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Patients with brain cancers including medulloblastoma lack treatments that are effective long‐term and without side effects. In this study, a multifunctional fluoropolymer‐engineered iron oxide nanoparticle gene‐therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum. The blood‐brain barrier (BBB) tailored system demonstrates enhanced BBB penetration, facilitates delivery of functionally active siRNA to medulloblastoma cells, and delivers a significant, almost complete block in protein expression within an in vitro extracellular acidic environment (pH 6.7) – as favored by most cancer cells. In vivo, it effectively crosses an intact BBB, provides contrast for magnetic resonance imaging (MRI), and delivers siRNA capable of slowing tumor growth without causing signs of toxicity – meaning it possesses a safe theranostic function. The pioneering methodology applied shows significant promise in the advancement of brain and tumor microenvironment‐focused MRI‐siRNA theranostics for the better treatment and diagnosis of medulloblastoma. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease involving demyelination and axonal damage in the central nervous system (CNS). In this study, we investigated pathological changes in the lumbar spinal cord of C57BL/6 mice induced with progressive experimental autoimmune encephalomyelitis (EAE) disease using 9.4‐T magnetic resonance imaging (MRI). Multiparametric MRI measurements including MR spectroscopy, diffusion tensor imaging (DTI) and volumetric analyses were applied to detect metabolic changes in the CNS of EAE mice. Compared with healthy mice, EAE mice showed a significant reduction in N‐acetyl aspartate and increases in choline, glycine, taurine and lactate. DTI revealed a significant reduction in fractional anisotropy and axial diffusivity and an increase in radial diffusivity in the lumbar spinal cord white matter (WM), while in the grey matter (GM), fractional anisotropy increased. High‐resolution structural imaging also revealed lumbar spinal cord WM hypertrophy and GM atrophy. Importantly, these MRI changes were strongly correlated with EAE disease scoring and pathological changes in the lumbar (L2–L6), particularly WM demyelination lesions and aggregation of immune cells (microglia/macrophages and astrocytes) in this region. This study identified changes in MRI biomarker signatures that can be useful for evaluating the efficacy of novel drugs using EAE models in vivo. [ABSTRACT FROM AUTHOR]

Purpose: To compare mono- and bi-exponential relaxation model equations to discriminate between normal and fatty liver disease.Materials and Methods: Six rats on a choline deficient amino acid modified (CDAA) diet and six on normal chow were studied. Multiple spin echo images with increasing echo times (TEs) were collected at 9.4T. Pixel-wise T2 maps were generated using mono-exponential decay function to calculate T2M , and a bi-exponential to calculate, short T2 component (T2S ), long T2 component (T2L ), and fractions of these components (ρS , ρL ), respectively. Statistical F-tests and Akaike's information criterion (AIC) were used to assess the relative performance of the two models.Results: F-test and AIC showed that in the CDAA group, T2 bi-exponential model described the signal of T2 weighted imaging of the liver better than the mono-exponential model. Controls were best described by the mono-exponential model. Mean values for T2M , T2L , T2S , ρS , ρL were 31.2 ± 0.7 ms, 72.8 ± 3.3 ms, 8.2 ± 0.6 ms,71.2 ± 2.1%, 30.4 ± 1.3%, respectively, in CDAA rats, compared with 18.8 ± 0.5 ms, 32.3 ± 0.7 ms, 9.2 ± 1.8 ms, 79 ± 2%, 21.0 ± 1.1% in controls.Conclusion: In the fatty liver of CDAA rats we have shown that T2 weighted images fit the bi-exponential model better than mono-exponential decays thus providing a better description of the data.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:468-476. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the microscopic diffusion properties of formalin-fixed breast tissue. Methods: Diffusion microimaging was performed at 16.4T with 40-mm isotropic voxels on two normal and two cancer tissue samples from four patients. Results were correlated with histology of the samples. Results: Diffusion-weighted images and mean diffusivity maps demonstrated distinct diffusivity differences between breast tissue components. Mean diffusivity (MD) in normal tissue was 0.59±0.24 mm2/ms for gland lobule (voxels containing epithelium and intralobular stroma) and 1.23±0.34 mm2/ms for interlobular fibrous stroma. In the cancer samples, MD=0.45±0.23 mm2/ms for invasive ductal carcinoma (voxels contain epithelium and intralobular stroma) and 0.61±0.35 mm2/ms for ductal carcinoma in situ. There were significant MD differences between all tissue components (P<0.005), except between gland lobule and ductal carcinoma in situ (P=0.71). The low diffusivity of epithelium-rich cancer tissue and of normal epithelium relative to its supporting fibrous stroma was similar to that reported for prostate tissue and the esophageal wall. Conclusion: Diffusion microimaging demonstrates distinct diffusivity differences between breast tissue glandular structures. Low diffusivity may be a distinctive feature of mammalian epithelia. [ABSTRACT FROM AUTHOR]

