Influence of permittivity and electrical conductivity on image pattern of MRI.

In proton density-weighted (PDW) MR imaging, the patterns of signal intensity vary depending on the imaged material, and change with the flip angle (FA) applied to the imaged material. The correlation between the pre-determined FA and the actual FA applied to imaged objects was investigated using 4 types of phantoms having different dielectric properties. PDW images were acquired using the spin-echo (SE) method and different pre-determined FA. Dependency of the signal intensity distribution in the phantom on the pre-determined FA differed among phantoms: patterns for water and 0.402 w/w% saline solution phantoms changed with the pre-determined FA, whereas those for olive oil and 4.02 w/w% saline solution phantoms were barely affected by the pre-determined FA. Causes of these phenomena were considered to be the differences between the pre-determined FA and the actual FA among the phantoms; differences were also influenced by the positioning of the phantom. Our study showed that the actual FA in the phantom is greater than the pre-determined FA in high permittivity media, whereas it is reduced by an increased conductivity of the media.

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.

Rituximab used successfully in the treatment of anti-NMDA receptor encephalitis.

We report the case of a young woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, without tumor, who was successfully treated with rituximab. Because conventional immunotherapy, including corticosteroids, immunoglobulin (IVIg), and plasma exchange showed little improvement in our patient, we introduced another treatment using rituximab. A week after the first administration of rituximab, her symptoms improved gradually and significantly. This case provides in vivo evidence that rituximab is an effective agent for treating anti-NMDAR encephalitis, even in those cases where conventional immunotherapies have been ineffective. Rituximab should be regarded as a beneficial therapeutic agent for this disease.

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.

In vitro experimental study of the relationship between the apparent diffusion coefficient and changes in cellularity and cell morphology.

Diffusion-weighted magnetic resonance imaging (MRI) is frequently used clinically, and is available for the whole-body screening for tumors. The exact mechanism by which the apparent diffusion coefficient (ADC) value decreases in tumorous tissue remains unclear, although various theories have been proposed, including intracellular and extracellular factor theories. It is impossible to distinguish each factor in the intracellular and extracellular spaces as the source of MR signal generation by means of conventional comparison between MR images and pathological specimens. Other factors which have been reported to affect ADC include cellularity and cellular edema of human tissues, and temperature of phantoms at the time of measurement. We employed a new technique that enables cellular MR imaging using a newly developed bio-phantom containing a living culture tumor cell line, Jurkat-N1. We investigated possible reasons for observed decreases in ADC values for tumors, and we considered the contribution of both the intracellular and extracellular space to such a decrease. The ADC values of the bio-phantom increased with increasing heat exposure from 27 to 45 degrees C. ADC values also increased after the destruction by sonication of tumor cell membranes. ADC values decreased as cellularity increased in the bio-phantom. ADC values decreased due to cellular edema caused by a low salt concentration in the bio-phantom. Changes in pressure in the bio-phantom had no effect on the observed ADC values. We calculated both the intracellular ADC and extracellular ADC values using the ADC values, cellularity, and cellular volume of Jurkat-N1 cells in the bio-phantom. The extracellular ADC values in the bio-phantom were estimated to be lower than the ADC value of distilled water. These results indicate that not only intracellular ADC values, but also extracellular ADC values contribute to the determination of the ADC values of bio-phantoms. This is the first report to have examined the contribution of intracellular and extracellular space on the ADC values of bio-phantoms containing cultured tumor cells.

[Measurement of the air kerma using dosimeters embedded in an acrylic phantom in interventional radiology.].

Interventional radiology procedure guidelines and a measurement manual (IVR guidelines) have been published for the maintenance of interventional equipment with an objective of avoiding serious radiation-induced skin injuries. In the IVR guidelines, the positioning of a dosimeter at the interventional reference point is determined, whereas placement of a phantom is not specified. Therefore, the phantom is placed at any convenient location between the dosimeter and image intensifier. The space around the dosimeter reduces detection of scattered radiation. In this study, dosimeters (consisting of a parallel plate ionization chamber, glass dosimeter and OSL dosimeter) were embedded in the phantom surface to detected scattered radiation accurately. As a result, when dosimeters were embedded in the phantom surface, the air kerma was increased compared with that when dosimeters were placed on the phantom. This suggested that embedded dosimeters were able to detect scattered radiation from the phantom.

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 a new hybrid gel phantom using carrageenan and gellan gum for visualizing three-dimensional temperature distribution during hyperthermia and radiofrequency ablation.

We developed a new hybrid gel phantom using carrageenan and gellan gum for the purpose of visualizing three-dimensional temperature distribution. The phantom, which contains carrageenan, gellan gum, non-ionic surface active agent, potassium chloride, n-butanol, sodium azide, and water, shows good transparency at room temperature, and has the advantage that the heated region becomes white and opaque due to segregation of the surface active agent. Carrageenan and gellan gum were added to improve the transparency and fragility of the hybrid gel. Potassium chloride was used to adjust the electrical conductivity of the gel to a range of 5-130 MHz, so that it would be equivalent to that of muscle tissue for each frequency used by electromagnetic heating devices. N-butanol was used to adjust the clouding temperature to a range between 45 and 55 degrees C. In the present study we clarified the important properties of the new phantom, and developed formulae for easy determination of the amounts of ingredients necessary for the desired clouding temperature and electric conductivity. The characteristics of this phantom are: a) a solid form to avoid convection by heat conduction; b) sufficient strength without fragility to form a torso without the use of a reinforcing agent; c) high transparency at room temperature and visualization of the heating area as a white turbidity; d) time-lapse and accurate visualization of the changing temperature area without thermal hysteresis; e) electrical properties similar to those of human tissues; f) ease of production; and g) low cost and good safety. This phantom might assist oncologists in their routine checking and study of the performance of electromagnetic heating devices for hyperthermia and radiofrequency ablation.

