Improving FLAIR SAR efficiency at 7T by adaptive tailoring of adiabatic pulse power through deep learning B1+ estimation.

PURPOSE: The purpose of this study is to demonstrate a method for specific absorption rate (SAR) reduction for 2D T2 -FLAIR MRI sequences at 7 T by predicting the required adiabatic radiofrequency (RF) pulse power and scaling the RF amplitude in a slice-wise fashion. METHODS: We used a time-resampled frequency-offset corrected inversion (TR-FOCI) adiabatic pulse for spin inversion in a T2 -FLAIR sequence to improve B1+ homogeneity and calculated the pulse power required for adiabaticity slice-by-slice to minimize the SAR. Drawing on the implicit B1+ inhomogeneity in a standard localizer scan, we acquired 3D AutoAlign localizers and SA2RAGE B1+ maps in 28 volunteers. Then, we trained a convolutional neural network (CNN) to estimate the B1+ profile from the localizers and calculated pulse scale factors for each slice. We assessed the predicted B1+ profiles and the effect of scaled pulse amplitudes on the FLAIR inversion efficiency in oblique transverse, sagittal, and coronal orientations. RESULTS: The predicted B1+ amplitude maps matched the measured ones with a mean difference of 9.5% across all slices and participants. The slice-by-slice scaling of the TR-FOCI inversion pulse was most effective in oblique transverse orientation and resulted in a 1 min and 30 s reduction in SAR induced delay time while delivering identical image quality. CONCLUSION: We propose a SAR reduction technique based on the estimation of B1+ profiles from standard localizer scans using a CNN and show that scaling the inversion pulse power slice-by-slice for FLAIR sequences at 7T reduces SAR and scan time without compromising image quality.

Enhanced Dopamine in Prodromal Schizophrenia (EDiPS): a new animal model of relevance to schizophrenia.

One of the most robust neurochemical abnormalities reported in patients living with schizophrenia is an increase in dopamine (DA) synthesis and release in the dorsal striatum (DS). Importantly, it appears that this increase progresses as a patient transitions from a prodromal stage to the clinical diagnosis of schizophrenia. Here we have recreated this pathophysiology in an animal model by increasing the capacity for DA synthesis preferentially within the DS. To achieve this we administer a genetic construct containing the rate-limiting enzymes in DA synthesis-tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) (packaged within an adeno-associated virus)-into the substantia nigra pars compacta (SNpc) of adolescent animals. We refer to this model as "Enhanced Dopamine in Prodromal Schizophrenia" (EDiPS). We first confirmed that the TH enzyme is preferentially increased in the DS. As adults, EDiPS animals release significantly more DA in the DS following a low dose of amphetamine (AMPH), have increased AMPH-induced hyperlocomotion and show deficits in pre-pulse inhibition (PPI). The glutamatergic response to AMPH is also altered, again in the DS. EDiPS represents an ideal experimental platform to (a) understand how a preferential increase in DA synthesis capacity in the DS relates to "positive" symptoms in schizophrenia; (b) understand how manipulation of DS DA may influence other neurotransmitter systems shown to be altered in patients with schizophrenia; (c) allow researchers to follow an "at risk"-like disease course from adolescence to adulthood; and (d) ultimately allow trials of putative prophylactic agents to prevent disease onset in vulnerable populations.

Bacillus anthracis Protective Antigen Shows High Specificity for a UV Induced Mouse Model of Cutaneous Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) accounts for the majority of non-melanoma skin cancer related deaths, particularly in immunosuppressed persons. Identification of biomarkers that could be used to identify or treat SCC would be of significant benefit. The anthrax toxin receptors, Tumor Endothelial Marker 8 (TEM8) and Capillary Morphogenesis Gene 2 (CMG2), are endothelial receptors involved in extracellular matrix homeostasis and angiogenesis that are selectively upregulated on numerous tumors. One method of targeting these receptors is Protective Antigen (PA), a protein produced by B. anthracis that mediates binding and translocation of anthrax toxins into cells. PA targeted toxins have been demonstrated to selectively inhibit tumor growth and angiogenesis, but tumor selectivity of PA is currently unknown. In this work fluorescently labeled PA was shown to maintain receptor dependent binding and internalization in vitro. Utilizing a human papillomavirus transgenic mouse model that develops cutaneous SCC in response to ultraviolet irradiation we identified tumor uptake of PA in vivo. The intravenously administered PA resulted in tumor specific localization, with exclusive tumor detection 24 h post injection. Ex vivo analysis identified significantly higher fluorescence in the tumor compared to adjacent healthy tissue and major clearance organs, demonstrating low non-specific uptake and rapid clearance. While both TEM8 and CMG2 were observed to be overexpressed in SCC tumor sections compared to control skin, the intravenously administered PA was primarily co-localized with TEM8. These results suggest that PA could be systemically administered for rapid identification of cutaneous SCC, with potential for further therapeutic development.

