebellar white matter (P < .002). The SGA group had smaller total brains, and proportionally smaller regional brain volumes. Cerebellar white matter in the VLBW, hippocampus in the SGA, and cerebral cortical in the control group were volumes that significantly predicted cognitive and perceptual functions. CONCLUSIONS: We speculate that white matter injury may explain the impaired cognitive and perceptual functioning in the prematurely born, whereas hippocampal injury may be related to cognitive dysfunction in term SGA adolescents.

White matter abnormalities and executive function in children with very low birth weight.

The aim of this study was to investigate any structural-functional relationship between changes in white matter microstructure seen on diffusion tensor imaging and results of an executive function test in adolescents with very low birth weight (VLBW). Thirty-four VLBW adolescents were examined at 15 years of age. Executive function was assessed by the Wisconsin Card Sorting Test. Diffusion tensor imaging scans were performed at 1.5 T for calculation of individual fractional anisotropy maps. Through a voxel-wise regression analysis, correlations were found between the results on Wisconsin Card Sorting Test and fractional anisotropy values in the left cingulum and both inferior fronto-occipital fascicles. We speculate that impairments in executive function in VLBW children may be influenced by disturbed connectivity between posterior brain regions and the prefrontal cortex.

Combination of Mn(2+)-enhanced and diffusion tensor MR imaging gives complementary information about injury and regeneration in the adult rat optic nerve.

PURPOSE: To evaluate manganese (Mn(2+))-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) as tools for detection of axonal injury and regeneration after intravitreal peripheral nerve graft (PNG) implantation in the rat optic nerve (ON). MATERIALS AND METHODS: In adult Fischer rats, retinal ganglion cell (RGC) survival was evaluated in Flurogold (FG) back-filled retinal whole mounts after ON crush (ONC), intravitreal PNG, and intravitreal MnCl(2) injection (150 nmol) at 0 and 20 days post lesion (dpl). MEMRI and echo-planar DTI (DTI-EPI) was obtained of noninjured ON one day after intravitreal MnCl(2) injection, and at 1 and 21 dpl after ONC, intravitreal PNG, and intravitreal MnCl(2) injections given at 0 and 20 dpl. GAP-43 immunohistochemistry was performed after the last MRI. RESULTS: ONC reduced RGC density in retina by 94% at 21 dpl compared to noninjured ON without MnCl(2) injections. Both intravitreal PNG and intravitreal MnCl(2) injections improved RGC survival in retina, which was reduced by 90% (ONC+MnCl(2)), 82% (ONC+PNG), and 74% (ONC+PNG+MnCl(2)) compared to noninjured ON. DTI-derived parameters (fractional anisotropy [FA], mean diffusivity, axial diffusivity lambda( parallel), and radial diffusivity lambda( perpendicular)) were unaffected by the presence of Mn(2+) in the ON. At 1 dpl, CNR(MEMRI) and lambda( parallel) were reduced at the injury site, while at 21 dpl they were increased at the injury site compared to values measured at 1 dpl. GAP-43 immunoreactive axons were present in the ON distal to the ONC injury site. CONCLUSION: MEMRI and DTI enabled detection of functional and structural degradation after rat ON injury, and there was correlation between the MRI-derived and immunohistochemical measures of axon regeneration.

Manganese-enhanced MRI of the rat visual pathway: acute neural toxicity, contrast enhancement, axon resolution, axonal transport, and clearance of Mn(2+).

PURPOSE: To provide dose-response data for the safe and effective use of MnCl(2) for manganese (Mn(2+)) -enhanced MRI (MEMRI) of the visual pathway. MATERIALS AND METHODS: Retinal ganglion cell (RGC) toxicity, CNR in MEMRI, axon density resolution for MEMRI, mode of axonal transport and clearance of Mn(2+) from the vitreous after ivit were investigated. After 0, 30, 150, 300, 1500, and 3000 nmol ivit MnCl(2), neural toxicity was measured by counting surviving RGC back-filled with FluroGold (FG), CNR of the vitreous body and visual pathway by three-dimensional (3D) MEMRI, resolution of ON axon density by correlating CNR with axon density, and axonal transport of Mn(2+) by studying CNR in 3D MEMRI of the ON after ion of 200 nmol MnCl(2). RESULTS: There were no changes in RGC density after ivit MnCl(2) 0 were recorded distally from the ion site, but there was no signal in the retina. At ivit doses >1500 nmol, clearance from the vitreous body was impaired. CONCLUSION: The optimal dose for MEMRI of the rat visual pathway was found to be 150-300 nmol ivit MnCl(2). Higher doses are toxic, causing RGC death, impair active clearance from the vitreous, and loss of Mn(2+) enhancement throughout the visual pathway. Mn(2+) traffic within RGC axons is mediated mainly by anterograde transport.

Mapping the primary motor cortex in healthy subjects and patients with peri-rolandic brain lesions before neurosurgery.

OBJECTIVE: The aim of this study was to establish a robust set of motor tasks that could be used to functionally delineate the motor cortex with blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) at 3 T and produce precise functional maps for pre-operative planning and functional neuronavigation. METHOD: Twelve male and four female control subjects were recruited for this study which examined six different motor tasks. Finger-, tongue-, lip- and toe-movements, as well as isometric upper arm- and thigh-contraction tasks were conducted during separate scans on a 3 T MRI scanner. Furthermore, patients that previously had undergone similar motor tasks were reviewed, to evaluate whether this set of tasks was able to be adopted for use in a population of patients with brain lesions. RESULTS: The results of this study indicated that the finger-, toe- and tongue-motor tasks were the most robust in identifying their respective primary motor area. Moreover, all three tasks activated regions at regular intervals along the convexity of the hemisphere, making it possible to functionally delineate the primary motor cortex in both healthy subjects and patients. DISCUSSION: The motor tasks described in this study (toe, finger and tongue) were effective at localizing the primary motor cortex for the purposes of neurosurgical planning. These three tasks produced the highest success rate and resulted in activations at regular intervals along the convexity of the hemisphere, allowing the delineation of the entire motor strip even in the presence of edema and anatomical distortions.