Ayumi Nitta-Seko

Histological study of the biodynamics of iron oxide nanoparticles with different diameters.

The biodynamics of ultrasmall and small superparamagnetic iron oxide (USPIO and SPIO, respectively) particles that were injected intraperitoneally into 36 C57BL/6 mice were investigated chronologically. Their distribution was studied histologically at six time points by measuring iron-positive areas (μm2) in organ sections stained with Prussian blue. The uptake of the differently sized particles was also compared by cultured murine macrophages (J774.1). Iron-positive areas in the liver were significantly larger in the mice injected with USPIO than those injected with SPIO at the first three time points (P < 0.05). The amount of USPIO in the lung parenchyma around the airway was larger than that of SPIO at four time points (P < 0.05); distribution to the lymph nodes was not significantly different. The amount of iron was significantly larger in SPIO- than USPIO-treated cultured cells (P < 0.05). In conclusion, it is suggested that intra peritoneally injected USPIO particles could be used more quickly than SPIO to make Kupffer images of the liver and that both agents could help get lymph node images of similar quality.

Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential.

We developed a dextran-magnetite conjugated cisplatin (DM-Cis) complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron). The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH) device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip) and placed magnets subcutaneously (sc). In group 2 we injected saline (ip) and placed magnets (sc). In group 3 we injected DM-Cis (ip) and placed a sc incision (sham). The control (group 4) received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (μm2) were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 μg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05) in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a magnetically-accumulated anticancer drug with hyperthermic effects.

Time-course studies of implanted rabbit VX2 liver tumors to identify the appropriate time for starting hepatic arterial embolization in animal models.

Purpose: We followed the 4-week course of implanted VX2 tumors in rabbits and compared MRI and pathological findings to determine the appropriate time for starting therapy in animal liver tumor models. Materials and Methods: We used 18 Japanese white rabbits. The VX2 liver tumor was harvested from one tumor-bearing rabbit and implanted in the liver of the other 17 rabbits. They were then sacrificed at 1 (n = 5), 2 (n = 3), 3 (n = 4), and 4 weeks (n = 5) after implantation and MRI study. Using MRI scans and/or pathological specimens of individual rabbits, we evaluated the tumor survival ratio, the major tumor axes, intrahepatic metastases, and peritoneal dissemination. Results: All tumor transplantations were successful. At 1 week, 56.25% of the implanted tumors were visualized on MRI scans. At 2 weeks or later, all transplanted rabbits were confirmed to be tumor-bearing on MRI scans. At 3 weeks after implantation, the tumor size was similar on MRI scans and in pathological specimens. There were no intra-hepatic metastases or peritoneal disseminations within 2 weeks of tumor transplantation. Conclusion: We suggest that in studies of implanted VX2 models addressing the treatment of solid hepatic tumors, it may be prudent to start hepatic arterial embolization at 2 weeks after implantation.

Evaluation of atherosclerotic lesions using dextran- and mannan–dextran-coated USPIO: MRI analysis and pathological findings

Magnetic resonance imaging (MRI) can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO). Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran- and mannan–dextran-coated USPIO (D-USPIO and DM-USPIO, respectively) by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5) or D-USPIO (n = 5). Two rabbits were the controls. The doses delivered were 0.08 (dose 1) (n = 1), 0.4 (dose 2) (n = 1), or 0.8 (dose 3) (n = 3) mmol iron/Kg. The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before and 5 days after USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR) of the aortic wall in the same region of interest (ROI) was calculated in both in vivo and in vitro studies. Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM- rather than D-USPIO (P < 0.05) for all doses. In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-USPIO (P < 0.05). With in vitro MRI scans, SNR was significantly lower in rabbits treated with dose 2 of DM-USPIO compared with D-USPIO treatment (P < 0.05), and it tended to be lower at dose 3 (P < 0.1). In conclusion, we suggest that DM-USPIO is superior to D-USPIO for the study of atherosclerotic lesions in rabbits.

The Possibility of differentiation between nonalcoholic steatohepatitis and fatty liver in rabbits on Gd-EOB-DTPA-enhanced open-type MRI scans.