MR-based electrical property tomography using a modified finite difference scheme.

Magnetic resonance electrical property tomography (MR-EPT) reconstructs electrical properties (EPs) from measured magnetic fields in magnetic resonance imaging (MRI) systems. In this study, an MR-EPT method was proposed that utilized a new finite difference approximation of the involved differential wave equation. Compared with existing MR-EPT approaches, the construction of the system matrix involves applying the first derivative twice based on a larger number of neighbouring finite-difference grids, which is different from a standard Laplacian operator on a regular grid structure, leading to a better conditioned linear inverse problem. With improved noise robustness, more faithful EPs can be obtained by the proposed method, particularly at tissue boundaries and regions with a poorly measured magnetic field (low signal-to-noise ratio). Numerical simulations with a specially designed multi-slice phantom and an anatomically accurate head model (Duke) have demonstrated that the proposed method can provide a more faithful reconstruction of EPs compared to existing methods, which usually offer unreliable solutions associated with traditional finite difference approximation of the central wave equation and unrealistic assumptions. Experiments on a 9.4 T MRI system have been conducted to validate the simulations.

Magnetic resonance spin-spin relaxation time estimation in a rat model of fatty liver disease.

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.

Radial magnetic resonance imaging (MRI) using a rotating radiofrequency (RF) coil at 9.4 T.

The rotating radiofrequency coil (RRFC) has been developed recently as an alternative approach to multi-channel phased-array coils. The single-element RRFC avoids inter-channel coupling and allows a larger coil element with better B1 field penetration when compared with an array counterpart. However, dedicated image reconstruction algorithms require accurate estimation of temporally varying coil sensitivities to remove artefacts caused by coil rotation. Various methods have been developed to estimate unknown sensitivity profiles from a few experimentally measured sensitivity maps, but these methods become problematic when the RRFC is used as a transceiver coil. In this work, a novel and practical radial encoding method is introduced for the RRFC to facilitate image reconstruction without the measurement or estimation of rotation-dependent sensitivity profiles. Theoretical analyses suggest that the rotation-dependent sensitivities of the RRFC can be used to create a uniform profile with careful choice of sampling positions and imaging parameters. To test this new imaging method, dedicated electronics were designed and built to control the RRFC speed and hence positions in synchrony with imaging parameters. High-quality phantom and animal images acquired on a 9.4 T pre-clinical scanner demonstrate the feasibility and potential of this new RRFC method.

Image Reconstruction for a Rotating Radiofrequency Coil (RRFC) Using Self-Calibrated Sensitivity From Radial Sampling.

The purpose of this study was to develop a practical magnetic resonance imaging (MRI) scheme for the latest rotating radiofrequency coil (RRFC) design at 9.4 T. The new prototype RRFC was integrated with an optical sensor to facilitate recording of its angular positions relative to the sequence timing. In imaging, the RRFC was used together with radial k-space trajectories. To recover the image, the radial spokes were grouped according to the coil locations. Using an Eigen-decomposition approach, an array of location-dependent sensitivity maps was extracted from the central regions of the segmented k-space, enabling parallel-imaging techniques for image recovery in a straightforward manner. When the RRFC angular velocity is carefully designed and accurately controlled according to the sequence timing, the encoding by means of varying RRFC sensitivity maps can be accurately calibrated for a faithful image recovery. Approximations were made to counteract the variations of the RRFC angular velocity, providing successful image reconstruction at 9.4 T. The current study demonstrated a new and practical imaging scheme for RRFC-MRI. It is able to extract the temporally varying sensitivity maps retrospectively from the k-space acquisition itself, without resorting to electromagnetic simulation or numerical interpolation. The proposed imaging scheme and the supporting engineering solutions of the RRFC prototype enable accurate image reconstructions. These new developments pave the way for routine applications of the RRFC, and bode well for its further development in providing simultaneous multinuclear imaging by incorporating, for example, independent X-nuclear coil elements into the rotating structure.

Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is due to primary hypothyroidism.

BACKGROUND: Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were (≈) 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine-induced salivary flow and salivary α-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight) and salivary gland hypofunction (salivary flow, salivary α-amylase activity, histological changes) were restored to normal or near normal by thyroid hormone supplementation. CONCLUSIONS/SIGNIFICANCE: Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.

