Biomedical subjects

Mehmet Bilgen

Publications and source records attributed to Mehmet Bilgen.

At least 19 recordsLinked to original sources

PubMed2006

Imaging corticospinal tract connectivity in injured rat spinal cord using manganese-enhanced MRI.

BACKGROUND: Manganese-enhanced MRI (MEI) offers a novel neuroimaging modality to trace corticospinal tract (CST) in live animals. This paper expands this capability further and tests the utility of MEI to image axonal fiber connectivity in CST of injured spinal cord (SC). METHODS: A rat was injured at the thoracic T4 level of the SC. The CST was labeled with manganese (Mn) injected intracortically at two weeks post injury. Next day, the injured SC was imaged using MEI and diffusion tensor imaging (DTI) modalities. RESULTS: In vivo MEI data obtained from cervical SC confirmed that CST was successfully labeled with Mn. Ex vivo MEI data obtained from excised SC depicted Mn labeling of the CST in SC sections caudal to the lesion, which meant that Mn was transported through the injury, possibly mediated by viable CST fibers present at the injury site. Examining the ex vivo data from the injury epicenter closely revealed a thin strip of signal enhancement located ventrally between the dorsal horns. This enhancement was presumably associated with the Mn accumulation in these intact fibers projecting caudally as part of the CST. Additional measurements with DTI supported this view. CONCLUSION: Combining these preliminary results collectively demonstrated the feasibility of imaging fiber connectivity in experimentally injured SC using MEI. This approach may play important role in future investigations aimed at understanding the neuroplasticity in experimental SCI research.

Journal Article↗

PubMed2006

Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats.

Sympathetic hyperinnervation occurs in human ventricular tissue after myocardial infarction and may contribute to arrhythmias. Aberrant sympathetic sprouting is associated with elevated nerve growth factor (NGF) in many contexts, including ventricular hyperinnervation. However, it is unclear whether cardiomyocytes or other cell types are responsible for increased NGF synthesis. In this study, left coronary arteries were ligated and ventricular tissue examined in rats 1-28 days post-infarction. Infarct and peri-infarct tissue was essentially devoid of sensory and parasympathetic nerves at all time points. However, areas of increased sympathetic nerve density were observed in the peri-infarct zone between post-ligation days 4-14. Hyperinnervation occurred in regions containing accumulations of macrophages and myofibroblasts. To assess whether these inflammatory cells synthesize NGF, sections were processed for NGF in situ hybridization and immunohistochemistry. Both macrophage1 antigen-positive macrophages and alpha-smooth muscle actin-immunoreactive myofibroblasts expressed NGF in areas where they were closely proximate to sympathetic nerves. To investigate whether NGF produced by peri-infarct cells induces sympathetic outgrowth, we co-cultured adult sympathetic ganglia with peri-infarct explants. Neurite outgrowth from sympathetic ganglia was significantly greater at post-ligation days 7-14 as compared to control tissue. Addition of an NGF function-blocking antibody prevented the increased neurite outgrowth induced by peri-infarct tissue. These findings provide evidence that inflammatory cell NGF synthesis plays a causal role in sympathetic hyperinnervation following myocardial infarction.

Analysis of Variance↗

PubMed2006

Exercise training improves cardiac performance in diabetes: in vivo demonstration with quantitative cine-MRI analyses.

Diabetic cardiomyopathy is a distinct myocardial complication of the catabolic state of untreated insulin-dependent diabetes mellitus in the streptozotocin-induced diabetic rat. Exercise training has long been utilized as an effective adjunct to pharmacotherapy in the management of the diabetic heart. However, the in vivo functional benefit(s) of the training programs on cardiac cycle events in diabetes are poorly understood. In this study, we used three groups of Sprague-Dawley rats (sedentary control, sedentary diabetic, and exercised diabetic) to assess the effects of endurance training on the left ventricular (LV) cardiac cycle events in diabetes. At the end of 9 wk of exercise training, noninvasive cardiac functional evaluation was performed by using high-resolution magnetic resonance imaging (9.4 T). An ECG-gated cine imaging protocol was used to capture the LV cardiac cycle events through 10 equally incremented phases. The cardiac cycle phase volumetric profiles showed favorable functional changes in exercised diabetic group, including a prevention of decreased end-diastolic volume and attenuation of increased end-systolic volume that accompanies sedentary diabetes. The defects in LV systolic flow velocity, acceleration, and jerk associated with sedentary diabetes were restored toward control levels in the trained diabetic animals. This magnetic resonance imaging study confirms the prevailing evidence from earlier in vitro and in vivo invasive procedures that exercise training benefits cardiac function in this model of diabetic cardiomyopathy despite the extreme catabolic state of the animals.

