Biomedical subjects

O Nalcioglu

Publications and source records attributed to O Nalcioglu.

At least 19 recordsLinked to original sources

PubMed2003

Comparison of water and lipid content measurements using diffuse optical spectroscopy and MRI in emulsion phantoms.

We present a quantitative comparison of lipid and water signals obtained from broadband Diffuse Optical Spectroscopy (DOS) and Magnetic Resonance Imaging (MRI). DOS and MRI measurements were performed on an identical set of emulsion phantoms that were composed of different water/soybean oil fractions. Absolute concentrations of water and lipid ranging from 35-94% and 63-6%, respectively were calculated from quantitative broadband near-infrared (NIR) absorption spectra (650-1000 nm). MR images of fat and water were separated using the three-point Dixon technique. DOS and MRI measured water and lipid were highly correlated (R(2) = 0.98 and R(2) = 0.99, respectively) suggesting that these techniques are complementary over a broad range of physiologically relevant water and lipid values. In addition, comparison of DOS derived concentrations to the MRI "gold standard" technique validates our quantitation approach and permits estimation of DOS accuracy and sensitivity in vivo.

Emulsions↗

PubMed2002

Applications of dynamic contrast enhanced MRI in oncology: measurement of tumor oxygen tension.

A new model based on an extension of the Krog's cylindrical model was developed to calculate tumor oxygen tension (pO(2)) from the H-1 dynamic contrast enhanced MRI (DCE-MRI) measurements. The model enables one to calculate the tumor pO(2) using the vascular volume fraction (f(b)) obtained by the DCE-MRI. The proposed model has three parameters. For small values of f(b) one assumes that there exists a linear relationship between and f(b). The constant of proportionality in this case is given by C(1) - the oxygen tension per vascular volume fraction. For larger values of f(b) a modified version of Krogh model using two parameters is developed and here C(2) - is the integrated blood oxygen tension, and C(3) - given by the combination of the oxygen diffusion coefficient, solubility of oxygen in the tissue, capillary radius, and tissue metabolic consumption rate. The parameters of the model can be determined by performing simultaneous in-vivo F-19 MRI oxygen tension measurement and dynamic Gd-DTPA enhanced MRI on the same tumor. Dynamic MRI data can be used with a compartmental model to calculate tumor vascular volume fraction on a pixel by pixel basis. Then tumor oxygen tension map can be calculated from the vascular volume fraction by the extended Krogh model as described above. In the present work, the model parameters were determined using three rats bearing Walker-256 tumors and performing simultaneous F-19 and DCE MRI on the same tumor. The parameters obtained by fitting the model equation to the experimental data were: C(1) = 983.2 +/- 133.2torr, C(2) = 58.20 +/- 2.4 torr, and C(3) = 1.7 +/- 0.1 torr. The performance of the extended Krogh model was then tested on two additional rats by performing both F-19 and DCE-MRI studies and calculating the pO(2) (H-1) using the model and comparing it with the pO(2) (F-19) obtained from the F-19 MRI. It was found that the measurements obtained by both techniques had a high degree of correlation [pO(2) (H-1) = (1.01 +/- 0.07) pO(2) (F-19) + (0.91 +/- 0.05) and r=0.96], indicating the applicability of the proposed model in determining pO(2) from the DCE-MRI.

Animals↗

PubMed2001

Selective thrombosis of tumor blood vessels in mammary adenocarcinoma implants in rats.

Adenocarcinomas in rats and humans frequently contain perivascular, degranulating mast cells that release heparin. Protamine is a low-molecular weight, cationic polypeptide that binds avidly to heparin and neutralizes its anticoagulant properties. We hypothesized that mast-cell heparin functions as a localized anticoagulant that modulates hemostasis and blood perfusion in tumors. Consequently, systemically administered protamine should be able to neutralize the endogenous heparin within tumors, thereby inducing selective thrombosis of blood vessels within tumors. Here we demonstrate with magnetic resonance imaging (MRI) that an intravenous dose of protamine labeled with gadolinium accumulated within the parenchyma of subcutaneous implants of a mammary adenocarcinoma in Fischer 344 rats. Moreover, we show with dynamic contrast enhanced MRI that sequential intravenous doses of protamine in 12 tumor-bearing rats resulted in significantly decreased signal enhancement kinetics (blood perfusion) of the tumor. This functional impairment of MRI signal enhancement was accompanied by histological evidence of thrombosis in the blood vessels within the tumor. There was no histological evidence of thrombosis within normal liver, kidney, lung, spleen, or adjacent muscle of tumor-bearing animals that received protamine treatment or in the tumors of animals that had not been pretreated with protamine. On the basis of these results, we conclude that protamine accumulates within adenocarcinoma implants and induces selective thrombosis of blood vessels within the tumor, probably by neutralizing the endogenous heparin within tumors.

