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1.
Conventional hyperthermia enhances tumor response to radiotherapy through thermal cell inactivation and vascular shut-down, whereas mild hyperthermia potentiates the effect of radiotherapy by improving tumor oxygenation. The work reported here was aimed at investigating whether 31P-magnetic resonance spectroscopy (31P-MRS) measurements of tumor bioenergetic status; i.e., the (PCr + NTPbeta)/Pi resonance ratio, and/or the spin lattice relaxation times, T1s, of the Pi and NTPbeta resonances can be used to distinguish between the effects of conventional and mild hyperthermia. BEX-t human melanoma xenografts were treated at 43.0 degrees C for 15 or 60 min, and bioenergetic status and T1s were measured as function-of-time after treatment. Hyperthermia-induced effects on tumor blood flow was measured by using the 86Rb uptake method. The morphology of the capillary network in treated and untreated tumors was studied by histologic examination. Tumors treated for 15 min showed increased blood flow and dilated capillaries, whereas tumors treated for 60 min showed decreased blood flow and capillary occlusions; i.e., 43.0 degrees C for 15 min was a treatment consistent with mild hyperthermia and 43.0 degrees C for 60 min was consistent with conventional hyperthermia treatment of BEX-t tumors. Bioenergetic status increased after treatment at 43.0 degrees C for 15 min, and decreased after treatment at 43.0 degrees C for 60 min, similar to the blood flow. Likewise, the T1 of the Pi resonance increased after treatment at 43.0 degrees C for 15 min, and decreased after treatment at 43.0 degrees C for 60 min. The T1 of the NTPbeta resonance showed a similar change as the T1 of the Pi resonance, but less pronounced. Consequently, 31P-MRS measurements of tumor bioenergetic status and the T1 of the Pi resonance may perhaps be utilized to distinguish between vascular effects of mild and conventional hyperthermia.  相似文献   

2.
In the last years, hyperthermia induced by the heating of magnetic nanoparticles (MNPs) in an alternating magnetic field received considerable attention in cancer therapy. The thermal effects could be automatically controlled by using MNPs with selective magnetic absorption properties. In this paper, we analyze the temperature field determined by the heating of MNPs, injected in a malignant tissue, subjected to an alternating magnetic field. The main parameters which have a strong influence on temperature field are analyzed. The temperature evolution within healthy and tumor tissues are analyzed by finite element method (FEM) simulations in a thermo-fluid model. The cooling effect produced by blood flow in blood vessels from the tumor is considered. A thermal analysis is conducted under different distributions of MNP injection sites. The interdependence between the optimum dose of the nanoparticles and various types of tumors is investigated in order to understand their thermal effect on hyperthermia therapy. The control of the temperature field in the tumor and healthy tissues is an important step in the healing treatment.  相似文献   

3.
Rabbit liver was loaded with ferrimagnetic particles of gamma -Fe2 O3 (designed for magnetic hyperthermia treatment of liver tumors) by injecting various doses of a suspension of the particles into the hepatic artery in vivo. Proton transverse relaxation rate (R(2)) images of the livers in vivo, excised, and dissected were generated from a series of single spin-echo images. Mean R(2) values for samples of ferrimagnetic-particle-loaded liver dissected into approximate 1 cm cubes were found to linearly correlate with tissue iron concentration over the range from approximately 0.1 to at least 2.7 mg Fe/g dry tissue when measured at room temperature. Changing the temperature of ferrimagnetic-particle-loaded samples of liver from 1 degrees C to 37 degrees C had no observable effect on tissue R(2) values. However, a small but significant decrease in R(2) was found for control samples containing no ferrimagnetic material on raising the temperature from 1 degrees C to 37 degrees C. Both chemically measured iron concentrations and mean R(2) values for rabbit livers with implanted tumors tended to be higher than those measured for tumor-free liver. This study indicates that tissue R(2) measurement and imaging by nuclear magnetic resonance may have a useful role in magnetic hyperthermia therapy protocols for the treatment of liver cancer.  相似文献   

