Increased 18F-FDG accumulation in less-affected lung area in patients with non-small cell lung cancer and postoperative acute exacerbation of interstitial lung disease.

PURPOSE: To investigate whether or not 18F-FDG accumulation in normal or less-affected lung fields increased in non-small cell lung cancer (NSCLC) patients with postoperative acute exacerbation (PAE) of interstitial lung disease (ILD) MATERIAL AND METHODS: Thirty-six NSCLC patients with ILD and 50 patients without ILD (non-ILD patients) underwent pre-operative 18F-FDG-PET/CT at 2 institutions. Volume-of-interest (VOI) was placed to measure the mean standardized uptake value (SUVmean) in normal or less-affected lung fields at pre-defined 12 areas on ventral and dorsal locations of both lungs. SUVtissue fraction (TF) was defined as corrected SUVmean by using TF and mean computed tomography density on PET/CT. Harmonized SUVmean (hSUVmean) and SUVTF (hSUVTF) were calculated based on results of phantom study, which was performed to optimize the measured SUV difference among 2 institutions. Both the h-SUVmean and the h-SUVTF were compared between 8 patients with PAE of ILD (PAE group) or remaining 28 patients without PAE of ILD (non-PAE group) and non-ILD patients in each of the 12 areas. RESULTS: The hSUVmean in PAE group was higher in 9 out of 12 locations as compared with non-ILD patients, whereas the hSUVmean was mostly similar between non-PAE group and non-ILD patients. In contrast, the hSUVTF in non-PAE group was similar to that in PAE group, and higher than in non-ILD patients in most locations. CONCLUSION: 18F-FDG-PET/CT demonstrated increased SUVmean along with elevated SUVTF in normal or less-affected lung fields for NSCLC patients with PAE of ILD, which may reflect regional invisible fibrosis and inflammatory change.

Anti-tumor Effects of Sorafenib Administered at Different Time Points in Combination with Transarterial Embolization in a Rabbit VX2 Liver Tumor Model.

OBJECTIVE: To investigate the most suitable timing parameters when using sorafenib to enhance the anti-tumor effects of transarterial embolization (TAE) in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: Twenty-five Japanese white rabbits were randomly assigned to five equal groups two weeks after VX2 tumor transplantation to the liver. We then performed the combination treatment with sorafenib and TAE in the according ways; Group 1 (TAE just before consecutive 7-day administration of sorafenib), Group 2 (TAE on second day of the administration period), Group 3 (TAE on fourth day of the administration period), and Group 4 (TAE after the administration period). Group 5 underwent TAE only. The anti-tumor effects were assessed by the tumor growth rates and by the immunohistochemical analysis of the density of intratumoral vessels. RESULTS: The tumor size increased by 103 ± 23% in Group 1, 126 ± 50% in Group 2, 177 ± 44% in Group 3 196 ± 78% in Group 4, and 211 ± 20% in Group 5. The difference between Group 1 and Group 5 and Group 2 and Group 5 was significant. The ratio of areas positive for CD31 in specimens was 2.06 ± 0.90% in Group 1, 1.86 ± 0.59% in Group 2, 3.51 ± 2.10% in Group 3, 3.67 ± 0.79% in Group 4, and 4.84 ± 0.81% in Group 5. The difference between Group 1 and Group 5, Group 2 and Group 5, and Group 2 and Group 4 was significant. CONCLUSION: We suggest that the ideal time of TAE is prior to or early after commencement of sorafenib administration.

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.

A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite.

Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd­based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. The present study evaluated whether the degree of charge alters the blood­pooling time. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADM­, CMEADM2­, CMEADM+ (surface charges: ­10.4, ­41.0 and +9.6 mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO; ­11.5 mV). The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel = (SI post­contrast ­ SI pre­contrast / SI pre­contrast) x 100. Following injection with the CMEADMs, but not with USPIO, the in vivo pooling time was prolonged to >300 min. No significant differences were attributable to the electric charge among the CMEADM­, CMEADM2­ or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Taken together, all three differently­charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.

Inhibition of fibrosis and inflammation by triple therapy with pirfenidone, edaravone and erythropoietin in rabbits with drug-induced lung injury: comparison of CT imaging and pathological findings.