Adenocarcinoma↗

PubMed2001

Effect of vasodilator hydralazine on tumor microvascular random flow and blood volume as measured by intravoxel incoherent motion (IVIM) weighted MRI in conjunction with Gd-DTPA-Albumin enhanced MRI.

We studied the effect of hydralazine on tumor blood volume fraction and microvascular random flow velocity magnitude by IVIM weighted MRI in conjunction with dynamic Gd-DTPA-Albumin enhanced MRI. Blood volume fraction maps were obtained from the dynamic Gd-DTPA-Albumin enhanced MRI measurements. The average blood volume fraction of R3230 AC adenocarcinoma decreased from 0.125 +/- 0.022 (s.d.) ml/g to 0.105 +/- 0.018 (s.d.) ml/g (p < 0.001) after the administration of hydralazine at a dose of 5 mg/kg. The microvascular random flow velocity magnitude maps were obtained from the IVIM weighted MRI signals by utilizing the Gd-DTPA-Albumin measured blood volume fractions as an input in the compartmental modeling analysis of the IVIM weighted MRI signal. The random-directional microvascular flow induced MRI signal attenuation was separated from the molecular diffusion induced signal attenuation. Flow induced attenuation was more significant after the administration of hydralazine. The mean microvascular random flow velocity magnitude increased from 0.52 +/- 0.15 (s.d.) mm/sec to 0.73 +/- 0.23 (s.d.) mm/sec (p < 0.05) in the presence of the above blood volume fraction change.

Adenocarcinoma↗

PubMed2001

FMRI study relevant to the Mozart effect: brain areas involved in spatial-temporal reasoning.

Behavioral studies, motivated by columnar cortical model predictions, have given evidence for music causally enhancing spatial-temporal reasoning. A wide range of behavioral experiments showed that listening to a Mozart Sonata (K.448) gave subsequent enhancements. An EEG coherence study gave evidence for a carryover from that Mozart Sonata listening condition to the subsequent spatial-temporal task in specific cortical regions. Here we present fMRI studies comparing cortical blood flow activation by the Mozart Sonata vs. other music. In addition to expected temporal cortex activation, we report dramatic statistically significant differences in activation by the Mozart Sonata (in comparison to Beethoven's Fur Elise and 1930s piano music) in dorsolateral pre-frontal cortex, occipital cortex and cerebellum, all expected to be important for spatial-temporal reasoning. It would be of great interest to explicitly test this expectation. We propose an fMRI study comparing (subject by subject) brain areas activated in music listening conditions and in spatial-temporal tasks.

Acoustic Stimulation↗

PubMed2000

Improvement of temporal resolution in fMRI using slice phase encode reordered 3D EPI.

A magnetic resonance imaging (MRI) pulse sequence was developed for acquiring high temporal resolution 3D functional magnetic resonance images (fMRI). The technique uses a 3D-acquisition scheme that increases the SNR per unit time. Compared to the previously developed methods, the proposed one does not sacrifice the spatial resolution or require a reduction in the number of acquired slices. The method was tested on six control subjects using a well-known visual activation task. Statistical analysis of the acquired data showed significant activation in the primary visual cortex of each subject. The proposed acquisition method makes use of the periodicity of the applied stimulus. A given kz plane is scanned sequentially using a modified 3D EPI pulse sequence while the stimulus cycle (SC) is applied. The same SC is repeated for each acquisition of a new kz plane sequence. After data acquisition, temporal reordering is done on the data to obtain the proper 3D image sequence. Since the familiarization of the subject with the activation task is an important aspect that might affect the performance of the method, habituation of the primary visual cortex was tested by applying a similar visual stimulus and acquiring data using standard 2D Echo Planar Imaging (EPI). No habituation was observed within a duration of 7 min 12 sec.

Adult↗

PubMed2000

Prediction of gene therapy-induced tumor size changes by the vascularity changes measured using dynamic contrast-enhanced MRI.

