Biomedical subjects

Orhan Nalcioglu

Publications and source records attributed to Orhan Nalcioglu.

At least 19 recordsLinked to original sources

PubMed2006

An inverse method to design RF coil arrays optimized for SENSE imaging.

A new method to design MRI RF coils that are optimized for SENSE (sensitivity encoding) imaging is introduced. In this approach, the inverse problem was solved where the surface current density distribution on a coil former was calculated to maximize the SNR(sense) within a volume of interest (VOI). For that purpose, an analytic relationship was formulated between the SNR(sense) and surface current density on the coil former. The SNR at pixel rho in a SENSE-MR image, SNR(sense,rho), is inversely proportional to the g-factor: therefore, the g-factor was formulated in terms of the B1 distribution of the coils. Then, by specifying the geometry of the desired coil former and using a finite element mesh (FEM), the surface current distribution was calculated to maximize the SNR(sense), by minimizing (1/SNR(sense)) in the VOI using a least squares procedure. A simple two-coil array was designed and built to test the method and phantom images were collected. The results show that the new coil design method yielded better uniformity and SNR in SENSE images compared to those of standard coils.

Algorithms↗

PubMed2006

Contrast and spatial resolution in MREIT using low amplitude current.

Magnetic resonance-electrical impedance tomography employs low amplitude currents injected or induced inside an object. The additional magnetic field due to these currents results in a phase in the MR images. In this study, a modified fast spin-echo sequence was used to measure this magnetic field, which is obtained by scaling the MR phase image. A finite element method with first order triangular elements was used for the solution of the forward problem. An iterated sensitivity matrix-based algorithm was developed for the inverse problem. The resulting ill-conditioned matrix equation was regularized using the Tikhonov method and solved using a conjugate gradient solver. The spatial and contrast resolution of the technique was tested using agarose gel phantoms. A circular phantom with 7 cm diameter and 1 cm thickness is used in the phantom experiments. The amplitude of the injected current was 1 mA. 3, 5 and 8 mm diameter insulators and high conductor objects are used for the spatial resolution study and an average full-width half-maximum value of 4.7 mm is achieved for the 3 mm insulator case. For the contrast analysis, the conductivity of a 15 mm object is varied between 44% and 500% with respect to the background and results are compared to the ideal reconstruction.

Algorithms↗

PubMed2006

Quantification of choline-containing compounds in malignant breast tumors by 1H MR spectroscopy using water as an internal reference at 1.5 T.

The quantification of choline-containing compounds (Cho) in breast tumors by proton MR spectroscopy (1H-MRS) has been of great interest because such compounds have been linked to malignancy. In this study, an internal reference method for the absolute quantification of Cho metabolite in malignant breast tumors was presented using a clinical 1.5 T scanner. We performed in vitro measurements to examine the accuracy of absolute quantification using four phantoms of known choline chloride concentrations. There was a high correlation between the calculated concentrations by MRS and the known concentrations (r2 > 0.98). We applied the technique to in vivo breast study conducted on 45 patients with biopsy-confirmed breast cancer. After T1 and T2 relaxation times were corrected, the Cho levels in this work had a range of 0.76-21.20 mmol/kg from 34 MR spectra of 32 patients with malignant breast lesions. This result was rather consistent with the previously published value (i.e., 1.38-10 mmol/kg, Bolan et al. in Magn Reson Med 50:1134-1143, 2003). Therefore, we conclude that the internal method using the fully relaxed water as a reference could be used for quantifying Cho metabolite accurately in breast cancer patients using a clinical 1.5 T scanner.

Breast Neoplasms↗

PubMed2006

Measurement of ion diffusion using magnetic resonance electrical impedance tomography.