RATIONALE AND OBJECTIVES We used rabbits to investigate the possibility of differentiating between nonalcoholic steatohepatitis (NASH) and fatty liver (FL) on scans acquired by open-type‒ and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)‒enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS We divided 15 adult rabbits into three equal groups; they received standard (control group), high-fat (FL) content (FL group), or choline-deficient chow (NASH group). With the animals under general anesthesia we acquired scans on an open 0.3-Tesla MRI system. Signal intensity (SI) was measured before and after contrast administration and defined as SI-pre and SI-post, respectively. Relative SI enhancement (Sr) was calculated using the equation: Sr = (average of three SI-post- minus average of three SI values in no-signal fields)/(average of three SI-pre- minus average of three SI values in no-signal fields) × 100. Maximum Sr (Srmax), the time (in seconds) required to reach Srmax (Tmax), and the difference between Srmax and Sr at 30 minutes (Sr(30m)R) were analyzed. RESULTS Srmax was significantly higher in the NASH rabbits than the other two groups (P < .05). CONCLUSIONS In rabbits, the Srmax value made it possible to differentiate NASH from normal and fatty liver.

Evaluation of the embolic effect and degradability of gelatin microspheres and gelpart particles

Abstract Purpose: To evaluate the embolic effect and degradability of gelatin microspheres (GMS) and Gelpart particles (GPS) in dogs subjected to hepatic embolization. Material and methods: We subjected 20 beagles to embolization of the hepatic artery (HA) and assessed the embolic effects of GMS measuring 500 μm in dry and 1 mm in wet state and of 1-mm GPS, porous gelatin embolic particles. We obtained celiac angiographs before and immediately after embolization and two, 14, and 28 days later; the livers were histopathologically evaluated. Reperfusion of HA was assessed by inspecting the arterial branches. We checked the liver specimens for residual GMS, injury to surrounding tissues, and inflammatory changes, and investigated embolic formation in the HA. Results: The mean amount of injected GMS and GPS was 15.5 and 14.5 mg, respectively. While none of the dogs manifested HA reperfusion two days post-embolization, there was angiographic evidence of complete reperfusion 28 days after embolization. In all dogs, histopathological study showed arterial inflammatory changes and injury of surrounding tissues irrespective of the embolization materials used. These findings were pronounced on day 28 in dogs injected with GMS. Conclusion: There was no difference in the embolic effects of GMS and GPS nor in their degradability in dogs subjected to hepatic embolization.

Utility of contrast-enhanced ultrasonography for qualitative imaging of atherosclerosis in Watanabe heritable hyperlipidemic rabbits: initial experimental study

PurposeUsing Watanabe heritable hyperlipidemic (WHHL) rabbits, we investigated the ability of ultrasonography (US) to detect contrast enhancement of atherosclerotic lesions after intravenous injection of a microbubble contrast agent (MB) and confirmed the localization of MB in the lesion by transmission electron microscopy (TEM).Materials and methodsThe abdominal aortic wall of six WHHL rabbits was observed for 20 min after MB delivery. To evaluate contrast enhancement, a region of interest (ROI) was set in the intima-media complex (IMC) and the aortic lumen. The average image brightness of the ROI was recorded as the echogenicity at each time point. Differences at each time point were analyzed by analysis of variance and the t-test. Histological analysis was performed after US observation.ResultsThe echogenicity of the IMC was 8.48 ± 3.01 before and 10.96 ± 7.88, 32.42 ± 12.79, 79, 17.73 ± 9.118, and 31.18 ± 13.35, respectively, at 0.5, 2, 5, 10, and 20 min after MB injection. The echogenicity of the vessel lumen was 1.16 ± 1.57, 64.21 ± 11.52, 53.55 9.81, 13.32 ± 9.78, 2.63 ± 1.45, and 3.66 ± 3.01 at the corresponding time points. At 20 min after injection, the echogenicity of the IMC was significantly higher than before or 0.5 min after injection. The distribution of MB inside macrophages in atherosclerotic plaques could not be confirmed by TEM.ConclusionUltrasonography was able to detect contrast enhancement of the IMC at 10 and 20 min after injection of MB.