We studied the changes of tumor size after gene therapy treatment and its relationship with the changes of vascular volume as measured by dynamic contrast-enhanced magnetic resonance imaging (MRI), to investigate whether the vascular changes is predictive of tumor regression. The study was carried out using a spontaneously regressing rat tumor model (C6 Glioma grown subcutaneously in rats). Three rats were treated with recombinant adenoviruses expressing three genes, mouse interleukin 1-alpha (IL1-alpha), mouse interferon gamma (IFN-gamma), and human transforming growth factor beta (TGF-beta), one from each kind. Two rats were treated with saline as controls. Longitudinal studies were performed to monitor the changes of tumor volume (based on T(2)-weighted images) and the vascular volume (based on dynamic contrast enhanced images). In untreated animals, tumor regression was preceded by several days with a decrease in vascular volume. When the tumor growth was perturbed by expression of mouse IL-1alpha, the increase in vascular volume was correlated with the continuing growth in size, and the decrease in vascular volume was predictive of the onset of tumor regression. As new advances in immunotherapy in cancer treatment emerge, the ability to determine the efficacy of therapy as early as possible will enable optimization of treatment regiments. The vascularity changes measured by dynamic MRI may provide a means to serve for this purpose.

Adenoviridae↗

PubMed1999

Investigation of longitudinal vascular changes in control and chemotherapy-treated tumors to serve as therapeutic efficacy predictors.

The impact of chemotherapy on longitudinal vascular changes taking place during the growth of an animal tumor, R3230 AC adenocarcinoma, was investigated. Two contrast agents of different molecular weights, gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA; < 1 kD) and gadomer-17 (35 kD), were used in the dynamic imaging studies. Enhancement kinetics were analyzed by a pharmacokinetic model to derive parameters related to vascular volume and permeability on a pixel-by-pixel basis. Responders and non-responders were separated according to tumor size 10 days after the therapy. Changes in the vascular volume measured by gadomer-17 at 4 days after therapy revealed a clear distinction between the controls and the responders/non-responders. Mean vascular volume decreased by 42% in responders but was not significantly changed in the controls. The one non-responder had increased vascular volume after chemotherapy. Enhancement kinetics of gadomer-17 detected the changes earlier and with greater sensitivity than Gd-DTPA. In the control group, vascular permeability determined by gadomer-17 correlated with the longitudinal growth rates of tumors, suggesting that vascular permeability assessed by gadomer-17 could potentially serve as an indicator of aggressive tumor growth.

Adenocarcinoma↗

PubMed1999

Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents.

A carcinogen (N-ethyl-N-nitrosourea)-induced animal tumor model was established to grow malignant and benign breast tumors. In each tumor the pharmacokinetic characteristics were measured by using three contrast agents, gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA; <1 kD), Gadomer-17 (35 kD), and albumin-Gd-DTPA (70-90 kD). Infiltrating ductal carcinomas (IDC) with low, medium, and high Scarf-Bloom-Richardson grades and fibroadenomas (FA) were analyzed. We found that Gd-DTPA could differentiate between FA and malignant tumors, but not between malignant tumors of low and high grades. In contrast, the intermediate size agent Gadomer-17 could differentiate between high-grade and low-grade IDC, but not between low-grade IDC and FA due to their similar enhancement patterns (despite their different origins). The largest agent, albumin-Gd-DTPA, was capable of differentiating both, but the low contrast-to-noise ratio was its major technical concern. The results in this breast tumor model suggest that macromolecular agents provide useful information for differential diagnosis among IDCs of various grades, but they do not provide superior information than Gd-DTPA for differential diagnosis between IDC and FA.

Albumins↗

PubMed1998

Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights.

Dynamic contrast-enhanced MR imaging was used to measure the kinetics of enhancement in three different animal tumor models (Walker 256, R3230 AC, MCF7) using three different Gd complexes (Gd-DTPA, Gd-DTPA-24-cascade-polymer 30 kD, and polylysine-Gd-DTPA 50 kD). The three tumor models varied in growth rate, with the most rapid growth demonstrated by Walker 256 cells and the slowest growth occurring in the MCF7 cells. For each tumor, the kinetics of enhancement using polylysine-Gd-DTPA was analyzed using a pharmacokinetic model to estimate the vascular volume of the tumor. The rate of entry of the contrast agent into the interstitial space served as the measure of vascular permeability. The smallest molecular-weight agent, Gd-DTPA, could not provide information about vascular permeability. The intermediate and the largest agents both demonstrated that the faster-growing Walker 256 tumor had greater vascular permeability than did the slower-growing R3230 AC tumor. The degree of vascular permeability in the MCF7 tumor could not be assessed fairly due to insufficient statistics. The current study provides evidence supporting the hypothesis that more rapidly growing tumors have higher vascular permeability than do tumors that grow more slowly.