4.
Abstract  Heating tumors by nanoparticles and resistance in hypoxic tumor cells to a high temperature is emerging as an effective tool in therapeutic oncology as nanomedicine tool. The art of imaging temperature in a tumor at various locations is emerging as the selective approach of hyperthermia to monitor temperature and treat the tumor. However, thermometry and tumor cell interaction with nanoparticles may monitor and evaluate the tumor cell survival after exposure to high physiological temperatures. The application of 10–100 nanometer sized nanoparticles in tumor hyperthermia has emerged as an effective monitoring tool as magnetic resonance (MR) thermal mapping. The temperature and nanoparticle magnetic moment relationship is specific. Furthermore, there are two main issues that are unsolved as of yet. First issue is the relationship of tumor energy changes due to tumor magnetization; linear attenuation after magnetic field and X-ray exposure with tissue temperature increase. The second issue is the undefined behavior of the nanoparticle inside the tumor as diamagnetic or paramagnetic can be therapeutic and it depends on the tumor tissue temperature. In vivo imaging such as MR thermometry mapping of different hypoxic tumor locations solves these issues to some extent. The art of the nanoparticle-induced hyperthermia does have a great impact on public health as alternative therapeutic oncology. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.  相似文献   

5.
The present experiments were conducted to determine the effects of dexamethasone mediated changes in tumor water distribution on proton relaxation times (T1, T2) in a murine pancreatic adenocarcinoma (Panc02). Spin lattice (T1) and spin-spin (T2) relaxation times were determined by ex vivo methods (10MHz) and by in vivo imaging techniques (6.25 MHz) at various intervals after single or multiple dexamethasone treatments. In complementary studies, dexamethasone mediated changes in tumor capillary permeability, tumor water distribution, relative tumor blood flow and tumor cell proliferation were also determined.

Proton spin lattice (T1) and spin-spin (T2 relaxation times for Panc02 tumors shortened within two hours of a single dexamethasone treatment. The time course and magnitude of this response was dexamethasone dose dependent. The time dependent changes in T1 and T2 after dexamethasone were similar at 10 MHz (ex vivo) and 6.25 MHz (in vivo imaging). Although dexamethasone produced little or no change in total tumor water content and tumor cell proliferation, transient changes in the physiologic distribution of tumor water were clearly demonstrated.

The data supports the idea that dexamethasone induced changes in the distribution of tumor water were mediated by changes in capillary permeability and tumor blood flow. These physiologic responses produced serial changes in tumor extracellular extravascular water content that were consistent with the observed changes in tumor T1 and T2. The results from these experiments might imply that therapy associated changes in tumor proton relaxation times may not only reflect changes in tissue water content, but may also reflect physiologic responses which alter the distribution of tissue water and solute.  相似文献   


6.
Invasiveness of temperature monitoring devices is presently one of the most serious limitations to the application of oncological hyperthermia (HT). A promising approach aims at detecting temperature variations by monitoring the mean grey level (MGL) of the ultrasonographic image of the tissue. Gaseous ultrasound contrast agents (UCA), enhancing Ultrasonic (US) imaging, are expected to be sensitive to temperature, and are therefore a good candidate as temperature monitoring medium. The present study evaluates the 'in vitro' temporal and thermal stability and the correlation between temperature and MGL using a gaseous UCA (SonoVue) as phantom. No statistical differences were detected between the MGL value of the phantom kept at 43.5 degrees C before (215.2+/-3.5) and after 1 h (214.8+/-2.5), showing good stability at HT temperatures. Data of MGL image vs. temperature were obtained during both heating and cooling experiments in the HT range (30-43 degrees C). A good linearity of MGL vs. temperature (R2=0.976) was found with a good accuracy (2.5%) and a sensitivity of about 6.6 MGL/degrees C.  相似文献   

