Biomedical subjects

Orhan Nalcioglu

Publications and source records attributed to Orhan Nalcioglu.

27 records · Page 2Linked to original sources

PubMed2002

Assessment of protamine-induced thrombosis of tumor vessels for cancer therapy using dynamic contrast-enhanced MRI.

Since the role of angiogenesis in cancer development has been recognized, the study of anti-angiogenic or anti-vascular therapeutic agents has become increasingly important for cancer treatment. Selective thrombosis is one approach towards this goal. Since many types of carcinoma accumulate large numbers of degranulating mast cells which will release heparin, intravenously injected protamine may bind to heparin, neutralize its anti-coagulant effect and induce thrombosis. In this work we studied the formation of thrombosis by using dynamic contrast enhanced MRI. The enhancement kinetics of the contrast medium measured before and after protamine treatment were compared to assess the thrombotic effect. The underlying concept was that if the vessels became clotted, the subsequently injected contrast medium could not be delivered into the tissue to cause enhancement. In addition to the tissue-specific changes, protamine may also induce systemic effect in the host. The therapy-induced changes measured in tumors were compared to changes in normal tissues: liver, kidney, and especially the muscle adjacent to tumor. The results showed that protamine induced pronounced changes in the tumor. However, the degree of change measured by MRI was not associated with the results of semiquantitative assessment of thrombosis assessed by histology, perhaps due to the heterogeneous nature of the tumor and the difficulty in sampling sufficient regions histologically. The protamine-induced temporal effects were also studied. We demonstrated that protamine could induce selective thrombosis in tumors, and that the effect could last for several hours. Dynamic contrast-enhanced MRI can serve as a suitable means to investigate the mechanism of this novel approach to induce selective thrombosis for anti-vascular cancer therapy.

Adenocarcinoma↗

PubMed2002

Automatic tuned MRI RF coil for multinuclear imaging of small animals at 3T.

We have developed an MRI RF coil whose tuning can be adjusted automatically between 120 and 128 MHz for sequential spectroscopic imaging of hydrogen and fluorine nuclei at field strength 3 T. Variable capacitance (varactor) diodes were placed on each rung of an eight-leg low-pass birdcage coil to change the tuning frequency of the coil. The diode junction capacitance can be controlled by the amount of applied reverse bias voltage. Impedance matching was also done automatically by another pair of varactor diodes to obtain the maximum SNR at each frequency. The same bias voltage was applied to the tuning varactors on all rungs to avoid perturbations in the coil. A network analyzer was used to monitor matching and tuning of the coil. A Pentium PC controlled the analyzer through the GPIB bus. A code written in LABVIEW was used to communicate with the network analyzer and adjust the bias voltages of the varactors via D/A converters. Serially programmed D/A converter devices were used to apply the bias voltages to the varactors. Isolation amplifiers were used together with RF choke inductors to provide isolation between the RF coil and the DC bias lines. We acquired proton and fluorine images sequentially from a multicompartment phantom using the designed coil. Good matching and tuning were obtained at both resonance frequencies. The tuning and matching of the coil were changed from one resonance frequency to the other within 60 s.

Animals↗

PubMed2002

A double end-cap birdcage RF coil for small animal whole body imaging.

Proper design of a birdcage coil plays a very important role in obtaining high-resolution small animal magnetic resonance imaging. The RF field homogeneity and the coil filling factor directly affect the signal-to-noise ratio (S/N) and therefore limit the resolution. It has been shown that a conductive end-cap placed on one side of the coil can improve the RF field inhomogeneity near this area. This also contributes to an increase in the S/N by reducing the length of the RF coil. While this is true near the end-cap, the distal half of the coil still suffers from poor homogeneity and S/N. Consequently, such a shortfall may hinder small animal whole body imaging. In order to improve the coil performance for a larger imaging volume, we designed a new small animal birdcage RF coil by adding a detachable second end-cap to the open end. The performance of single end and double end RF coils was compared experimentally. The results indicate that the double end-cap can provide superior uniformity along the long axis of the coil. Furthermore, if one wishes to obtain the same homogeneity within a given volume, a double end-cap would have less than half of the length of the single end-cap coil leading to a superior S/N performance.