Biochemical comparison between radon effects and thermal effects on humans in radon hot spring therapy.

The radioactive and thermal effects of radon hot spring were biochemically compared under a sauna room or hot spring conditions with a similar chemical component, using the parameters that are closely involved in the clinic for radon therapy. The results showed that the radon and thermal therapy enhanced the antioxidation functions, such as the activities of superoxide dismutase (SOD) and catalase, which inhibit lipid peroxidation and total cholesterol produced in the body. Moreover the therapy enhanced concanavalin A (ConA)-induced mitogen response and increased the percentage of CD4 positive cells, which is the marker of helper T cells, and decreased the percentage of CD8 positive cells, which is the common marker of killer T cells and suppressor T cells, in the white blood cell differentiation antigen (CD8/CD4) assay. Furthermore, the therapy increased the levels of alpha atrial natriuretic polypeptide (alpha ANP), beta endorphin, adrenocorticotropic hormone (ACTH), insulin and glucose-6-phosphate dehydrogenase (G-6-PDH), and it decreased the vasopression level. The results were on the whole larger in the radon group than in the thermal group. The findings suggest that radon therapy contributes more to the prevention of life-style-related diseases related to peroxidation reactions and immune suppression than to thermal therapy. Moreover, these indicate what may be a part of the mechanism for the alleviation of hypertension, osteoarthritis (pain), and diabetes mellitus brought about more by radon therapy than by thermal therapy.

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. GdCl(3) was added as a T(1) modifier and agarose as a T(2) 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 T(1) value of 202-1904 ms and a T(2) value of 38-423 ms when the GdCl(3) concentration was varied from 0-140 mumol/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 T(1) and T(2) values and which is capable of retaining its shape.

Adenoviral p53 gene therapy in head and neck squamous cell carcinoma cell lines.

We reconstructed the recombinant p53-expressing adenovirus and examined its infections and effects in head and neck squamous cell carcinoma cell lines. Eight human head and neck squamous cell carcinoma cell lines were infected by the recombinant adenovirus harboring the lacZ gene (AxCAiLacZ) or the wild-type p53 gene (AxCAip53), and the effects were investigated. The eight cell lines were successfully infected by AxCAiLacZ at a level of more than 50%. The survival of all 8 squamous cell lines were inhibited in the range from 8 to 26.7% by only one treatment of the AxCAip53 infection. This result suggested that p53 gene therapy might become a useful tool in head and neck squamous cell carcinoma treatment.

Thermoradiotherapy in human head and neck squamous cell carcinoma cell lines.

Thermoradiosensitivity of 8 cell lines of head and neck squamous cell carcinoma (HO-1-u-1, HSC2, HSC3, HSC4, SAS, KB, Hep2, and Ca9-22) was investigated. The differences of radiosensitivity between the cell line with the highest radiosensitivity and the cell line with the lowest radiosensitivity were 1.7-, 7.7-, and 41-fold at 2, 6 and 8 Gy, respectively. The differences between the cell line with the highest thermosensitivity and the cell line with the lowest thermosensitivity were 2.4-, 6.2- and 34.4-fold at 43 degrees C for 40, 60 and 100 min, and 2.6-, 4.9- and 127-fold at 44 degrees C for 20, 30 and 50 min, respectively. These findings indicated that there were large differences in both radiosensitivity and thermosensitivity among the 8 cell lines. There was a negative relationship between radiosensitivity and thermosensitivity (43 degrees C: r=-0.600, 44 degrees C: r=-0.848) in 7 of 8 cell lines, the exception being the HSC4 cell line, which was resistant to both therapies. Four of the 8 cell lines at 43 degrees C and 5 at 44 degrees C in the radiotherapy combined with thermotherapy showed actual survival rates smaller than the theoretical survival rates. Thus, thermoradiotherapy was deemed effective in the head and neck carcinoma cell lines, although 1 of 8 cell lines was resistant to both radiotherapy and thermotherapy.

Thermochemotherapy of a human salivary adenocarcinoma cell line.

We report on thermochemotherapy in a human salivary gland adenocarcinoma cell line. Hyperthermia reduced the survival rate to 50 and 20% by heating at 43 degrees C for 40 and 60 min, respectively, and is by itself useful in human salivary gland carcinoma treatment. Adriamycin, cisplatin, and mitomycin C can possible be used clinically, while bleomycin and 5-fluorouracil cannot, to treat this carcinoma. The optimal temperature was considered to be 41 degrees C in adriamycin, 42 degrees C in cisplatin, 37 degrees C in mitomycin C, and 42 degrees C in bleomycin in the thermochemotherapy. Thermochemotherapy is a useful tool in the treatment of human salivary gland carcinoma cells, but it is necessary to select the best anticancer drugs and the optimal temperature for optimal success using this treatment.

Effect of wortmannin on the suppression of thermotolerance in tsAF8 cells.

Phosphatidylinositol 3 kinases (PI-3 kinases) play a crucial role in the inositol phospholipid signaling pathway. The effect of wortmannin, an inhibitor of PI-3 kinases, on the suppression of thermotolerance development was investigated in the temperature-sensitive cell line tsAF8. When wortmannin was added immediately after the preheating, the thermotolerance was suppressed, with this suppression being dose-dependent from 0.01 to 0.1 microM, but not dose-dependent from 0.1 to 20 microM. Our results suggest that PI-3 kinases might play an important role in thermotolerance development in tsAF8 cells.