Introduction Vertebral body fat fraction ( FF) has been found to vary between lumbar vertebrae using magnetic resonance spectroscopy ( MRS). We aim to more quickly assess a larger number of adjacent vertebrae using a single T2-weighted iterative decomposition of water and fat with echo asymmetry and least-squares estimation ( IDEAL) sequence. Methods Five men had dual-energy X-ray absorptometry ( DEXA) and 1.5- T MR scans performed. MRS was performed at L3, and a sagittal IDEAL sequence was also performed, resulting in separate fat-only and water-only readings from T10 to S2. For the IDEAL measurements, two independent observers followed a set reading protocol, with five observations each per vertebra. Intra- and interobserver variability were assessed as deviations from the mean within and between observers, respectively. Results For FF measurements there was limited intra-observer variation, with observers being on average within 3.4% of the pooled mean value. Similarly, there was good interobserver agreement, with an average variation of 2.1%. All men showed a reduction in FF of 1.6-7% between L5 and S1. Otherwise, there was a trend of increasing FF moving inferiorly from T10 to S2. This averaged 2.7% per vertebra (range 1.1-3.8%) and may not have been dependent on MRS-measured FF at the L3 level. There was poor correlation between MRS-measured FF at L2-4 and bone mineral density measured using DEXA ( R2 = 0.06). Conclusion IDEAL measurements are generally reproducible between observers following a set protocol. There appears to be a gradient in FF moving from T10 to S2, with S1 showing a consistent decrease. This variation may better describe overall marrow function than a single-vertebra reading. [ABSTRACT FROM AUTHOR]

The main aim of this study was to employ high-resolution MRI to investigate the spatiotemporal development of pathological features associated with contusive spinal cord injury (SCI) in mice. Experimental mice were subjected to either sham surgery or moderate contusive SCI. A 16.4-T small-animal MR system was employed for nondestructive imaging of post-mortem, fixed spinal cord specimens at the subacute (7 days) and more chronic (28-35 days) stages post-injury. Routine histological techniques were used for subsequent investigation of the observed neuropathology at the microscopic level. The central core of the lesion appeared as a dark hypo-intense area on MR images at all time points investigated. Small focal hypo-intense spots were also observed spreading through the dorsal funiculi proximal and distal to the site of impact, an area that is known to undergo gliosis and Wallerian degeneration in response to injury. Histological examination revealed these hypo-intense spots to be high in iron content as determined by Prussian blue staining. Quantitative image analysis confirmed the increased presence of iron deposits at all post-injury time points investigated ( p < 0.05). Distant iron deposits were also detectable through live imaging without the use of contrast-enhancing agents, enabling the longitudinal investigation of this pathology in individual animals. Further immunohistochemical evaluation showed that intracellular iron deposits localised to macrophages/microglia, astrocytes and oligodendrocytes in the subacute phase of SCI, but predominantly to glial fibrillary acidic protein-positive, CC-1-positive astrocytes at later stages of recovery. Progressive, widespread intracellular iron accumulation is thus a normal feature of SCI in mice, and high-resolution MRI can be effectively used to detect and monitor these neuropathological changes with time. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Diffusion tensor microimaging at 16.4 T with 40 μm isotropic voxels was used to investigate anisotropic water diffusion in prostate tissue at spatial resolution approaching the cellular scale. Nine normal glandular tissue samples were collected from the peripheral zone of six formalin fixed radical prostatectomy specimens. Fibromuscular stromal tissue exhibited microscopic diffusion anisotropy (mean fractional anisotropy range 0.47-0.66) significantly higher ( P < 0.01, Student's t-test) than in epithelium-containing voxels (mean fractional anisotropy range 0.31-0.54) in six of the seven normal tissue samples in which both compartments could be measured. Fiber tracking demonstrated principle stromal fiber directions consistent with myocyte orientation seen on light microscopy of the same sample. Diffusion tensor microimaging may be valuable for investigation of variable results from attempts to measure diffusion anisotropy in the prostate in vivo. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Transgenic mice overexpressing chicken Ski (c-Ski) have marked decrease in adipose mass with skeletal muscle hypertrophy. Recent evidence indicates a role for c-Ski in lipogenesis and energy expenditure. In the present study, wild type (WT) and c-Ski mice were challenged on a high-fat (HF) diet to determine whether c-Ski mice were resistant to diet-induced obesity. During the HF feeding WT mice gained significantly more weight than chow-fed animals, while c-Ski mice were partially resistant to the effects of the HF diet on weight. Body composition analysis confirmed the decreased adipose mass in c-Ski mice compared to WT mice. c-Ski mice possess a similar metabolic rate and level of food consumption to WT littermates, despite lower activity levels and on chow diet show mild glucose intolerance relative to WT littermates. On HF diet, glucose tolerance surprisingly remained unchanged in c-Ski mice, while it became worse in WT mice. Skeletal muscle of c-Ski mice exhibit impaired insulin-stimulated Akt phosphorylation and glucose uptake. In concordance, gene expression profiling of skeletal muscle of chow and HF-fed mice indicated that Ski suppresses gene expression associated with insulin signaling and glucose uptake and alters gene pathways involved in myogenesis and adipogenesis. In conclusion, c-Ski mice are partially resistant to diet-induced obesity and display aberrant insulin signaling and glucose homeostasis which is associated with alterations in gene expression that inhibit lipogenesis and insulin signaling. These results suggest Ski plays a major role in skeletal muscle metabolism and adipogenesis and hence influences risk of obesity and diabetes. [ABSTRACT FROM AUTHOR]