Animals↗

PubMed2006

A mouse model of sensorimotor controlled cortical impact: characterization using longitudinal magnetic resonance imaging, behavioral assessments and histology.

The present study establishes a new mouse model for traumatic brain injury (TBI), using an electromechanically driven linear motor impactor device to deliver a lateral controlled cortical impact (CCI) injury to the sensorimotor cortex. Lesion cavity size was measured, and inter-animal consistency demonstrated, at 14 days post injury. Qualitative information regarding damage progression over time was obtained by scanning with high field magnetic resonance imaging (MRI) at five time points following injury. Functional impairment and recovery were measured with the Rotarod, gridwalk and cylinder tests, and lesion cavity volume was measured post mortem with thionin-stained tissue sections. The study establishes the reliability of a linear-motor based device for producing repeatable damage in a CCI model, demonstrates the power of longitudinal MRI in studying damage evolution, and confirms that a simple battery of functional tests record sensorimotor impairment and recovery.

Animals↗

PubMed2006

Electrical stimulation of cortex improves corticospinal tract tracing in rat spinal cord using manganese-enhanced MRI.

Following bilateral injection of manganese (Mn) into the rat's motor cortex, electrical stimulation of the cortex is shown to increase the transport, uptake and accumulation of Mn in the corticospinal tract (CST), as assessed by manganese-enhanced magnetic resonance imaging (MEI). T(1)-weighted gradient echo images were acquired in 3-D and displayed in different orientations to anatomically delineate the CST pathway from cortex to spinal cord (SC) at the thoracic level. T(1)-maps of the SC were produced from spin-echo based image data to demonstrate the distribution of the T(1) properties of the SC tissue and to quantitatively assess the T(1)-change occurring in the CST due to the presence of Mn therein. Implications for improving the tract tracing ability with the proposed in vivo approach and its application to spinal cord injury (SCI) research are discussed in terms of aiding future experimental investigations of neuroplasticity following an injury.

Animals↗

PubMed2006

Magnetic resonance microscopy of spinal cord injury in mouse using a miniaturized implantable RF coil.

A magnetic resonance neuroimaging method is described for high-resolution imaging of spinal cord injury in live mouse. The method is based on a specially designed radio frequency coil system formed by a combination of an implantable coil and an external volume coil. The implantable coil is a 5 mm x 10 mm rectangular design with a 9.1 pF capacitor and 22 gauge copper wire and optimal for surgical implantation over the cervical or thoracic spine. The external volume coil is a standard birdcage resonator. The coils are inductively overcoupled for imaging the spinal cord at 9.4 T magnetic field strength. The inductive overcoupling provides flexibility in tuning the resonant frequency and matching the impedance of the implanted coil remotely using the tuning and matching capabilities of the volume coil. After describing the implementation of the imaging setup, in vivo data are gathered to demonstrate the imaging performance of the coil system and the feasibility of performing MR microscopy on injured mouse spinal cord.

Animals↗

PubMed2006

Cardiac dysfunction in the diabetic rat: quantitative evaluation using high resolution magnetic resonance imaging.

BACKGROUND: Diabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy. METHODS: In this study, we used high field magnetic resonance imaging (MRI) to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched controls. RESULTS: Our analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively) compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats. CONCLUSION: Thus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes.

Animals↗

PubMed2006

Improvement in survival and muscle function in an mdx/utrn(-/-) double mutant mouse using a human retinal dystrophin transgene.