Brain injury: neuro-inflammation, cognitive deficit, and magnetic resonance imaging in a model of blast induced traumatic brain injury.

Blast wave-induced traumatic injury from terrorist explosive devices can occur at any time in either military or civilian environments. To date, little work has focused on the central nervous system response to a non-penetrating blast injury. We have evaluated the effect of a single 80-psi blast-overpressure wave in a rat model. Histological and immunochemical studies showed an early inflammatory response, tissue damage and the initiation of apoptosis. With regard to inflammation, polymorphonuclear leukocytes and lymphocytes infiltrated brain parenchyma within 1 h post-blast. Glial-fibrillary protein, cyclo-oxygenase-2ir, interleukin-1ß and tumor necrosis factor were present by 1 h and remained detectable at three weeks post-injury. High mobility group box-1 protein was detectable at three weeks. With regard to tissue damage, S100ß and 4-hydroxynonenal were present at 1 h and remained detectable at three weeks. Amyloid precursor protein was detectable at three weeks. As for apoptosis, Cleaved Caspase-3 was detectable at three weeks. Morris water maze assessment of cognitive function showed that blast injured animals required significantly more time to reach the platform on day 1 of training and traveled a greater distance to get to the platform on days 1 and 2. Blast-injured animals showed a significant increase in swimming speed (p<0.001), increased total distance traveled (p<0.001) and increased number of entries into the previous quadrant that had contained the escape platform (p<0.05). Magnetic resonance imaging showed hyperintense regions in the somatosensory area within 1 h. T2 relaxation times and apparent diffusion coefficients show increasing trends in both somatosensory and cortical regions. These data indicate an early and lasting response of brain tissue to non-penetrating blast over-pressure injury. This early inflammatory response is indicative of a mild traumatic brain injury. There is evidence of early hippocampal dysfunction.

Metabolic inflexibility and protein lysine acetylation in heart mitochondria of a chronic model of type 1 diabetes.

Diabetic cardiomyopathy refers to the changes in contractility that occur to the diabetic heart that can arise in the absence of vascular disease. Mitochondrial bioenergetic deficits and increased free radical production are pathological hallmarks of diabetic cardiomyopathy, but the mechanisms and causal relationships between mitochondrial deficits and the progression of disease are not understood. We evaluated cardiac mitochondrial function in a rodent model of chronic Type 1 diabetes (OVE26 mice) before the onset of contractility deficits. We found that the most pronounced change in OVE26 heart mitochondria is severe metabolic inflexibility. This inflexibility is characterized by large deficits in mitochondrial respiration measured in the presence of non-fatty acid substrates. Metabolic inflexibility occurred concomitantly with decreased activities of PDH (pyruvate dehydrogenase) and complex II. Hyper-acetylation of protein lysine was also observed. Treatment of control heart mitochondria with acetic anhydride (Ac2O), an acetylating agent, preferentially inhibited respiration by non-fatty acid substrates and increased superoxide production. We have concluded that metabolic inflexibility, induced by discrete enzymatic and molecular changes, including hyper-acetylation of protein lysine residues, precedes mitochondrial defects in a chronic rodent model of Type 1 diabetes.

Utility of nuclear magnetic resonance spectroscopy for pancreatic cancer studies.

OBJECTIVES: The aims of this study were (1) to determine nuclear magnetic resonance spectroscopic characteristics and metabolite profiles of serum samples from patients with pancreatic cancer compared with noncancerous control samples and (2) to ascertain if the accuracy of metabolite identification by 1D spectra can be improved upon by confirmation of spin-system assignment using more sophisticated experiments. METHODS: Nuclear magnetic resonance spectra, including 1D, total correlation spectroscopy, and heteronuclear multiple/single quantum coherence, were obtained from serum samples from patients with pancreatic cancer and control subjects and used to determine serum levels of a range of metabolites. RESULTS: The data show that total choline (P = 0.03), taurine (P = 0.03), and glucose plus triglycerides (P = 0.01) are significantly higher in cancer versus control samples. Also detected were species that could not be individually identified and that were designated UCM (unresolved complex matter). Levels of UCM are significantly higher in subjects with cancer, being almost double those of control samples. CONCLUSIONS: Although metabolites such as lactate, taurine, glucose, choline, and triglycerides can be determined from 1D spectra, accuracy is improved by confirmation of spin-system assignment with total correlation spectroscopy and heteronuclear multiple/single quantum coherence spectral analysis. In addition, we introduce a new metric, UCM, which is at higher concentrations in cancer compared with control samples.

