Koichi Shibuya

Development of a tissue-equivalent MRI phantom using carrageenan gel.

A new tissue‐equivalent MRI phantom based on carrageenan gel was developed. Carrageenan gel is an ideal solidifying agent for making large, strong phantoms in a wide variety of shapes. GdCl3 was added as a T1 modifier and agarose as a T2 modifier. The relaxation times of a very large number of samples were estimated using 1.5‐T clinical MRI equipment. The developed phantom was found to have a T1 value of 202–1904 ms and a T2 value of 38–423 ms when the GdCl3 concentration was varied from 0–140 μmol/kg and the agarose concentration was varied from 0–1.6% in a carrageenan concentration that was fixed at 3%. The range of measured relaxation times covered those of all types of human tissue. Empirical formulas linking the relaxation time with the concentration of the modifier were established to enable the accurate and easy calculation of the modifier concentration needed to achieve the required relaxation times. This enables the creation of a phantom having an arbitrary combination of T1 and T2 values and which is capable of retaining its shape. Magn Reson Med 50:1011–1017, 2003.

Composition of MRI phantom equivalent to human tissues.

We previously developed two new MRI phantoms (called the CAG phantom and the CAGN phantom), with T1 and T2 relaxation times equivalent to those of any human tissue at 1.5 T. The conductivity of the CAGN phantom is equivalent to that of most types of human tissue in the frequency range of 1 to 130 MHz. In this paper, the relaxation times of human tissues are summarized, and the composition of the corresponding phantoms are provided in table form. The ingredients of these phantoms are carrageenan as the gelling agent, GdCl3 as a T1 modifier, agarose as a T2 modifier, NaCl (CAGN phantom only) as a conductivity modifier, NaN3 as an antiseptic, and distilled water. The phantoms have T1 values of 202-1904 ms and T2 values of 38-423 ms when the concentrations of GdCl3 and agarose are varied from 0-140 micromol/kg, and 0%-1.6%, respectively, and the CAGN phantom has a conductivity of 0.27-1.26 S/m when the NaCl concentration is varied from 0%-0.7%. These phantoms have sufficient strength to replicate a torso without the use of reinforcing agents, and can be cut by a knife into any shape. We anticipate the CAGN phantom to be highly useful and practical for MRI and hyperthermia-related research.

Development of MRI phantom equivalent to human tissues for 3.0‐T MRI

PURPOSE A 3.0-T MRI phantom (called the CAGN-3.0T phantom) having human-equivalent relaxation times and human-equivalent conductivity was developed. METHODS The ingredients of the phantom are carrageenan (as a gelatinizer), agarose (as a T2-relaxation modifier), GdCl3 (as a T1-relaxation modifier), NaCl (as a conductivity modifier), and NaN3 (as an antiseptic). Numerous samples with varying concentrations of agarose, GdCl3, and NaCl were prepared, and T1 and T2 values were measured using 3.0-T MRI. RESULTS The T1 values of the CAGN-3.0T phantom were unaffected by NaCl, while the T2 values were only slightly affected. Based on the measured data, empirical formulae were devised to express the relationships between the concentrations of agarose, GdCl3, and NaCl and the relaxation times. The formula for expressing the conductivity of the CAGN-3.0T phantom was obtained. CONCLUSIONS By adjustments to the concentrations of agarose, GdCl3, and NaCl, the relaxation times and conductivity of almost all types of human tissues can be simulated by CAGN-3.0T phantoms. The phantoms have T1 values of 395-2601 ms, T2 values of 29-334 ms, and conductivity of 0.27-1.26 S/m when concentrations of agarose, GdCl3, and NaCl are varied from 0 to 2.0 w/w%, 0 to 180 μmol/kg, and 0 to 0.7 w/w%, respectively. The CAGN-3.0T phantom has sufficient strength to replicate the torso without using reinforcing agents, and can be cut with a knife into any shape.

Development of a human-tissue-like phantom for 3.0-T MRI.