7.
In this work, the activation of heat-sensitive trans-gene by high-intensity focused ultrasound (HIFU) in a tumor model was investigated. 4T1 cancer cells (2 x 10(6)) were inoculated subcutaneously in the hind limbs of Balb/C mice. The tumors were subsequently transducted on day 10 by intratumoral injection of a heat-sensitive adenovirus vector (Adeno-hsp70B-Luc at 2 x 10(8) pfu/tumor). On day 11, the tumors were heated to a peak temperature of 55, 65, 75, or 85 degrees C within 10-30 s at multiple sites around the center of the tumor by a 1.1- or 3.3-MHz HIFU transducer. Inducible luciferase gene expression was increased from 15-fold to 120-fold of the control group following 1.1-MHz HIFU exposure. Maximum gene activation (120-fold) was produced at a peak temperature of 65-75 degrees C one day following HIFU exposure and decayed to baseline within 7 days. HIFU-induced gene activation (75 degrees C-10 s) could be further improved by using a 3.3-MHz transducer and a dense scan strategy to 170-fold. Thermal stress, rather than nonthermal mechanical stress, was identified as the primary physical mechanism for HIFU-induced gene activation in vivo. Overall, these observations open up the possibility for combining HIFU thermal ablation with heat-regulated gene therapy for cancer treatment.  相似文献   

8.
Hyperthermic temperatures, with potential applications in drug/gene delivery and chemo/radio sensitization, may be generated in biological tissues by applying focused ultrasound (FUS) in pulsed mode. Here, a strategy for optimizing FUS exposures for hyperthermia applications is proposed based on theoretical simulations and in vitro experiments. Initial simulations were carried out for tissue-mimicking phantoms, and subsequent thermocouple measurements allowed for validation of the simulation results. Advanced simulations were then conducted for an ectopic, murine xenograft tumor model. The ultrasound exposure parameters investigated in this study included acoustic power (3-5 W), duty cycle (DC) (10%-50%), and pulse repetition frequency (PRF) (1-5 Hz), as well as effects of tissue perfusion. The thermocouple measurements agreed well with simulation outcomes, where differences between the two never exceeded 1.9%. Based on a desired temperature range of 39-44 °C, optimal tumor coverage (40.8% of the total tumor volume) by a single FUS exposure at 1 MHz was achieved with 4 W acoustic power, 50% DC, and 5 Hz PRF. Results of this study demonstrate the utility of a proposed strategy for optimizing pulsed-FUS induced hyperthermia. These strategies can help reduce the requirement for empirical animal experimentation, and facilitate the translation of pulsed-FUS applications to the clinic.  相似文献   

9.
Lierke EG  Hemsel T 《Ultrasonics》2006,44(Z1):e341-e344
An improved concept for ultrasonic hyperthermia of tumors is presented. This concept is based on past experience of a German government supported project , which ended in 1984. It offers a low cost alternative to common RF- and microwave methods for hyperthermia of tumors with volumes between 1 and 40 ml at treatment times between 30 and 60 min. Our new version of the system considerably improves the temperature suppression in the healthy tissue around the target area and enables the adjustment of the beam width to the actual tumor size and the field geometry to the depth and shape of the tumor. The applicator can be used for moderate hyperthermia with tissue overheating up to 10K or for ablation therapy with short high temperature pulses. Its central area is free for the integration of a commercial ultrasonic diagnostic sector scanner or a Doppler flow sensor in order to support the adjustment of the transducer and to monitor the whole area during the therapy.  相似文献   

10.
It has been previously shown that the amplitude of the ultrasound-stimulated acoustic emission (USAE) signal is sensitive to tissue temperature and, therefore, can help detect it. Its amplitude, however, is sensitive to both acoustical and mechanical parameters, that at most frequencies have opposite effects due to temperature. In this paper, we explore the feasibility of using a frequency shift of the resonant peaks of the USAE signal for monitoring the tissue stiffness variation with temperature. In a numerical simulation, the variation of the frequency shift at different temperatures is shown. Then, in a series of experiments involving a gel phantom and porcine muscle tissue, the frequency shift variation is shown to follow the known stiffness changes due to temperature. It is also shown that this shift indicates reversible changes as well as the onset of thermal coagulative necrosis. The necrosis is marked by a monotonically increasing positive frequency shift. It was thus shown that the USAE spectrum peaks undergo a negative shift (or, downshift) when the stiffness decreases and a positive shift (or, upshift) when the stiffness increases. The experimental frequency shifted around a peak at 22.1-22.5 kHz within a range of -250 to 80 Hz and -200 to 250 Hz for the gel and muscle tissue for the temperatures of 25-70 and 30-70 degrees C, respectively. Simulation and ex vivo experimental results indicate that the USAE frequency shift method can help decouple the mechanical from the acoustical parameter dependence as well as detect the onset of thermal coagulative necrosis.  相似文献   