Implementation equations for HS n RF pulses.

Implementation equations for the family of stretched hyperbolic secant (HS(n)) pulses are derived in the linear adiabatic range for inversion of spins. These master equations provide convenience relations for relating the peak amplitude RF(max) of the pulse to the frequency sweep (bwdth) range of the pulse and its duration T(p). The bandwidth of the pulse can also be related to the effective coverage (bw(eff)) of the pulse to a defined or chosen spectral region. The choice of pulse determined by the use of these derived expressions guarantees uniform inversion to a prescribed efficiency across the selected spectral region. The performance of HS(n) pulses in determining the cut-off region between spectral regions was also examined. It is found that beyond a unique T(p)bwdth product no additional gain may be obtained by extending pulse durations for a chosen bwdth of pulse. An example of practical implementation of the inversion pulses is presented for adiabatic decoupling using HS(7) and HS(8) pulses. It is shown that despite added B(1) inhomogeneity in the form of additional amplifier power to 400% from optimal, these pulses can still yield reproducible decoupled spectra.

Magnetic resonance imaging guidance for laser photothermal therapy.

Temperature distribution is a crucial factor in determining the outcome of laser phototherapy in cancer treatment. Magnetic resonance imaging (MRI) is an ideal method for 3-D noninvasive temperature measurement. A 7.1-T MRI was used to determine laser-induced high thermal gradient temperature distribution of target tissue with high spatial resolution. Using a proton density phase shift method, thermal mapping is validated for in vivo thermal measurement with light-absorbing enhancement dye. Tissue-simulating phantom gels, biological tissues, and tumor-bearing animals were used in the experiments. An 805-nm laser was used to irradiate the samples, with laser power in the range of 1 to 3 W. A clear temperature distribution matrix within the target and surrounding tissue was obtained with a specially developed processing algorithm. The temperature mapping showed that the selective laser photothermal effect could result in temperature elevation in a range of 10 to 45 degrees C. The temperature resolution of the measurement was about 0.37 degrees C with 0.4-mm spatial resolution. The results of this study provide in vivo thermal information and future reference for optimizing laser dosage and dye concentration in cancer treatment.

Visualization of the protective ability of a free radical trapping compound against rat C6 and F98 gliomas with diffusion tensor fiber tractography.

PURPOSE: To apply fiber tractography to assess the effect of a possible antiglioma drug, phenyl N-tert-butyl nitrone (PBN), on glioma-affected neuronal fibers. The fiber tractography method was able to differentiate between different tumor types, such as the C6 and F98 rat glioma models. MATERIALS AND METHODS: C6 or F98 cells were intracranially injected into the cortex of male Fischer 344 rats. PBN treatment was initiated before or after cell implantation. Tumor growth was monitored with diffusion tensor imaging (DTI) and fiber tractography using diffusion-weighting gradients in 30 noncolinear directions. RESULTS: Although proton density-weighted (PDw) and T2-weighted (T2w) images did not show any difference between C6 and F98 gliomas without edema, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were able to discriminate between these two tumor models. Fiber tractography was used to visualize C6 glioma-induced ischemia of tumor-surrounding tissues, whereas F98 glioma was found to infiltrate and penetrate into the corpus callosum (CC). During glioma growth, neuronal fibers were found to disappear at the border regions between the tumor and surrounding tissues. PBN treatment was shown to inhibit glioma growth with accompanying changes in the surrounding tissue. CONCLUSION: By noninvasively monitoring the degree of neuronal fiber integrity and connectivity with the use of neuronal fiber tractography, we were able to evaluate the protective effect of PBN against invasive glioma growth in rat brains. PBN provided protection of the neuronal fibers against tumor-induced ischemia and tumor invasion.

Diffusion tensor imaging and fiber tractography of C6 rat glioma.

PURPOSE: To apply diffusion tensor images using 30 noncollinear directions for diffusion-weighted gradient schemes to characterize diffusion tensor imaging (DTI) features associated with C6 glioma-bearing rat brains, and ideally visualize fiber tractography datasets. MATERIALS AND METHODS: Fiber tractographies of normal male Fischer 344 rat brains were constructed from DTI datasets acquired with a 30 noncollinear diffusion gradient scheme. Cultured C6 cell were intracranially injected into the cortex of male Fischer 344 rats. The time course of the tumor growth was monitored with DTI and fiber tractography using diffusion-weighting gradients in 30 noncollinear directions. RESULTS: Fiber tractographies through the corpus callosum (CC) were easily visualized with the 30-direction gradient scheme, and the fiber trajectories of the motor cortex and striatum were well represented in normal rats. Fiber tractography indicated that the neuronal fibers of the CC were compressed or disappeared by growing C6 glioma, which affected surrounding brain tissue. CONCLUSION: We have demonstrated in this study that fiber tractography with the 30 noncollinear diffusion gradient scheme method can be used to help provide a better understanding regarding the influence of a tumor on the surrounding regions of normal brain tissue in vivo.