In magnetic resonance electrical impedance tomography (MREIT), currents are applied to an object, the resulting magnetic flux density measured using MRI and the conductivity distribution reconstructed using these MRI data. In this study, we assess the ability of MREIT to monitor changes in the conductivity distribution of an agarose gel phantom, using injected current pulses of 900 microA. The phantom initially contained a distinct region of high sodium chloride concentration which diffused into the background over time. MREIT data were collected over a 12 h span, and conductivity images were reconstructed using the iterative sensitivity matrix method with Tikhonov regularization. The results indicate that MREIT was able to monitor the changing conductivity and concentration distributions resulting from the diffusion of ions within the agarose gel phantom.

Algorithms↗

PubMed2006

Resolution improvement in positron emission tomography using anatomical Magnetic Resonance Imaging.

An ideal imaging system should provide information with high-sensitivity, high spatial, and temporal resolution. Unfortunately, it is not possible to satisfy all of these desired features in a single modality. In this paper, we discuss methods to improve the spatial resolution in positron emission imaging (PET) using a priori information from Magnetic Resonance Imaging (MRI). Our approach uses an image restoration algorithm based on the maximization of mutual information (MMI), which has found significant success for optimizing multimodal image registration. The MMI criterion is used to estimate the parameters in the Sharpness-Constrained Wiener filter. The generated filter is then applied to restore PET images of a realistic digital brain phantom. The resulting restored images show improved resolution and better signal-to-noise ratio compared to the interpolated PET images. We conclude that a Sharpness-Constrained Wiener filter having parameters optimized from a MMI criterion may be useful for restoring spatial resolution in PET based on a priori information from correlated MRI.

Algorithms↗

PubMed2006

Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals.

Recently, there has been a great amount of interest in developing multi-modality imaging techniques for oncologic research and clinical studies with the aim of obtaining complementary information and, thus, improving the detection and characterization of tumors. In this present work, the details of a combined MR-diffuse optical imaging system for dual-modality imaging of small animals are given. As a part of this effort, a multi-spectral frequency domain diffuse optical tomography system is integrated with an MRI system. Here, a network analyzer provides the rf modulation signal for the laser diodes and measures the amplitude and the phase of the detected signals. Photomultiplier tubes are utilized to measure low-level signals. The integration of this optical imaging system with the 4T MRI system is realized by incorporating a fiber adaptive interface inside the MR magnet. Coregistration is achieved by a special probe design utilizing fiducial markers. A finite element algorithm is used to solve the diffusion equation and an inverse solver based on this forward solver is implemented to calculate the absorption and scattering maps from the acquired data. The MR a priori information is used to guide the optical reconstruction algorithm. Phantom studies show that the absorption coefficient of a 7 mm inclusion in an irregular object located in 64 mm phantom is recovered with 11% error when MR a priori information is used. ENU induced tumor model is used to test the performance of the system in vivo.

Algorithms↗

PubMed2006

In vivo MRI electrical impedance tomography (MREIT) of tumors.

A significant increase in electrical conductivity of neoplasticities compared to healthy tissues and benign formations has been reported in several studies. We previously reported preliminary results with MR based Electrical Impedance Tomography (MREIT) on several phantoms and a single animal. In the presented study, we applied the technique on ten tumor-bearing rats and collected MREIT images to investigate the potential of MREIT for characterizing malignant tumors. Results show that the tumors had significantly higher mean conductivity compared to the mean of conductivity in the rest of the body. Although heterogeneity of conductivity was observed in the tumor, the mean was still higher than the background.

Algorithms↗

PubMed2006

Comparison of choline and pharmacokinetic parameters in breast cancer measured by MR spectroscopic imaging and dynamic contrast enhanced MRI.