11.
Accurate measurement of tissue relaxation characteristics is dependent on many factors, including field strength and temperature. The purpose of this study was to evaluate the relationship between sample temperature, viscosity and proton spin-lattice relaxation time (T1) and spin-spin relaxation time (T2). A review of two basic models of relaxation the simple molecular motion model and the fast exchange two state model is given with reference to their thermal dependencies. The temperature dependence for both T1 and T2 was studied on a 0.15 Tesla whole body magnetic resonance imager. Thirteen samples comprising both simple and complex materials were investigated by using a standard spin-echo (SE) technique and a modified Carr-Purcell-Meiboom-Gill (CPMG) multi-echo sequence. A simple linear relationship between T1 and temperature was observed for all samples over the range of 20 degrees C to 50 degrees C. There is an inverse relationship between viscosity and T1 and T2. A quantity called the temperature dependence coefficient (TDC) is introduced and defined as the percent rate of change of the proton relaxation time referenced to a specific temperature. The large TDC found for T1 values, e.g. 2.37%/degrees C for CuSO4 solutions and 3.59%/degrees C for light vegetable oils at 22 degrees C, indicates that a temperature correction should be made when comparing in-vivo and in-vitro T1 times. The T2 temperature dependence is relatively small.  相似文献   

12.
In vivo magnetic resonance imaging (MRI) and angiography were applied to the marine spider crab Maja squinado for a study of temperature effects and thermal tolerance. Ventilation and haemolymph circulation were investigated during progressive cooling from 12 degrees C to 2 degrees C. The anatomical resolution of MR images from Maja squinado obtained with a standard spin echo sequence were suitable to resolve the structures of various internal organs. The heart of the animal could be depicted without movement artifacts. The use of a flow compensated gradient echo sequence allowed simultaneous observations of ventilation, reflected by water flow through the gill chambers as well as of haemolymph flow. Simultaneous investigation of various arteries was possible by use of flow weighted MRI. In addition to those accessible by standard invasive flow sensitive doppler sensors, flow changes in gill, leg arteries and the venous return could be observed. Both ventilation and haemolymph flow decreased during progressive cooling and changes in haemolymph flow varied between arteries. Haemolymph flow through the Arteria sternalis, some gill and leg arteries was maintained at low temperatures indicating a reduced thermal sensitivity of flow in selected vessels. In support of previous invasive studies of haemolymph flow as well as heart and ventilation rates, the results demonstrate that the operation of gills and the maintenance of locomotor activity are critical for cold tolerance. A shift in haemolymph flow between arteries likely occurs to ensure the functioning of locomotion and ventilation in the cold.  相似文献   

13.
Magnetic fluid hyperthermia (MFH) is a cancer treatment that can selectively elevate the tumor temperature without significantly damaging the surrounding healthy tissue. Optimal MFH design requires a fundamental parametric investigation of the heating of soft materials by magnetic fluids. We model the problem of a spherical tumor and its surrounding healthy tissue that are heated by exciting a homogeneous dispersion of magnetic nanoparticles infused only into the tumor with an external AC magnetic field. The key dimensionless parameters influencing thermotherapy are the Péclet, Fourier, and Joule numbers. Analytical solutions for transient and steady hyperthermia provide correlations between these parameters and the portions of tumor and healthy tissue that are subjected to a threshold temperature beyond which they are damaged. Increasing the ratio of the Fourier and Joule numbers also increases the tumor temperature, but doing so can damage the healthy tissue. Higher magnetic heating is required for larger Péclet numbers due to the larger convection heat loss that occurs through blood perfusion. A comparison of the model predictions with previous experimental data for MFH applied to rabbit tumors shows good agreement. The optimal MFH conditions are identified based on two indices, the fraction IT of the tumor volume in which the local temperature is above a threshold temperature and the ratio IN of the damaged normal tissue volume to the tumor tissue volume that also lies above it. The spatial variation in the nanoparticle concentration is also considered. A Gaussian distribution provides efficacy while minimizing the possibility of generating a tumor hot spot. Varying the thermal properties of tumor and normal tissue alters ITand IN but the nature of the temperature distribution remains unchanged.  相似文献   