Magnetic resonance microimaging was used to measure diffusion decay over an extended b-factor range in a formalin-fixed normal prostate sample and a Gleason pattern 3+4 cancer tissue sample. The coefficients of biexponential fits to diffusion decay data from 1600 voxels of dimension 160 × 160 × 160 μm3 in each sample were correlated with underlying epithelial and stromal compartment partial volumes estimated from high-resolution apparent diffusion coefficient (ADC) data (40 × 40 × 40 μm3 voxels) from the same tissue. In the normal tissue sample, the signal fractions of the low and high ADC components of the biexponential fits correlated linearly with partial volumes of epithelial tissue ( R2 = 0.6) and stromal tissue ( R2 = 0.5), respectively. Similar but weaker correlations were observed in the cancer sample. Epithelium-containing high spatial resolution voxels appeared to be composed of ∼60% low ADC and ∼40% high ADC component. Stromal voxels appeared to be composed of ∼20% low ADC and ∼80% high ADC component. This preliminary report suggests that distinctly different diffusion properties in microscopically adjacent cell types contribute to the multiexponential diffusion decay phenomenon in prostate tissue. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

MR microimaging at 16.4 T with 40-μm isotropic voxels was used to investigate compartmentation of water diffusion in formalin-fixed prostate tissue. Ten tissue samples (∼ 28 mm3 each) from five organs were imaged. The mean diffusivity of epithelial, stromal, and ductal/acinar compartments was estimated by two methods: (1) manual region of interest selection and (2) Gaussian fitting of voxel diffusivity histograms. For the region of interest-method, the means of the tissue sample compartment diffusivities were significantly different ( P < 0.001): 0.54 ± 0.05 μm2/ms for epithelium-containing voxels, 0.91 ± 0.17 μm2/ms for stroma, and 2.20 ± 0.04 μm2/ms for saline-filled ducts. The means from the histogram method were also significantly different ( P < 0.001): 0.45 ± 0.08 μm2/ms for epithelium-containing voxels, 0.83 ± 0.16 μm2/ms for stroma, 2.21 ± 0.02 μm2/ms for duct. Estimated partial volumes of epithelial, stromal, and ductal/acinar compartments in a 'tissue only' subvolume of each sample were significantly different ( P < 0.02) between cancer and normal tissue for all three compartments. It is concluded that the negative correlation between apparent diffusion coefficient and cancer Gleason grade observed in vivo results from an increase of partial volume of epithelial tissue and concomitant decrease of stromal tissue and ductal space. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Diffusion tensor microimaging was used to investigate the water diffusion properties of formalin-fixed prostate tissue at spatial resolution approaching the cellular scale. Diffusion tensor microimaging was performed at 16.4 T with 40 μm isotropic voxels. Diffusion tensor microimaging clearly demonstrated distinct microscopic diffusion environments and tissue architecture consistent with that seen on light microscopy of the same tissue. The most restricted diffusion environment is the secretory epithelial cell layer (voxel bulk mean diffusivity, D = 0.4 ± 0.1 × 10 mm/sec). Diffusion in the fibromuscular stromal matrix is relatively less restricted ( D = 0.7 ± 0.1 × 10 mm/sec). In tumor tissue (Gleason pattern 4+4) distinct glandular and ductal structures are absent in the diffusion-weighted images and diffusivity is low ( D = 0.5 ± 0.1 × 10 mm/sec). Distinct stromal and epithelial diffusion compartments are the most likely origin of biexponential diffusion decay observed in vivo. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article focuses on the possibility that enhancement of the in-plane image may be obtained through a change of the demodulation frequency in magnetic resonance images (MRI) with low resolutions. It discusses how image enhancement is obtained from low-resolution images during the application of signal processing theory in phantom experiments. It states the use of Fourier data and pixel size to achieve the maximum resolution for MRI.