Although an MRI scanner is a single stand-alone modality, different acquisition techniques may be applied to collect structural and functional information, including vascular or angiogenic properties measured by dynamic contrast enhanced MRI (DCE-MRI) and Choline (Cho) metabolism measured by proton MR spectroscopy imaging (MRSI). They may provide complementary information for a better characterization of neoplasm. In this study, we investigated the correlation between Choline measured by MRSI and vascular parameters measured by DCE-MRI in breast cancer. Fourteen patients with histologically proven invasive breast cancer were included. MRSI from a grid of 8 x 8 voxels within a selected slab from each lesion was performed. Each voxel was 1.0 x 1.0 x 1.2 cm3. Choline signal-to-noise ratio (SNR) was measured from each voxel showing an identifiable Choline peak. Corresponding DCE kinetics was measured from each voxel, and analyzed with a 2-compartmental model to obtain pharmacokinetic parameters Ktrans and k(ep). All parameters showed a wide variation within each lesion, and there were no consistent correlations between regional Cho and DCE parameters within the lesion of each individual patient. This finding might be attributed to the heterogeneous nature of breast cancer. The characteristic Cho and DCE-MRI parameters were obtained for each patient by averaging over all Cho-positive voxels. In these 14 patients there was a significant linear correlation between Cho with percent enhancement at 2 min after injection, SE%-2min (r = 0.75, p = 0.002), and pharmacokinetic parameters Ktrans (r = 0.74, p = 0.003), and k(ep) (r = 0.76, p = 0.002). The results suggested that overall there is a correlation between Choline metabolism and angiogenesis activity. Since Choline is associated with cell replication and angiogenesis is required to support tumor growth, this might explain the correlation between these two sets of measures among different lesions.

Adult↗

PubMed2005

Pharmacokinetic parameters analyzed from mr contrast enhancement kinetics of multiple malignant and benign breast lesions detected in the same patients.

Ninety-nine patients with confirmed breast cancer were reviewed to identify patients who had two confirmed malignant lesions of identical pathology (Group-1, N = 17), and patients who had one malignant lesion and the second benign lesion (Group-2, N = 8). Contrast enhancement kinetics from every lesion was measured and analyzed using three different models to obtain fitting parameters related to up-slope, enhancement amplitude, and wash-out, including Model-1: modified Tofts model (v(p), Ktrans, k(ep)), Model-2: standard Tofts model (Ktrans, k(ep)), and Model-3: a 3-parameter heuristic model (Tc, A, C). By analyzing lesions from same patients, the differences in whole body hemodynamics thus the blood kinetics could be controlled. Two questions were addressed in this study: i) What is the association between pharmacokinetic parameters analyzed from multiple cancers of identical pathology in same patients?; and ii) What is the difference between secondary malignant lesions and secondary benign lesions with reference to the primary cancer? All three models could fit the enhancement kinetics satisfactorily. Regardless of the analysis model the parameter obtained from the primary cancer and the secondary cancer showed significant correlations. In comparison between Group-1 and Group-2 subjects, the wash-out parameter kep in Models-1 and 2 could significantly differentiate benign from malignant lesions, but not the magnitude parameters, Ktrans in Model-2 or the parameter A in Model-3. If analyzed using appropriate models the early up-slope parameters, v(p) in Model-1 and Tc in Model-3, might be able to distinguish between benign and malignant lesions. When more data are available a reference database can be established with the method described in this study, and from which to determine the likelihood of malignancy for each incidental lesion found in preoperative MRI, with reference to the primary cancer.

Breast Diseases↗

PubMed2005

Coregistration of dynamic contrast enhanced MRI and broadband diffuse optical spectroscopy for characterizing breast cancer.

A hand-held scanning probe based on broadband Diffuse Optical Spectroscopy (DOS) was used in combination with dynamic contrast enhanced MRI (DCE-MRI) to quantitatively characterize locally-advanced breast cancers in six patients. Measurements were performed sequentially using external fiducial markers for co-registration. Tumor patterns were categorized according to MRI morphological data, and 3D DCE-MRI slices were converted into a volumetric matrix with isotropic voxels to generate views that coincided with the DOS scanning plane. Tumor volume and depth at each DOS measurement site were determined, and a tissue optical index (TOI) that reflects both angiogenic and stromal characteristics was derived from broadband DOS data. In all six cases, optical scans showed significant TOI contrast corresponding to MRI morphological information. Sharp TOI peaks were recovered for well-circumscribed masses. A reduction in TOI was found inside a tumor with a necrotic center. A broadened peak was observed for a diffuse tumor pattern, and an inflammatory septal case provided two TOI peaks that correlated qualitatively with MRI enhancement. These results provide qualitative confirmation of the common signal origin and complementary information content that can be achieved by combining optical and MR imaging for breast cancer detection and clinical management.