14.
The objective of this study was to investigate MRI methods for monitoring focused ultrasound surgery (FUS) of breast tumors. To this end, the mammary glands of sheep were used as tissue model. The tissue was treated in vivo with numerous single sonications which covered extended target volumes by employing a scanning technique. The ultrasound focus position was controlled by online temperature mapping based on the temperature dependence of the relaxation time T(1). This approach proved to be reliable and offers thus an alternative to proton resonance frequency methods, whose application is hampered in fatty tissues. FUS-induced tissue changes were visible on T(2)- as well as on pre- and post-contrast T(1)-weighted images. According to our initial experience, noninvasive MRI-guided FUS of breast tumors is feasible.  相似文献   

15.
Sequential T1 changes in brain tumor tissue after Gd-DTPA administration were investigated in 10 patients, including 4 meningiomas, 2 gliomas, 3 metastatic cerebral tumors and 1 brain abscess. T1 values were measured serially for 60 minutes following Gd-DTPA injection using a magnetic focusing technique. In vitro T1 of the whole blood samples was also comparatively examined. Time processes in the tissue-blood ratio (TBR) were calculated from two-point relaxation rates at 5 and 30 minutes. The obtained ratios of TBR were ranged from 1.0 to 3.0, probably depending on histological types of brain tumor (the value of 1.0 to 1.5 for meningioma and 1.5 to 3.0 for glioma and metastatic tumor). No significant changes in the T1 value were observed in the examined normal tissue and peritumoral edema. These results indicate that Gd-DTPA plays an important role not only as an image enhancer for tumor tissue but also as an indicator for estimating the blood-brain barrier function.  相似文献   

16.
Functional magnetic resonance imaging (MRI) with a new intravascular contrast agent, monocrystalline iron oxide nanoparticles (MION), was applied to assess the effect of transpupillary thermotherapy in a rabbit model of choroidal melanoma. 3D-spoiled gradient recalled sequences were used for quantitative assessment of blood volume. The MRI-parameters were 5/22/35 degrees (time of repetition (TR)/echo delay (TE)/flip angle (FA)) for T(1)- and 50/61/10 degrees for T(2)-weighted sequences. Images were collected before and at different times after MION injection. In all untreated tissues studied, MION reduced the T(2)-weighted signal intensity within 0.5 h and at 24 h (all p <== 0.012), whereas no significant changes were detected in treated tumors. T(1)-weighted images also revealed differences of MION-related signal changes between treated tumors and other tissues, yet at lower sensitivity and specificity than T(2). The change of T(2)-weighted MRI signal caused by intravascular MION allows early distinction of laser-treated experimental melanomas from untreated tissues. Further study is necessary to determine whether MRI can localize areas of tumor regrowth within tumors treated incompletely.  相似文献   

17.
Gradient recalled echo (GRE) images are sensitive to both paramagnetic deoxyhaemoglobin concentration (via T2*) and flow (via T1*). Large GRE signal intensity increases have been observed in subcutaneous tumors during carbogen (5% carbon dioxide, 95% oxygen) breathing. We term this combined effect flow and oxygenation-dependent (FLOOD) contrast. We have now used both spin echo (SE) and GRE images to evaluate how changes in relaxation times and flow contribute to image intensity contrast changes. T1-weighted images, with and without outer slice suppression, and calculated T2, T2* and "flow" maps, were obtained for subcutaneous GH3 prolactinomas in rats during air and carbogen breathing. T1-weighted images showed bright features that increased in size, intensity and number with carbogen breathing. H&E stained histological sections confirmed them to be large blood vessels. Apparent T1 and T2 images were fairly homogeneous with average relaxation times of 850 ms and 37 ms, respectively, during air breathing, with increases of 2% for T1 and 11% for T2 during carbogen breathing. The apparent T2* over all tumors was very heterogeneous, with values between 9 and 23 ms and localized increases of up to 75% during carbogen breathing. Synthesised "flow" maps also showed heterogeneity, and regions of maximum increase in flow did not always coincide with maximum increases in T2*. Carbogen breathing caused a threefold increase in arterial rat blood PaO2, and typically a 50% increase in tumor blood volume as measured by 51Cr-labelled RBC uptake. The T2* increase is therefore due to a decrease in blood deoxyhaemoglobin concentration with the magnitude of the FLOOD response being determined by the vascular density and responsiveness to blood flow modifiers. FLOOD contrast may therefore be of value in assessing the magnitude and heterogeneity of response of individual tumors to blood flow modifiers for both chemotherapy, antiangiogenesis therapy in particular, and radiotherapy.  相似文献   