Duchenne muscular dystrophy is a progressive muscle disease characterized by increasing muscle weakness and death by the third decade. mdx mice exhibit the underlying muscle disease but appear physically normal with ordinary lifespans, possibly due to compensatory expression of utrophin. In contrast, double mutant mice (mdx/utrn(-/-)), deficient for both dystrophin and utrophin die by approximately 3 months and suffer from severe muscle weakness, growth retardation, and severe spinal curvature. The capacity of human retinal dystrophin (Dp260) to compensate for the missing 427 kDa muscle dystrophin was tested in mdx/utrn(-/-) mice. Functional outcomes were assessed by histology, EMG, MRI, mobility, weight and longevity. MCK-driven transgenic expression of Dp260 in mdx/utrn(-/-) mice converts their disease course from a severe, lethal muscular dystrophy to a viable, mild myopathic phenotype. This finding is relevant to the design of exon-skipping therapeutic strategies since Dp260 lacks dystrophin exons 1-29.

Age Factors↗

PubMed2006

Inductively-overcoupled coil design for high resolution magnetic resonance imaging.

BACKGROUND: Maintaining the quality of magnetic resonance images acquired with the current implantable coil technology is challenging in longitudinal studies. To overcome this challenge, the principle of 'inductive overcoupling' is introduced as a method to tune and match a dual coil system. This system consists of an imaging coil built with fixed electrical elements and a matching coil equipped with tuning and matching capabilities. Overcoupling here refers to the condition beyond which the peak of the current in the imaging coil splits. METHODS: The combined coils are coupled inductively to operate like a transformer. Each coil circuit is electrically represented by equivalent lumped-elements. A theoretical analysis is given to identify the frequency response characteristics of the currents in each coil. The predictions from this analysis are translated into experiments and applied to locally image rat spinal cord at 9.4 T using an implantable coil as the imaging coil and an external volume coil as the matching coil. RESULTS: The theoretical analysis indicated that strong coupling between the coils divides the resonance peaks on the response curves of the currents. Once these newly generated peaks were tuned and matched to the desired frequency and impedance of operation, in vivo images were acquired from the rat spinal cord at high quality and high resolution. CONCLUSION: After proper implementation, inductive overcoupling provides a unique opportunity for tuning and matching the coil system, and allows reliable and repeatable acquisitions of magnetic resonance data. This feature is likely to be useful in experimental studies, such as those aimed at longitudinally imaging the rat following spinal cord injury.

Algorithms↗

PubMed2005

Characterization of alterations in diabetic myocardial tissue using high resolution MRI.

Cardiovascular complications, including diabetic cardiomyopathy, are the major cause of fatalities in diabetes. Diabetic cardiomyopathy is expressed in part through fibrosis and left ventricular hypertrophy, increasing myocardial stiffness leading to heart failure. In order to search for curative interventions, precise evaluation of the diabetic heart pathology is extremely important. Magnetic resonance imaging (MRI) is ideally suited for the assessment of heart disorders due to its high resolution, three-dimensional properties and dimensional accuracy. In this study streptozotocin injected Sprague-Dawley rats were used as a model of type 1 diabetes to characterize abnormalities in the diabetic left ventricle (LV). High resolution MRI using a 9.4 T horizontal bore scanner was performed on control and 7 weeks diabetic rats. In the diabetic rats as compared to controls, we found increased LV wall volume to body weight ratio, suggestive of LV hypertrophy; increased LV wall mean pixel intensity, and decreased T2 relaxation time, both suggestive of changes in the diabetic tissue properties, perhaps due to presence of fibrosis which was detected through increase in the collagen fractional area. In addition, changes in the LV cavity area were observed and quantified in post-mortem diabetic hearts indicative of stiffer and less resilient LV myocardial tissue with diabetes. Together the data suggest that LV hypertrophy and fibrosis may be a major factor underlying structural and functional abnormalities in the diabetic heart, and MRI is a valuable tool to non-invasively monitor the pathological changes in diabetic cardiomyopathy.

Animals↗

PubMed2005

Manganese-enhanced MRI of rat spinal cord injury.