Animals↗

PubMed1998

Measurement of tumor vascular volume and mean microvascular random flow velocity magnitude by dynamic Gd-DTPA-albumin enhanced and diffusion-weighted MRI.

Tumor vascular volume fraction and the magnitude of the mean microvascular random flow velocity were measured in an animal tumor model by combining dynamic Gd-DTPA-albumin enhanced MRI and diffusion-weighted MRI in conjunction with a compartmental modeling analysis. The vascular volume fraction maps were obtained from the dynamic Gd-DTPA-albumin enhanced MRI measurement. It was found that the vascular volume fraction for Walker 256 tumor was higher within the outgrowing rim and decreased towards the central region. The average value obtained from five animals was 0.062 +/- 0.009 ml/g. By using the vascular volume fraction from the Gd-DTPA-albumin enhanced MRI measurement, maps of the magnitude of the mean microvascular random flow velocity were obtained from the diffusion-weighted MRI measurements with the compartmental modeling analysis. The relative extravascular and intravascular contributions to the diffusion-weighted MRI signal were determined for three tissue groups with different Gd-DTPA-albumin enhancement characteristics, and the flow and molecular diffusion-induced attenuation factors for the intravascular compartment were also compared. The mean microvascular random flow velocity magnitude maps were obtained with an average value of 0.67 +/- 0.06 mm/s.

Albumins↗

PubMed1997

An FEM approach for the characterization of the RF field homogeneity at high field.

High field magnetic resonance offers new opportunities because of its high SNR and better spectral resolution for MRI and MRS. However, new problems also emerge at high field. As the field strength increases, the wavelength in the tissue becomes shorter and comparable with the body dimensions. This perturbs the field and also causes standing waves within the patient as a result of the impedance mismatching at the tissue interfaces. Due to the complexity of the boundary conditions and the solution of Maxwell's equations, an exact analytical calculation for a loaded RF resonator has not been possible. In this paper, we present a birdcage coil simulation study based on a 3D finite element method (FEM) model for the characterization of the field within the tissue. First, the accuracy of the FEM solutions is validated by the 2D analytical solutions at 64 and 223 MHz. In these solutions, the frequency dependence of the conductivity and permittivity is also taken into account. Then, a more realistic 3D model is studied. The results are compared with the experimental measurements. It is shown that the 3D model makes it possible to explore the effects of the end rings in the presence of a tissue sample inside the coil.

Humans↗

PubMed1996

Pharmacokinetic changes induced by vasomodulators in kidneys, livers, muscles, and implanted tumors in rats as measured by dynamic Gd-DTPA-enhanced MRI.

The effects of three physiologically different vasomodulators, angiotensin II (a vasoconstrictor), hydralazine (a vasodilator), and histamine (a permeability modulator), on the pharmaco-kinetics of entry of small molecules (measured by Gd-DTPA concentration) into normal and abnormal tissue were studied in rats implanted with R3230 AC tumors. Sequential dynamic Gd-DTPA-enhanced MRI studies, one before and one after vasomodulator administration, were performed, and the signal intensities of various tissues analyzed. Angiotensin II (6 micrograms/kg) reduced blood flow in tumors, but increased it in muscles. Hydralazine (5 mg/kg) reduced blood flow in tumors, kidneys, and livers, and slowed Gd-DTPA clearance from tumors, livers, and muscles. Histamine (25 micrograms/kg) increased renal blood flow, hastening Gd-DTPA clearance causing reduced measurable blood flow in tumors and muscles. By simultaneously monitoring the effects in various tissues, the pharmacokinetic effect of each drug in the entire body could be obtained.

Adenocarcinoma↗

PubMed1995

Homonuclear J-refocused spectral editing technique for quantification of glutamine and glutamate by 1H NMR spectroscopy.