PURPOSE A 3.0-T MRI phantom having human-tissue-equivalent relaxation times was developed. METHODS The ingredients of the phantom are carrageenan (for gelatinization), GdCl(3) (as a T(1)-relaxation modifier), agarose (as a T(2)-relaxation modifier), and NaN(3) (as an antiseptic agent). Numerous samples with varying concentrations of GdCl(3) and agarose were prepared, and T(1) and T(2) were measured using 3.0-T MRI. RESULTS Relaxation times of the phantom samples ranged from 395 to 2601 ms for T(1) values and 29 to 334 ms for T(2) values. Based on the measured results, empirical formulae were devised to express the relationships between the concentrations of relaxation modifiers and relaxation times. CONCLUSIONS Adjustment of GdCl(3) and agarose concentrations allows arbitrary setting of relaxation times, and the creation of a phantom that can mimic relaxation times of human-tissue. Carrageenan is considered the most suitable as a gelling agent for an MRI phantom, as it permits the relatively easy and inexpensive production of a large phantom such as for the human torso, and which can be easily shaped with a knife.

Development of a phantom compatible for MRI and hyperthermia using carrageenan gel—relationship between T1 and T2 values and NaCl concentration

The authors developed a phantom, designated as the CAGN phantom, compatible for MRI and hyperthermia that is useful in the fundamental studies of non-invasive MR thermometry. The ingredients of this phantom are carrageenan, GdCl3 as a T1 modifier, agarose as a T2 modifier, NaCl as a conductivity modifier, NaN3 as an antiseptic and distilled water. Another phantom that was developed, the CAG phantom, has relaxation times that are adjustable to those of any human tissue. To use this phantom for electromagnetic heating, NaCl was added to change the conductivity of the phantom and clarified the relationship between the conductivity and NaCl concentration. This study examined the relationship between relaxation times and NaCl concentration of the CAGN phantom. The results showed that both T1 and T2 values were affected by NaCl and the experimental results led to the empirical formulae expressing the relationship between the relaxation rates (1/T1, 1/T2) and the concentrations of GdCl3, agarose and NaCl. The appropriate concentrations of T1 and T2 modifiers were calculated from these empirical formulae when making a specified phantom that has the required relaxation times and NaCl concentration.

Development of a phantom compatible for MRI and hyperthermia using carrageenan gel--relationship between dielectric properties and NaCl concentration.

A phantom has previously been developed containing carrageenan, agarose and gadolinium chloride (called CAG phantom) for MRI with 1.5 T. T1 and T2 relaxation times of this phantom are independently changeable by varying concentrations of relaxation-time modifiers to simulate relaxation times of the various types of human tissues. The CAG phantom has a T1 value of 202–1904 ms and a T2 value of 38–423 ms, when the GdCl3 concentration is varied from 0–140 µmol/kg and the agarose concentration is varied from 0–1.6%. A new phantom has now been developed (called CAGN phantom), made by adding an electric conductive agent, NaCl, to the CAG phantom for use in the areas of MRI and hyperthermia research. Dielectric properties of the CAGN phantom were measured and the results of experiments were expressed by the Cole–Cole equation in the frequency range of 5–130 MHz. The relationship between the conductivity of the CAGN phantom and the concentration of NaCl was expressed by a linear function in the frequency range of 1–130 MHz. The linear function involves a parameter of frequency and, when the frequency is 10 MHz, the conductivity of the CAGN phantom can be changed from 0.27–1.26 Sm−1 by increasing the NaCl concentration from 0–0.7%. The CAGN phantom developed can be employed in basic experiments for non-invasive temperature measurement using MRI and as a loading phantom for MRI with up to 3 T.

Effects of PKC inhibitors on suppression of thermotolerance development in tsAF8 cells