Adult↗

PubMed2004

Serial MRI after experimental febrile seizures: altered T2 signal without neuronal death.

Whereas most febrile seizures (FSs) carry a benign outcome, a subpopulation of individuals with prolonged FSs are at risk for later temporal lobe epilepsy. Signal changes on magnetic resonance imaging (MRI) may provide early markers for changes in neuronal integrity that may promote epileptogenesis in such individuals. Here, we used serial MRIs, obtained before and at several time points after experimental prolonged FSs, to determine the prevalence and distribution of signal changes on T2-weighted images and to investigate the pathological substrates leading to these changes. Seventy-five percent of immature rats with experimental prolonged FSs had abnormal T2 signal enhancement at 24 hours, and 87.5% at 8 days after the seizures. The altered T2 values involved the dorsal hippocampus (75%), the piriform cortex (87.5%), and the amygdala (25%). However, these changes were not accompanied by evidence of neuronal injury or death in these regions, as assessed using the Fluoro-Jade method. Thus, experimental prolonged FSs lead to relatively frequent abnormal MRI signal in "temporal lobe" structures. Although these changes do not signify cell death, they may denote pathological cellular processes that promote epileptogenesis. .

Animals↗

PubMed2004

Increased blood clotting, microvascular density, and inflammation in eotaxin-secreting tumors implanted into mice.

An important theme that is emerging in cancer research is the interaction between tumor cells and the host stroma. Because many types of human cancer are infiltrated by eosinophils that are believed to mediate an anti-tumor cytotoxic effect, we developed and studied a transfected B16 murine melanoma cell line that secretes high levels (510 pg/ml/100,000 cells/day) of eotaxin, a chemokine that recruits and activates primarily eosinophils. Here we report that there was increased inflammation (eosinophils, mast cells, mononuclear cells), blood clotting, and microvascular density within the tumors produced by subcutaneous implants of eotaxin-secreting tumor cells in 10 C57BL/6 compared to tumors produced by wild-type tumor cells. The extensive blood clotting in the eotaxin-transfected tumors was associated with significantly decreased blood flow to the tumors as measured by magnetic resonance imaging [(mean maximum signal enhancement of eotaxin-secreting tumors, 147 +/- 57 (n = 7) compared to 202 +/- 36 signal enhancement units (n = 8) for the wild-type melanoma cells; P = 0.04 by two-tailed, unpaired t-test]. Surprisingly, there was no significant difference between the growth rates or mean masses of the eotaxin-secreting tumors (750 +/- 280 mg, n = 10) and the wild-type tumors (780 +/- 290, n = 10) after 20 days of growth in vivo, despite the significantly slower growth rate in vitro of the eotaxin-secreting tumor cells. We conclude that eotaxin and the resultant tumor-infiltrating inflammatory cells are not likely to mediate a significant anti-tumor effect in vivo. Instead, elevated eotaxin is associated with increased inflammation, microvascular density, and blood clotting. Thus, eotaxin and eosinophils may play a more complex role in modulating the growth of tumors than the simple, anti-tumor cytotoxic effect that has been previously proposed.

Animals↗

PubMed2004

Resolution and contrast in magnetic resonance electrical impedance tomography (MREIT) and its application to cancer imaging.