Chemical speciation by selective heteronuclear single-quantum coherence spectroscopy: determination of double-bond quantity in unsaturated fatty acid compounds.

A method for identifying fatty acid species based on the number of double bonds contained in a lipid molecule is presented. Common to all polyunsaturated fatty acids are two signature resonances at approximately 5.3 and 2.8 ppm in the proton chemical-shift spectrum of NMR. These resonances are from the vinyl and bis-allyl protons, respectively, and, although they can be readily observed by NMR from lipid extracts of biological samples, direct speciation has never been demonstrated by NMR. By modifying a conventional HSQC pulse sequence with a J-pulse on the spin system of the vinyl group (generalized as an IS spin system) at the beginning of the initial polarization transfer period and selectively inverting the 13C (I) spins with a narrowband sech/tanh inversion pulse, the collection of data in both dimensions can be restricted to a narrow slice of the chemical-shift range. The resolution is subsequently determined by digitizer efficiency, and spectra can be collected optimally from within a very narrow 1 x 6 ppm window of the respective proton and carbon chemical-shift ranges. With this modification it is possible to distinguish at least one resonance each from the multiple shifts expected from the indirectly detected nuclei of the fatty acid species, oleic acid, linoleic acid, linolenic acid and arachidonic acid, which contain one, two, three and four double bonds, respectively. This and similar methods of applied selectivity are of potential interest in characterizing speciation in biological samples where mixtures are often encountered and chemical shifts of the same structural group of similar molecules give rise to complicated overlapping resonances but are important for diagnosis of disease processes such as cancer.

In vivo detection of c-MET expression in a rat hepatocarcinogenesis model using molecularly targeted magnetic resonance imaging.

The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA)-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO)-anti-c-MET molecularly targeted magnetic resonance imaging (MRI) contrast agent. SPIO-anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T(2) values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3) cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO-anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI).

BACKGROUND: Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. METHODS: Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19-25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. RESULTS: After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. CONCLUSION: Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy.

MRI compatible electrodes for the induction of amygdala kindling in rats.

The rat electrical kindling model has been widely utilized in epilepsy research. This study aimed to identify the optimum "MRI compatible" bipolar stimulating and recording electrodes to enable serial MRI acquisition in this model. Two types of custom-made electrodes (gold and carbon) were compared with commercial platinum-iridium alloy electrodes for suitability based on size, effect on image quality and kindling induction. The custom-made gold electrodes, based on these parameters, were found to be most suitable. These electrodes enable the study of epileptogenesis utilizing MRI in this model of temporal lobe epilepsy (TLE).

Hippocampal T2 signal change during amygdala kindling epileptogenesis.

PURPOSE: The rat electrical amygdala kindling model is one of the most widely studied animal models of temporal lobe epilepsy (TLE); however, the processes underlying epileptogenesis in this model remain incompletely understood. Magnetic resonance imaging (MRI) is a powerful method to investigate epileptogenesis, allowing serial imaging of associated structural and functional changes in vivo. Here we report on the results of serial MRI acquisitions during epileptogenesis in this model. METHODS: Serial T2-weighted MR images were acquired before, during, and after the induction of kindling, to investigate the development and progression of imaging abnormalities. RESULTS: T2-weighted acquisitions demonstrated the development of regions of increased signal in the rostral ipsilateral regions of CA1 and dentate gyrus in kindled (five of seven) but not in control rats (p < 0.05). Quantification of the T2 signal demonstrated a significant increase in kindled animals when compared with controls, 2 weeks after kindling ceased, in the ipsilateral hippocampus and the hippocampal sub regions of CA1 and the dentate gyrus (p < 0.05). No significant difference was observed in hippocampal volumes between kindled or control animals at any of the times. CONCLUSIONS: The results of this study validate a method for acquiring serial MRI during amygdala kindling and demonstrate the induction of T2 signal abnormalities in focal regions of the hippocampus. These regions may be important sites for the neurobiologic changes that contribute to epileptogenesis in this model.