18.
Temperature control of hyperthermia treatments is generally implemented with multipoint feedback system comprised of phased-array transducer, which is complicated and high cost. Our simulations to the acoustic field induced by a self-focused concave spherical transducer (0.5 MHz, 9 cm aperture width, 8.0 cm focal length) show that the distribution of temperature can keep the same “cigar shape” in the focal region during ultrasound insonation. Based on the characteristic of the temperature change, a two-dimensional model of a “cigar shape” tumor is designed and tested through numerical simulation. One single-point on the border of the “cigar shape” tumor is selected as the control target and is controlled at the temperature of 43 °C by using a self-tuning regulator (STR). Considering the nonlinear effects of biological medium, an accurate state-space model obtained via the finite Fourier integral transformation to the bioheat equation is presented and used for calculating temperature. Computer simulations were performed with the perfusion rates of 2.0 kg/(m3 s) and 4.5 kg/(m3 s) to the different targets, it was found that the temperatures on the border of the “cigar shape” tumor can achieve the desired temperature of 43 °C by control of one single-point. A larger perfusion rate requires a higher power output to obtain the same temperature elevation under the same insonation time and needs a higher cost for compensating the energy loss carried away by blood flow after steady state. The power output increases with the controlled region while achieving the same temperature at the same time. Especially, there is no overshoot during temperature elevation and no oscillation after steady state. The simulation results demonstrate that the proposed approach may offers a way for obtaining a single-point, low-cost hyperthermia system.  相似文献   

19.
Faraday surface instability measurements of the critical acceleration, a(c), and wave number, k(c), for standing surface waves on a tetracosanol (C24H50) melt exhibit abrupt changes at T(s)=54 degrees C, approximately 4 degrees C above the bulk freezing temperature. The measured variations of a(c) and k(c) vs temperature and driving frequency are accounted for quantitatively by a hydrodynamic model, revealing a change from a free-slip surface flow, generic for a free liquid surface (T>T(s)), to a surface-pinned, no-slip flow, characteristic of a flow near a wetted solid wall (T相似文献   

20.
The efficacy of ultrasound-assisted thrombolysis as an adjunct treatment of ischemic stroke is being widely investigated. To determine the role of ultrasound hyperthermia in the process of blood clot disruption, the acousto-mechanical and thermal properties of clotted blood were measured in vitro, namely, density, speed of sound, frequency-dependent attenuation, specific heat, and thermal conductivity. The amplitude coefficient of attenuation of the clots was determined for 120 kHz, 1.0 MHz, and 3.5 MHz ultrasound at room temperature (20 +/- 2 degrees C). The attenuation coefficient ranged from 0.10 to 0.30 Np/cm in porcine clots and from 0.09 to 0.23 Np/cm in human clots. The experimentally determined values of specific heat and thermal conductivity for porcine clotted blood are (3.2 +/- 0.5) x 10(3) J/kg x K and 0.55 +/- 0.13 W/m x K, respectively, and for human clotted blood are (3.5 +/- 0.8) x 10(3) J/kg x K and 0.59 +/- 0.11 W/m x K, respectively. Measurements of the acousto-mechanical and thermal properties of clotted blood can be helpful in theoretical modeling of ultrasound hyperthermia in ultrasound-assisted thrombolysis and other high-intensity focused ultrasound applications.  相似文献   

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