EŒects of protein kinase C (PKC) inhibitors (H7, staurosporine, calphostin C) on thermotolerance development were investigated in temperature sensitive tsAF8 cells derived from Syrian hamster BHK21 cells. Cells were pre-heated at 458C for 20 min, incubated at 348C with PKC inhibitors for varying lengths of time, i.e. 1.25± 10.0 h, and then heated at 458C for 30 min. Increasing survival fractions after the second heat treatment was inhibited by the treatment with H7 (40± 160 mM), with staurosporine (0.05± 1.0 mM), and with calphostin C (0.8, 1.2 mM) in a concentration dependent manner. When the concentrations of these PKC inhibitors were low, the restraint of increasing survival fractions was temporary, since survival fractions increased 3± 7.5 h after pre-heating. However, the survival fractions were almost constant by the treatment with 160 mM H7 and 1.0 mM staurosporine. Induction of HSP72 after heat stress was investigated in tsAF8 and BHK21 cells. Cells were heated at 458C for 20 min and incubated at 34 or 39.78C (tsAF8), at 378C (BHK21). Intensity of intracellular ̄ uorescence from HSP72 was measured by ̄ ow cytometry. HSP72 was induced in BHK21 cells, but there was no de® nite induction of HSP72 in tsAF8 cells at either 39.7 or 348C. These results suggest that PKC is related with the thermotolerance development in tsAF8 cells; however, HSP72 is not involved in the thermotolerance development in tsAF8 cells.Effects of protein kinase C (PKC) inhibitors (H7, staurosporine, calphostin C) on thermotolerance development were investigated in temperature sensitive tsAF8 cells derived from Syrian hamster BHK21 cells. Cells were pre-heated at 45 degrees C for 20 min, incubated at 34 degrees C with PKC inhibitors for varying lengths of time, i.e. 1.25-10.0 h, and then heated at 45 degrees C for 30 min. Increasing survival fractions after the second heat treatment was inhibited by the treatment with H7 (40-160 microM), with staurosporine (0.05-1.0 microM), and with calphostin C (0.8, 1.2 microM) in a concentration dependent manner. When the concentrations of these PKC inhibitors were low, the restraint of increasing survival fractions was temporary, since survival fractions increased 3-7.5 h after pre-heating. However, the survival fractions were almost constant by the treatment with 160 microM H7 and 1.0 microM staurosporine. Induction of HSP72 after heat stress was investigated in tsAF8 and BHK21 cells. Cells were heated at 45 degrees C for 20 min and incubated at 34 or 39.7 degrees C (tsAF8), at 37 degrees C (BHK21). Intensity of intracellular fluorescence from HSP72 was measured by flow cytometry. HSP72 was induced in BHK21 cells, but there was no definite induction of HSP72 in tsAF8 cells at either 39.7 or 34 degrees C. These results suggest that PKC is related with the thermotolerance development in tsAF8 cells; however, HSP72 is not involved in the thermotolerance development in tsAF8 cells.

Inhibition of thermotolerance observed on tsAF8 cells

The characteristic development of thermotolerance was examined in tsAF8 cells, which were temperature sensitive cell line derived from BHK21. tsAF8 cells lose RNA polymerase II activity and arrest in the G1 phase of the cell cycle at the nonpermissive temperature of 39.5-40.6°C. tsAF8 cells were pre-heated at 45°C for 20 min, incubated at 34 or 39.7°C for different durations, and then heated again at 45°C for 30 min. The cells were trypsinized immediately after the second heating to evaluate cell survival. As a result, thermotolerance was developed rapidly in the cells incubated at 34°C. However, the survival rate of the cells incubated at 39.7°C was almost constant. Thermotolerance of BHK21 cells, which were wild-type cells of tsAF8 cells, developed at 39.7°C. These results suggest that thermotolerance may be inhibited in tsAF8 cells incubated at 39.7°C, and that some metabolism which is inhibited in tsAF8 cells at 39.7°C may be related to thermotolerance development.

Recent Aspects of Elucidating the Cellular Basis of Thermochemotherapy

The cell-killing effects of some anticancer drugs are enhanced when accompanied by treatment with hyperthermia in vitro and in vivo. These effects are influenced by various environment conditions of tumor cells, such as pH, oxygen, and nutrition. An abiding problem is that multidrug-resistant cancer cells are often observed in the recurrent tumor after chemotherapy, but fortunately they have approximately equal sensitivity to hyperthermia as do wild-type cells. In addition, heating increases the influx of the anticancer drugs, thereby inducing a high level of intracellular accumulation. Recent reports on the mechanisms of anticancer drug enhancement via heating are reviewed.

Fundamental tests of pneumatic soft devices for pushing abdomen in stomach X-ray examination

This study aims at development of pneumatic soft devices for stomach X-ray examination. Generally stomach X-ray examination can be divided two procedures roughly. One is observation of condition of back-side stomach wall and the other is that of front-side stomach wall. In this paper, two types of soft devices for each examination have been developed. The devices are configured with pneumatic actuators which are radiolucent and soft, and realize compression of the abdomen. Volunteer tests were conducted using actual X-ray apparatus and these devices. The results indicate the potential of the devices to improve the conventional stomach X-ray examination.