The potential of the manganese-enhanced MRI (MEI) technique in labeling the intact neuronal circuitry of rat spinal cord was examined. Experiments were conducted on normal and injured cords at 9.4-T magnetic field strength using an implantable rf coil. The contrast agent manganese (Mn) was locally delivered within the parenchyma at a dose of 25 mmol/L in 10 nL. The transport, uptake and accumulation of Mn in tissue were then followed remotely on T1-weighted images that were acquired serially from the cord. In MEIs of normal cord, Mn was observed to be transported in directions both rostral and caudal to the site of injection. In the cord that was subjected to hemisection, signal enhancement was on the contralesional side of the cord, but not at the ipsilesional side. The sensitivity and specificity of the MEI technique in labeling the neurons that are functional were also validated with a traditional track-tracing method using biotinylated dextran amine.

Animals↗

PubMed2005

Microneurography of human median nerve.

PURPOSE: To examine the possibility of performing high-resolution MRI (microneurography) on peripheral nerves. MATERIALS AND METHODS: A specific radio frequency (RF) coil was developed to probe the human median nerve at a magnetic field strength of 9.4 T and tested on three excised samples by acquiring microneurograms. RESULTS: The microneurograms revealed neuronal tissue constituents at subfascicular level. The contrast features on proton-density and T1- and T2-weighted images were described and compared. The microscopic water movement was quantified using diffusion weighting parallel and orthogonal to the neuronal fiber orientation. The characteristics of anisotropic diffusion in the median nerve were comparable to those reported from other biological tissues (white matter and kidney). CONCLUSION: The results overall suggest that microneurography might provide new noninvasive insights into microscopic gross anatomy of the peripheral nerve, injury evaluation, and efficacy of repair, although the feasibility at current clinically relevant field strengths is yet to be determined.

Cadaver↗

PubMed2005

Magnetic resonance angiography of rat spinal cord at 9.4 T: a feasibility study.

In this study we investigated the feasibility of performing 3D time-of-flight magnetic resonance angiography to remotely image the arteries of rat spinal cord. Using a custom-designed implantable radiofrequency coil, we acquired angiograms from normal and injured cords. The potential of the approach was evaluated in terms of longitudinally monitoring the vascular reorganization of spinal cord following an injury.

Animals↗

PubMed2005

Magnetic resonance imaging of mouse spinal cord.

The feasibility of performing high-resolution in vivo MRI on mouse spinal cord (SC) at 9.4 T magnetic field strength is demonstrated. The MR properties of the cord tissue were measured and the characteristics of water diffusion in the SC were quantified. The data indicate that the differences in the proton density (PD) and transverse relaxation time between gray matter (GM) and white matter (WM) dominate the contrast seen on the mouse SC images at 9.4 T. However, on heavily T(2)-weighted images these differences result in a reversal of contrast. The diffusion of water in the cord is anisotropic, but the WM exhibits greater anisotropy and principal diffusivity than the GM. The quantitative data presented here should establish a standard for comparing similar measurements obtained from the SCs of genetically engineered mouse or mouse models of SC injury (SCI).

Algorithms↗

PubMed2005

Exact tandem repeats analyzer (E-TRA): a new program for DNA sequence mining.

Exact Tandem Repeats Analyzer 1.0 (E-TRA) combines sequence motif searches with keywords such as 'organs', 'tissues', 'cell lines' and 'development stages' for finding simple exact tandem repeats as well as non-simple repeats. E-TRA has several advanced repeat search parameters/options compared to other repeat finder programs as it not only accepts GenBank, FASTA and expressed sequence tags (EST) sequence files, but also does analysis of multiple files with multiple sequences. The minimum and maximum tandem repeat motif lengths that E-TRA finds vary from one to one thousand. Advanced user defined parameters/options let the researchers use different minimum motif repeats search criteria for varying motif lengths simultaneously. One of the most interesting features of genomes is the presence of relatively short tandem repeats (TRs). These repeated DNA sequences are found in both prokaryotes and eukaryotes, distributed almost at random throughout the genome. Some of the tandem repeats play important roles in the regulation of gene expression whereas others do not have any known biological function as yet. Nevertheless, they have proven to be very beneficial in DNA profiling and genetic linkage analysis studies. To demonstrate the use of E-TRA, we used 5,465,605 human EST sequences derived from 18,814,550 GenBank EST sequences. Our results indicated that 12.44% (679,800) of the human EST sequences contained simple and non-simple repeat string patterns varying from one to 126 nucleotides in length. The results also revealed that human organs, tissues, cell lines and different developmental stages differed in number of repeats as well as repeat composition, indicating that the distribution of expressed tandem repeats among tissues or organs are not random, thus differing from the un-transcribed repeats found in genomes.