Magnetic resonance histology (MRH) has become a widespread tool to examine brain morphology in situ or ex vivo. Samples are routinely fixed and stained to allow for longer scan times with increased contrast and resolution. Although the zebrafish is an important model for neuroscience, to date most MRH studies have focused almost exclusively on mice. In this paper, we examined, for the first time, the zebrafish brain using MRH. We compared a range of fixatives, contrast agents, and fixation/staining durations to determine optimal imaging of the zebrafish brain. By quantifying the T1, T2, and T2* relaxation values, we demonstrated that ethanol and potassium permanganate are unviable for imaging and significant differences exist between mono and di-aldehydes. Furthermore, we compared two commercially available gadolinium-based contrast agents, Magnevist® and Optimark®, at five different concentrations. For both contrast agents, a concentration of 0.5% was determined to be ideal as it significantly shortened the T1 but maintained a relatively long T2 and T2*. Subsequently, we analyzed the duration of fixation/staining and established a period of 12 h, which best minimized T1 values but maintained T2 and T2* values. Finally, using this optimized fixation and staining protocol, we performed a gradient-echo T2*-weighted imaging to obtain an image set of the adult zebrafish brain at an isotropic resolution of 10 µm. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose To compare noninvasive MRI and magnetic resonance spectroscopy (MRS) methods with liver biopsy to quantify liver fat content. Materials and Methods Quantification of liver fat was compared by liver biopsy, proton MRS, and MRI using in-phase/out-of-phase (IP/OP) and plus/minus fat saturation (±FS) techniques. The reproducibility of each MR measure was also determined. An additional group of overweight patients with steatosis underwent hepatic MRI and MRS before and after a six-month weight-loss program. Results A close correlation was demonstrated between histological assessment of steatosis and measurement of intrahepatocellular lipid (IHCL) by MRS (rs = 0.928, P < 0.0001) and MRI (IP/OP rs = 0.942, P < 0.0001; FS rs = 0.935, P < 0.0001). Following weight reduction, four of five patients with >5% weight loss had a decrease in IHCL of ≥50%. Conclusion These findings suggest that standard MRI protocols provide a rapid, safe, and quantitative assessment of hepatic steatosis. This is important because MRS is not available on all clinical MRI systems. This will enable noninvasive monitoring of the effects of interventions such as weight loss or pharmacotherapy in patients with fatty liver diseases. J. Magn. Reson. Imaging 2008;28:937-945. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background and objective: MRI of the lung using hyperpolarized helium as an inhaled contrast agent has important research applications and clinical potential. Owing to the limited availability of hyperpolarized helium, this type of imaging has not been performed in the human lung outside of North America or Europe. The objective of this study was to test the feasibility of imaging human lungs in Australia using hyperpolarized helium gas imported from Germany. Methods: A Bruker 2-Tesla whole-body magnetic resonance scanner located in Brisbane, Australia was adapted with a helium-3 radiofrequency transceiver coil. Helium-3 was hyperpolarized to 72% in Mainz, Germany and airfreighted to Brisbane. The time taken for the journey was 32 h and scanning was performed 36–40 h after departure from Mainz, with an estimated polarization level of 44%. Procedures were developed to transfer 300 mL of the hyperpolarized helium to Tedlar bags filled with 700 mL of nitrogen. Healthy volunteers inhaled the 1 L helium/nitrogen mixture from FRC, and imaging was performed with a 10 s breathhold. Results: Imaging showed very detailed and even ventilation of all regions of the lung with a good signal-to-noise ratio. No adverse effects of inhaling the gas mixture were noted. Conclusions: This report of MRI of the human lung using hyperpolarized helium demonstrates the feasibility of long distance gas transport from Germany to Australia. This will help to facilitate research and clinical application of this innovative functional lung imaging technique. [ABSTRACT FROM AUTHOR]

Spatial encoding in MR techniques is achieved by sampling the signal as a function of time in the presence of a magnetic field gradient. The gradients are assumed to generate a linear magnetic field gradient, and typical image reconstruction relies upon this approximation. However, high-speed gradients in the current generation of MRI scanners often sacrifice linearity for improvements in speed. Such nonlinearity results in distorted images. The problem is presented in terms of first principles, and a correction method based on a gradient field spherical harmonic expansion is proposed. In our case, the amount of distortion measured within a typical field of view (FOV) required for head imaging is sufficiently large that without the use of some distortion correction technique, the images would be of limited use for stereotaxy or longitudinal studies, where precise volumetric information is required. Magn Reson Med 52:115-122, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]