In a rabbit model of bleomycin-induced lung injury, computed tomography (CT) and pathological studies were conducted to investigate whether the progression of this injury is inhibited by pirfenidone and by triple therapy with pirfenidone, edaravone and erythropoietin. We divided nine rabbits with bleomycin-induced lung injury into three equally sized groups. Group 1 served as the control, group 2 received pirfenidone alone and group 3 was treated with pirfenidone, edaravone and erythropoietin. Multidetector CT (MDCT) scans were acquired immediately after the administration of bleomycin, and further scans were performed on days 14 and 28. The area of abnormal opacity was calculated. The rabbit lungs were removed and the size of abnormal areas in macroscopic specimens was calculated and the degree of fibrosis and inflammation in microscopic specimens was scored. In order, the average size of the area of abnormal opacity on CT scans was largest in group 1, followed by groups 2 and 3. On day 28, the area of opacity was significantly smaller in group 3 than in group 1 (P=0.071). The average size of the area of abnormal opacity on macroscopic findings was largest in group 1, followed in order by groups 2 and 3; the difference between group 1 and 3 was significant (P<0.05). The average fibrosis score was highest in group 3 followed by groups 2 and 1. By contrast, the average inflammation score was highest in group 2 followed by groups 1 and 3. Although the administration of pirfenidone alone slowed the progression of bleomycin-induced lung injury, the triple-drug combination was more effective.

Antitumor effect of miriplatin-lipiodol suspension/emulsion using a VX2 liver tumor model.

OBJECTIVE: To evaluate the antitumor effects of miriplatin-lipidol suspension and emulsion. MATERIALS AND METHODS: Fifty rabbits with VX2 liver tumors were randomly assigned to ten groups. Then, we prepared four types of mixtures: a suspension of lipiodol and miriplatin (ML), an emulsion of miriplatin dissolved with lipiodol and contrast medium (MLC) or saline (MLS), and saline alone (S). Ratios between lipiodol and contrast medium/saline volumes were 1:1/4, 1:1/2, 1:1, and 1:2 respectively. We used the same dose of miriplatin (2 mg/kg) and lipiodol (0.1 ml/kg) in each emulsion and suspension group. After intra-arterial infusion, the tumor growth rate was calculated, and sequential change of the plasma platinum concentration, the platinum concentration in the tumor and in surrounding normal liver tissue was also measured. RESULTS: Among the ten groups, the tumor growth rate was lower in MLC and MLS groups, and the difference between tumor treated with MLS emulsion (ratio 1:1/2) and ML suspension was significant (p = 0.02). The platinum concentration in the normal liver tissue was lower in MLS and MLC groups than in the ML group, and that in the tumor was higher in the MLS and MLC emulsion (ratio 1:1/2) groups. CONCLUSION: We suggest that miriplatin-lipiodol emulsion may be more effective than suspension.

Evaluation of the embolic effect and degradability of gelatin microspheres and Gelpart particles.

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.

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

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. Cramer's 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.

Gelatin microspheres: correlation between embolic effect/degradability and cross-linkage/particle size.

PURPOSE: To evaluate the embolic effect and degradability of gelatin microspheres (GMS) using various degrees of cross-linkage and particle sizes in rabbit renal artery embolization. METHODS: Four types of GMS were used, as follows: 2 types of cross-linkage and 2 types of particle size. Twenty-four rabbits (6 in each group) were used for the renal artery embolization. Renal angiography was performed before and after embolization of right renal artery. Follow-up renal angiography was performed 2 days (n = 2), 5 days (n = 2), and 15 days (n = 2) after embolization in each group, and then kidneys were removed for histopathological evaluation. Vascular areas of the angiography were measured by Image J software, and the reperfusion rate was calculated. In renal specimens, residual GMS were checked and the degree of degradation was classified according to a 4-point scale. RESULTS: The mean amounts of large- and small-particle-size GMS injected were 15.0 and 34.3 mg, respectively. Tissue necrosis was confirmed in each group; however, no difference was observed among groups. Renal reperfusion was observed more with small GMS than with large GMS. Renal reperfusion was also observed more with low cross-linked GMS than with high cross-linked GMS. In histopathological specimens, large GMS were confirmed in lobar artery, and small GMS were confirmed in lobular artery. Low cross-linked GMS completely degraded 15 days after embolization. In contrast, high cross-linked GMS were persistent 15 days after embolization. CONCLUSION: Degree of cross-linkage and particle size affected degradability and reperfusion.