It has been reported that the electrical impedance of malignancies could be 20-40 times lower than healthy tissues and benign formations. Therefore, in vivo impedance imaging of suspicious lesions may prove to be helpful in improving the sensitivity and specificity of detecting malignant tumors. Several systems have been developed to map the conductivity distribution inside a volume of tissue, however they suffer from poor spatial resolution because the measurements are taken only from surface electrodes. MRI based impedance imaging (MREIT) is a novel method, in which weak electrical currents are injected into the tissue and the resulting perturbations in the magnetic field are measured using MRI. This method has been shown to provide better resolution compared to previous techniques of impedance imaging because the measurements are taken from inside the object on a uniform grid. Thus, it has the potential to be a useful modality that may detect malignancies earlier. Several phantom imaging experiments were performed to investigate the spatial resolution and dynamic range of contrast of this technique. The method was also applied to a live rat bearing a R3230 AC tumor. Tumor location was identified by contrast enhanced imaging.

Animals↗

PubMed2003

In vivo quantification of optical contrast agent dynamics in rat tumors by use of diffuse optical spectroscopy with magnetic resonance imaging coregistration.

We present a study of the dynamics of optical contrast agents indocyanine green (ICG) and methylene blue (MB) in an adenocarcinoma rat tumor model. Measurements are conducted with a combined frequency-domain and steady-state optical technique that facilitates rapid measurement of tissue absorption in the 650-1000-nm spectral region. Tumors were also imaged by use of contrast-enhanced magnetic resonance imaging (MRI) and coregistered with the location of the optical probe. The absolute concentrations of contrast agent, oxyhemoglobin, deoxyhemoglobin, and water are measured simultaneously each second for approximately 10 min. The differing tissue uptake kinetics of ICG and MB in these late-stage tumors arise from differences in their effective molecular weights. ICG, because of its binding to plasma proteins, behaves as a macromolecular contrast agent with a low vascular permeability. A compartmental model describing ICG dynamics is used to quantify physiologic parameters related to capillary permeability. In contrast, MB behaves as a small-molecular-weight contrast agent that leaks rapidly from the vasculature into the extravascular, extracellular space, and is sensitive to blood flow and the arterial input function.

Adenocarcinoma↗

PubMed2003

Coregistration of diffuse optical spectroscopy and magnetic resonance imaging in a rat tumor model.

We report coregistration of near-infrared diffuse optical spectroscopy (DOS) and magnetic resonance imaging (MRI) for the study of animal model tumors. A combined broadband steady-state and frequency-domain apparatus was used to determine tissue oxyhemoglobin, deoxyhemoglobin, and water concentration locally in tumors. Simultaneous MRI coregistration provided structural (T2-weighted) and contrast-enhanced images of the tumor that were correlated with the optical measurements. By use of Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, showing precisely which tissue structure was probed optically. DOS and MRI coregistration measurements were performed on seven rats over 20 days and were separated into three tumor tissue classifications: viable, edematous, and necrotic. A ratio of water concentration to total hemoglobin concentration, as measured optically, was performed for each tissue type and showed values for edematous tissue to be greater than viable tissue (1.2 +/- 0.49 M/microM versus 0.48 +/- 0.15 M/microM). Tissue hemoglobin oxygen saturation (StO2) also showed a large variation between tissue types: viable tissue had an optically measured StO2 value of 61 +/- 5%, whereas StO2 determined for necrotic tissue was 43 +/- 6%.

Adenocarcinoma↗

PubMed2003

Correlation of dynamic contrast enhancement MRI parameters with microvessel density and VEGF for assessment of angiogenesis in breast cancer.