Animals↗

PubMed2002

Measurement of volumetric and vascular changes with dynamic contrast enhanced MRI for cancer therapy monitoring.

Longitudinal dynamic contrast enhanced MRI studies were undertaken to monitor therapy induced volumetric and vascular changes. Three study components are presented in this work: one animal tumor chemotherapy study (R3230 AC adenocarcinoma treated with Taxotere), one patient with invasive lobular breast cancer undergoing neoadjuvant chemotherapy (AC regimen), and one patient with brain metastasis of primary breast cancer undergoing radiation therapy (40 Gray whole brain irradiation). In the animal study two contrast media with different molecular weights, Gadodiamide and Gadomer-17, were used. Only Gadomer-17 revealed significant changes in vascular properties. The responders showed decreased V(b) (vascular volume index) and K(2) (out-flux transport rate), which preceded tumor regression. The control tumors showed increased V(b) and K(2), before tumor growth became much faster. In the patient undergoing neoadjuvant therapy, the tumor was shrinking by 45% after 2 cycles of treatment, then again by 45% after 2 additional cycles. K(2) was decreasing over time with treatment. In the patient with brain metastasis, the 2 follow-up studies were much longer apart to monitor the regression and relapse of lesions. The pre-treatment volumes of lesions in the group without recurrence were significantly smaller compared to those with recurrence. In summary, the tumor volume was more sensitive than the vascular parameters measured by the small extracellular contrast medium for the assessment of therapy response and prediction of recurrence. The vascular properties measured by macromolecular contrast medium may have the potential to serve as early therapeutic efficacy indicators.

Adenocarcinoma↗

PubMed2002

Congruent MRI and near-infrared spectroscopy for functional and structural imaging of tumors.

We present a combined near-infrared diffuse optical spectroscopy (DOS) and Magnetic Resonance Imaging (MRI) system for the study of animal model tumors. A combined broadband steady-state and frequency domain optical spectroscopy apparatus was integrated with the MRI. The physiological properties of tissue rendered by MRI, including vascular volume fraction and water, were compared with chromophore concentrations as determined from the parameters obtained by optical measurements. DOS measurements provided oxy-hemoglobin, deoxy-hemoglobin, and water concentration locally in tumors. A method for co-registration of the information obtained by both modalities was developed. Using Monte Carlo simulations, the optically sampled volume was superimposed on the MR images, illustrating which tissue structure was probed optically. Finally, two optical contrast agents, indocyanine green (ICG) and methylene blue (MB), were employed and their kinetics were measured by DOS system from different locations on the tumor and compared with Gd-DTPA enhancement maps obtained from MRI.

Animals↗

PubMed2002

A longitudinal study of radiation-induced changes in tumor vasculature by contrast-enhanced magnetic resonance imaging.

Dynamic contrast-enhanced MRI with two different-sized contrast agents, Gd-DTPA and Gadomer-17, was used to study the effects of radiation on the pharmacokinetics of the paramagnetic enhancement of water relaxation in the rat R3230 AC adenocarcinoma tumor model. The kinetics of enhancement was analyzed by a two-compartment pharmacokinetic model to derive parameters related to vascular volume (V(b)) and permeability (K(2)). Rats implanted with tumors were divided into two groups; one received 5 Gy and the other received 20 Gy (137)Cs gamma rays. Sequential dynamic contrast-enhanced MRI studies were performed, one before irradiation, one at day 1 after irradiation, and another at day 3 after irradiation, to investigate the effect of the radiation dose and the changes that occurred over time. The analysis was performed on a pixel-by-pixel basis to study the heterogeneity within the tumor. The pixel distribution profiles of V(b) and K(2) from each tumor were obtained to assess the regional radiation-induced effects on vascular volume and permeability. No significant change in vascular volume was detected with either Gd-DTPA or Gadomer-17 after irradiation of the tumor; however, a small dependence of K(2) on the radiation dose was observed. After low-dose (5 Gy) irradiation, the mean value of K(2) decreased by 46% at day 1 compared to the baseline, presumably due to cell swelling, and decreased further by 67% from the baseline on day 3. When the dose was increased to 20 Gy, the mean value of K(2) measured with Gadomer-17 did not show any significant changes at either day 1 or day 3 after irradiation. The value of K(2) measured with Gd-DTPA did not show any significant changes after either the low or the high radiation dose.