Quantification of the excitatory amino acid of glutamine and glutamate is extremely important partly because, when in excessive amounts, they can produce neuronal damage. However, quantification of such metabolites seems to be not straightforward owing to a large number of metabolic signals, particularly between the 2.0- and 3.0-ppm chemical shift range. The authors investigated a quantification method by using a homonuclear J-refocused spectral editing technique, namely the J-refocused PRESS (JPRESS), using both 1.5- and 4-T whole body NMR systems. At first, the J-coupling modulation of each metabolite at different TE values using the PRESS and JPRESS pulse sequences was compared. The suppression of J modulations with the JPRESS is well demonstrated on condition that TE values are less than 1/4J. Then, the accuracy of glutamate quantification after subtracting the two spectra obtained at two different echo times and integrating the difference spectral area at different concentrations was evaluated. The results exhibit an excellent linear relationship between the actual concentration versus the difference spectral peak area at both 1.5 and 4 T. The achievable minimum voxel size was also considered and a 1-ml voxel size seems to be possible at the typical glutamate concentration in vivo at a field strength of 4 T.

Algorithms↗

PubMed1995

Regional comparison of tumor vascularity and permeability parameters measured by albumin-Gd-DTPA and Gd-DTPA.

Sequential albumin-Gd-DTPA and Gd-DTPA dynamic enhancement studies were performed in an animal tumor model for the comparison of regional vascularity and permeability parameters measured by these two different sizes of contrast agents. The early albumin-Gd-DTPA enhancement arises from the vascular compartment, and the averaged signal enhancement derived from the first 3 to first 6 images postinjection can be reliably used to assess vascularity. The signal intensity in the images during the period of 5-10 min post-albumin-Gd-DTPA injection shows a steady linear variation. The intercept of the linear relationship is another indicator of the vascularity and the slope represents the tumor permeability to albumin-Gd-DTPA. The Gd-DTPA enhancement study was analyzed by a two-compartmental pharmacokinetic model to calculate the regional vascularity and permeability. The permeability parameters measured from albumin-Gd-DTPA and Gd-DTPA show an excellent correlation. The vascularity parameters measured from albumin-Gd-DTPA show good linear correlation with the low vascularity groups measured by Gd-DTPA, but show saturation for the high vascularity groups. The enhancement mechanisms for both contrast agents are discussed to relate the imaging parameters to the physiological variables.

Albumins↗

PubMed1995

Data analysis for dynamic contrast-enhanced MRI-based cerebral perfusion measurements: correcting for changing cortical CSF volumes.

The time evolution of the histogram (number of pixels versus signal intensity) is used to calculate delta R2 parameters from dynamic contrast-enhanced magnetic resonance (MR) imaging of the brain. This method partially corrects for partial volume effects and is an improvement over the approach using the signal intensity as a function of time when confounding factors such as changing cortical cerebrospinal fluid volumes are involved. The maximum value for delta R2 is found to correlate with relative cerebral blood flow as assessed by xenon inhalation and can be used to discriminate between vascular dementia and healthy volunteers. With this method, the normal range for delta R2 values is found to be the same for both young (19-40 years old) and elderly (65-85 years old) healthy volunteers.

Adult↗

PubMed1994

Cortical CSF volume fluctuations by MRI in brain aging, dementia and hydrocephalus.

Dynamic MR imaging has revealed dramatic fluctuations in the appearance of CSF in the cortical sulci and cortical subarachnoid spaces in aging individuals and patients with hydrocephalus, dementia and Down syndrome in contrast to young healthy volunteers. The changes have been interpreted as volume fluctuations that represent undamped CSF hydrodynamics and have implications with respect to the origin of CSF in the cortical regions and with respect to the similarity between aging and dementia and edematous states of the brain.

Adult↗

PubMed1994

Measurement of vascular volume fraction and blood-tissue permeability constants with a pharmacokinetic model: studies in rat muscle tumors with dynamic Gd-DTPA enhanced MRI.

We propose a compartmental model to explain the signal enhancement curves following the bolus injection of Gd-DTPA. The model incorporates vascular volume fraction contribution, and the possibility of having different transport constants between the plasma and extravascular components. A Walker 256 carcinoma grown in rat muscle was used to demonstrate the capability of this model. Several different types of tissues were included in the measurements: normal, quickly enhanced, slowly enhanced, and necrotic tissues. Blood volume and blood-tissue permeability information can be derived from the dynamic contrast-enhanced MRI study employing the proposed model. In the tissue contrast enhancement curve, the initial rising slope after injection is related to the blood volume (or, vascular volume fraction), the maximum enhancement ratio is related to the uptake of tissue, and the decay rate is related to the clearance of tracer from tissue. The measured permeability constant is not the conventional permeability; instead they are contrast agents uptake and clearance rates, which are limited by the blood perfusion. These parameters can be used to characterize different enhancement patterns.

Albumins↗