PURPOSE: To investigate the association between parameters obtained from dynamic contrast enhanced MRI (DCE-MRI) of breast cancer using different analysis approaches, as well as their correlation with angiogenesis biomarkers (vascular endothelial growth factor and vessel density). MATERIALS AND METHODS: DCE-MRI results were obtained from 105 patients with breast cancer (108 lesions). Three analysis methods were applied: 1) whole tumor analysis, 2) regional hot-spot analysis, and 3) intratumor pixel-by-pixel analysis. Early enhancement intensities and fitted pharmacokinetic parameters were studied. Paraffin blocks of 71 surgically resected specimens were analyzed by immunohistochemical staining to measure microvessel counts (with CD31) and vascular endothelial growth factor (VEGF) expression levels. RESULTS: MRI parameters obtained from the three analysis methods showed significant correlations (P < 0.0001), but a substantial dispersion from the linear regression line was noted (r = 0.72-0.97). The entire region of interest (ROI) vs. pixel population analyses had a significantly higher association compared to the entire ROI vs. hot-spot analyses. Cancer specimens with high VEGF expression had significantly higher CD31 microvessel densities than did specimens with low VEGF levels (P < 0.005). No significant association was found between MRI parameters obtained from the three analysis strategies and IHC based measurements of angiogenesis. CONCLUSION: A consistent analysis strategy was important in the DCE-MRI study. In this series, none of these strategies yielded results for MRI based quantitation of tumor vascularity that were associated with IHC based measurements. Therefore, different analyses could not account for the lack of association.

Breast↗

PubMed2003

A simple simultaneous geometric and intensity correction method for echo-planar imaging by EPI-based phase modulation.

A technique, based on Echo planar imaging (EPI)-based phase modulation factor maps, is described for correction of EPI distortions resulting from field inhomogeneity. In this paper, a phase modulation factor was employed to remove the distortions. The phase modulation factor was obtained experimentally by collecting EPI images with a spin-echo (TE) spacing, deltaTE, equal to the inter-echo time interval, T(i). Then, the distortions resulting from the field inhomogeneity were removed by modulating the kappa-space data with the phase modulation factor. One of the advantages of this method is that it requires only a few extra scans to collect the information on field inhomogeneity. The proposed method does not require a phase unwrapping procedure for field inhomogeneity correction and, hence, is easier to implement, compared to other techniques. In addition, it corrects geometric distortion as well as intensity distortions simultaneously, which is robust to external noise or estimation error in severely distorted images. In this work, we also compared the proposed technique with others including, a) interpolation method with EPI-based displacement maps, and b) modulation method with phase modulation factor maps generated from spin-echo images. The results suggest the proposed technique is superior in correcting severely distorted images.

Algorithms↗

PubMed2003

Inhibition of thrombosis in melanoma allografts in mice by endogenous mast cell heparin.

An unexplained paradox of malignant melanoma is the apparent failure of the blood within the tumor to clot despite the presence of multiple factors that should promote blood clotting. Here we present histochemical evidence that human and murine melanomas are extensively infiltrated by abundant mast cells. Because mast cells contain the natural anticoagulant heparin, the present studies were aimed at defining the role of mast cell heparin in preventing the blood from clotting within B16 melanoma grafts in C57BL/6 J mice. Mice bearing B16 melanoma grafts were treated with non-specific or specific inhibitors of mast cell heparin (protamine or heparinase, respectively). After the drug treatment there was histologic and functional evidence of selective thrombosis of the blood vessels within the protamine and heparinase treated melanoma grafts. A similar, high degree of thrombosis was also observed in B16 tumors grown in transgenic NDST-2 knockout mice bearing a targeted disruption in the gene coding for mast cell heparin synthesis. The tumors grown in the protamine-treated animals were significantly smaller than the tumors from control (untreated mice). By contrast, the tumors treated with heparinase or grown in the NDST-2 knockout mice were significantly larger than the tumors from control (untreated) mice. We conclude that the intrinsic procoagulant properties of malignant melanoma are neutralized in vivo by the anticoagulant properties of endogenous heparin produced by mast cells that naturally infiltrate the tumor. Our results also suggest that thrombosis and hemostasis within melanoma may play a complex role in modulating the growth of the tumor.

Amidohydrolases↗