A phantom study for ground-glass nodule detectability using chest digital tomosynthesis with iterative reconstruction algorithm by ten observers: association with radiation dose and nodular characteristics

OBJECTIVE To compare detectability of simulated ground-glass nodules (GGNs) on chest digital tomosynthesis (CDT) among 12 images obtained at 6 radiation doses using 2 reconstruction algorithms and to analyze its association with nodular size and density. METHODS 74 simulated GGNs [5, 8 and 10 mm in diameter/-630 and -800 Hounsfield units (HU) in density] were placed in a chest phantom in 14 nodular distribution patterns. 12 sets of coronal images were obtained using CDT at 6 radiation doses: 120 kV-10 mA/20 mA/80 mA/160 mA, 100 kV-80 mA and 80 kV-320 mA with and without iterative reconstruction (IR). 10 radiologists recorded GGN presence and locations by continuously distributed rating. GGN detectability was compared by receiver operating characteristic analysis among 12 images and detection sensitivities (DS) were compared among 12 images in subgroups classified by nodular diameters and densities. RESULTS GGN detectability at 120 kV-160 mA with IR was similar to that at 120 kV-80 mA with IR (0.614 mSv), as area under receiver operating characteristic curve was 0.798 ± 0.024 and 0.788 ± 0.025, respectively, and higher than six images acquired at 120 kV (p < 0.05). For nodules of -630 HU/8 mm, DS at 120 kV-10 mA without IR was 73.5 ± 6.0% and was similar to that by the other 11 data acquisition methods (p = 0.157). For nodules of -800 HU/10 mm, DS both at 120 kV-80 mA and 120 kV-160 mA without IR was improved by IR (56.3 ± 11.9%) (p < 0.05). CONCLUSION CDT demonstrated sufficient detectability for larger more-attenuated GGNs (>8 mm) even in the lowest radiation dose (0.17 mSv) and improved detectability for less-attenuated GGNs with the diameter of 10 mm at submillisievert with IR. Advances in knowledge: IR improved detectability for larger less-attenuated simulated GGNs on CDT.

MRI study of atherosclerotic plaque progression using ultrasmall superparamagnetic iron oxide in Watanabe heritable hyperlipidemic rabbits

OBJECTIVE The purpose of this study was to evaluate plaque progression by using MRI with ultrasmall superparamagnetic iron oxide (USPIO) and by histopathological studies. METHODS We divided 12 Watanabe heritable hyperlipidemic (WHHL) rabbits into 4 groups based on their age (3, 9, 14 and 26 months) and injected them intravenously with 0.8 mmol (Fe) kg(-1) of USPIO (size, 32 nm; concentration, 15 mg dl(-1)). On the fifth post-injection day, they were again given an intravenous injection with 40 μmol kg(-1) of the same USPIO, and MR angiography (MRA) was performed. The signal-to-noise ratio (SNR) in regions of interest in the wall of the upper abdominal aorta was calculated on coronal images. Specimens from the same level of the aorta were subjected to iron staining and RAM-11 immunostaining and used for histopathological study. For statistical analysis of the MRA and histopathological findings, we used analysis of variance [Tukeys honest significant difference (HSD) test]. RESULTS In 9-month-old rabbits, the SNR was significantly lower than in rabbits of the other ages (p < 0.01), and the area of RAM-11 (DAKO Corporation, Glostrup, Denmark) and iron uptake in the aortic wall was significantly larger (RAM-11, p < 0.01; iron, p < 0.05). These areas were the smallest in 3-month-old rabbits. CONCLUSION Histopathologically, the number of macrophages was the greatest in 9-month-old rabbits. Our findings indicate that the SNR on MRI scans reflects the number of macrophages in the aortic wall of WHHL rabbits. ADVANCES IN KNOWLEDGE USPIO-enhanced MRI visualized the accumulation of macrophages in early atherosclerotic plaques of WHHL rabbits in the course of natural progression.

320-detector-row computed tomography arteriography using CO2 gas to detect malignant liver tumors

Abstract Purpose: We present the initial steps for 320-detector-row computed tomography arteriography using CO2 gas (320-MDCT CO2 arteriography) to detect the vascular area of malignant liver tumors. Material and methods: This study was approved by the Ethics Committee of our institution. Written prior informed consent was obtained from all patients. We studied six patients with primary and metastatic liver tumors (n = 26) and allergic reactions to iodinated contrast media or a tendency for renal failure. CO2 was injected at 1 ml/sec (volume 8 ml) into the common hepatic artery and a CT scan was acquired 12 seconds after the start of injection. The detection of the vascular area of the tumor or of intratumor air was evaluated with respect to the relationship between the size and location of the tumors. Cramers V statistic was performed to explore the relationship (p < 0.05). Results: The vascular area was detected in 17 of the 26 tumors (65.4%). There was a correlation between the detection of the adjacent vascular area on CTA images acquired with the use of CO2 and the tumor site observed on previously-acquired MRI or CT images. Conclusion: 320-MDCT CO2 arteriography with microcatheters may be useful for the detection of the vascular area.