Adenocarcinoma↗

PubMed2002

Measuring microvascular density in tumors by digital dissection.

OBJECTIVE: To develop and validate a digital dissection techniquefor measuring the cross-sectional area of blood vessels in histologic sections of tumors routinely stained with hematoxylin and eosin. STUDY DESIGN: The procedure was first validated in four experimental tumors in rats by comparing the results of the digital dissection technique to functional estimates of the blood volume in the tumors as measured by dynamic, contrast-enhanced magnetic resonance imaging. The method was then tested on a variety of experimental and human tumors. RESULTS: The digital dissection technique yielded results that exactly matched the functional measurements of blood volume infour experimental tumors. Digital dissection of 40 additional tumors in rats showed that 21 infiltrating ductal carcinomas had significantly greater microvascular density (MVD) than 19 benign fibroadenomas (12% vs. 7.9%, P=.028 by two-tailed t test). In 10 human breast carcinomas the MVD was consistently greater than the measurement of blood vessel density as identified by immunohistochemical staining for factor VIII. The between-run coefficients of variation for the MVD assay were 12% (n = 5) for a human breast cancer and 18% (n = 5)for an experimental rat tumor. CONCLUSION: The digital dissection technique is a reproducible, objective and accurate method of measuring MVD in sections of tumors that are routinely stained with hematoxylin and eosin.

Albumins↗

PubMedDate not supplied

Design and implementation of a multifrequency near-infrared diffuse optical tomography system.

The design and implementation of a multifrequency and multispectral diffuse optical tomography system is described. Four wavelengths are utilized: 665, 785, 808, and 830 nm. The system is based on a network analyzer, which provides rf modulation signals for the laser diodes, as well as measures the amplitude and the phase of the detected signals. Six different modulation frequencies ranging from 110 to 280 MHz are used. The details of instrumentation, calibration, data acquisition, and performance of the system are given. 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. Data acquisition for one wavelength is completed in less than 2.5 min for a single modulation frequency. The measurement repeatability is 0.5% in ac intensity and 0.2 deg in phase. The performance of the system is evaluated with phantom studies. A multifrequency reconstruction algorithm is used, in which a single absorption and scattering image pair is obtained using the whole dataset obtained at different modulation frequencies. It is shown that the multifrequency reconstruction approach provides superior image quality compared to the single frequency counterpart.

Equipment Design↗

PubMedDate not supplied

Diffuse optical tomographic reconstruction using multifrequency data.

We investigated the use of multifrequency diffuse optical tomography (MF-DOT) data for the reconstruction of the optical parameters. The experiments were performed in a 63 mm diameter cylindrical phantom containing a 15 mm diameter cylindrical object. Modulation frequencies ranging from 110 MHz to 280 MHz were used in the phantom experiments changing the contrast in absorption of the object with respect to the phantom while keeping the scattering value the same. The diffusion equation was solved using the finite element method. The sensitivity information from each frequency was combined to form a single Jacobian. The inverse problem was solved iteratively by minimizing the difference between the measurements and forward problem using single and multiple modulation frequency data. A multiparameter Tikhonov scheme was used for regularization. The phantom results show that the peak absorption coefficient in a region of interest was obtained with an error less then 5% using two-frequency reconstruction for absorption contrast values up to 2.2 times higher than background and 10% for the absorption contrast values larger than 2.2. The use of two-frequency data is sufficient to improve the quantitative accuracy compared with the single frequency reconstruction with appropriate selection of these frequencies.

Algorithms↗