Cells, Cultured↗

PubMed2005

Ex vivo magnetic resonance imaging of rat spinal cord at 9.4 T.

The magnetic resonance (MR) properties of the rat spinal cord were characterized at the T9 level with ex vivo experiments performed at 9.4 T. The inherent endogenous contrast parameters, proton density (PD), longitudinal and transverse relaxation times T1 and T2, and magnetization transfer ratio (MTR) were measured separately for the grey matter (GM) and white matter (WM). Analysis of the measurements indicated that these tissues have statistically different proton densities with means PD(GM)=54.8+/-2.5% versus PD(WM)=45.2+/-2.4%, and different T1 values with means T1GM=2.28+/-0.23 s versus T1WM=1.97+/-0.21 s. The corresponding values for T2 were T2GM=31.8+/-4.9 ms versus T2WM=29.5+/-4.9 ms, and the difference was insignificant. The difference between MTR(GM)=31.2+/-6.1% and MTR(WM)=33.1+/-5.9% was also insignificant. These results collectively suggest that PD and T1 are the two most important parameters that determine the observed contrast on spinal cord images acquired at 9.4 T. Therefore, in MR imaging studies of spinal cord at this field strength, these parameters need to be considered not only in optimizing the protocols but also in signal enhancement strategies involving exogenous contrast agents.

Animals↗

PubMed2005

A new device for experimental modeling of central nervous system injuries.

This article introduces a new device for inducing central nerve system injuries in experimental studies with animal models. The construction of the device is based on a commercially available servo-drive system incorporating the latest instrumentation technology and software developed in house to control the motion profile of the injury bit. The software, which is available upon request from the author, was designed such that the user can set the mechanical properties of the motion. For the purpose of quality control, tests were described and performed to assess the ability of the device to reproduce the prescribed motion when operated repetitively under the same set of parameters. Experiments were then conducted on animals to injure mouse brain and rat spinal cord. Following the injuries, in vivo magnetic resonance imaging was performed on the animals to depict the pathologies of the resulting injuries in the corresponding neuronal tissues. Rat spinal cords injured mildly and severely were followed longitudinally for up to 28 days postinjury. The neurobehaviors of the animals evaluated using locomotor rating scores indicated the ability of the device to produce repeatable graded injuries.

Animals↗

PubMed2004

A software program combining sequence motif searches with keywords for finding repeats containing DNA sequences.

MOTIVATION: One of the most interesting features of genomes (both coding and non-coding regions) is the presence of relatively short tandemly repeated DNA sequences known as tandem repeats (TRs). We developed a new PC-based stand-alone software analysis program, combining sequence motif searches with keywords such as organs, tissues, cell lines or development stages for finding exact, inexact and compound, TRs. Tandem Repeats Analyzer 1.5 (TRA) has several advanced repeat search parameters/options over other repeat finder programs as it does not only accept GenBank, FASTA and expressed sequence tag (EST) sequence files but also does analysis of multifiles with multisequences. Advanced user-defined parameters/options let the researchers use different motif lengths search criteria for varying motif lengths simultaneously. The outputs show statistical results to be evaluated by the user. The discovery of TRs in ESTs could be useful for both gene mapping and association studies and discovering TRs located in coding regions of important genes that are expressed under various conditions of environment, stress, organ, tissue and development stage. RESULTS: In this paper, we demonstrated applications of TRA using 175 899 ESTs sequences for three Arabidopsis spp. downloaded from GenBank. The EST-SSRs/ESTs ratios were found 43.1%, 15.3% and 2.34% in A.lyrata, A.thaliana and A.halleri, respectively. Analysis revealed that organs, tissues and development stages possessed different amounts of repeats and repeat compositions. This indicated that the distribution of TRs among the tissues or organs may not be random differing from the untranscribed repeats found in genomes. AVAILABILITY: The program can be obtained free by anonymous FTP from ftp.akdeniz.edu.tr/Araclar/TRA.

Arabidopsis↗