Vascular regeneration by pinpoint delivery of growth factors using a microcatheter reservoir system in a rabbit hind-limb ischemia model.

The purpose of this study was to compare the results of delivering low doses of growth factor iteratively (20 µg x5) via a reservoir system with results obtained following a single administration of 100 µg of growth factor. The delivery systems using gelatin microspheres (GMS) facilitate the controlled release of drugs. The controlled release of growth factors at specific sites is essential for vascular regeneration. An ischemic hind-limb model was established in nine rabbits. A reservoir system was implanted in each rabbit. GMS impregnated with basic fibroblast growth factor (bFGF) through an indwelling 2-Fr catheter was infused in the reservoir system. The rabbits were divided into three equal groups: group 1 received 20 µg iteratively (x5) via the reservoir, a single dose of 100 µg growth factor was administered to group 2 and group 3 was the saline control. The therapeutic effects were evaluated by measuring the thigh temperature, blood pressure and blood flow. An immunohistological analysis was also performed for CD31. No significant difference was observed between preand post-treatment (4 weeks following bFGF infusion) in the thigh temperature, blood pressure and blood flow results from each group. Pathological analysis revealed that the number of regenerated vessels was significantly higher in the group treated iteratively with low-dose bFGF.

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.

Comparison of the anti-tumor effects of two platinum agents (miriplatin and fine-powder cisplatin).

PURPOSE: This study was designed to evaluate the anti-tumor effects of miriplatin-lipidol and fine-powder cisplatin-lipiodol suspensions. METHODS: Assessment of the cytotoxicity of two drugs was performed: a soluble derivative of miriplatin (DPC) and fine-powder cisplatin. We randomly divided 15 rabbits with transplanted VX2 liver tumors into three equal groups. They were infused via the proper hepatic artery with a miriplatin-lipiodol suspension (ML), a fine-powder cisplatin-lipiodol suspension (CL), or saline (control) and the tumor growth rate was determined on MR images acquired before and 7 days after treatment. The concentration of platinum (PCs) in blood was assayed immediately, and 10, 30, and 60 min, and 24 h and 7 days after drug administration. Its concentration in tumor and surrounding normal liver tissues was determined at 7 days postadministration. RESULTS: At high concentrations, fine-powder cisplatin exhibited stronger cytotoxicity than DPC. At low concentrations, both agents manifested weak cytotoxicity. While there was no difference between the tumor growth rate of the ML and the CL groups, the difference between the controls and ML- and CL-treated rabbits was significant. The blood PCs peaked at 10 min and then gradually decreased over time. On the other hand, no platinum was detected at any point after the administration of ML. There was no difference between the ML and CL groups in the PCs in tumor tissues; however, in normal hepatic tissue, the PCs were higher in ML- than CL-treated rabbits. CONCLUSIONS: We confirmed the anti-tumor effect of ML and CL. There was no significant difference between the anti-tumor effect of ML and CL at 7 days postadministration.

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.

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.

Enhanced antitumor effect of tirapazamine delivered intraperitoneally to VX2 liver tumor-bearing rabbits subjected to transarterial hepatic embolization.

PURPOSE: We evaluated the effects of the combination of Tirapazamine (TPZ), activated preferentially under hypoxic conditions, and gelatin microspheres (GMS) on the tumor growth ratio in rabbits. METHODS: We assigned 20 liver tumor-bearing Japanese white rabbits to 4 equal groups. Group 1 received 1 ml of saline intra-arterially (i.a.) and 20 ml of saline intraperitoneally (i.p.; saline group). Group 2 was injected with GMS i.a. and 20 ml saline i.p. (GMS group). Group 3 received 1 ml of saline i.a. and 300 mg/m(2) of TPZ i.p. (TPZ group), and group 4 was treated with GMS i.a. and 300 mg/m(2) of TPZ i.p. (GMS + TPZ group). The infusion of GMS was stopped when the blood flow stagnated. Before and 7 days after treatment, the liver tumor volumes were measured as the total number of pixels on 0.3Tesla (T) magnetic resonance imaging (MRI) scans. RESULTS: The tumor growth ratio (mean ± standard deviation) of the saline, GMS, TPZ, and GMS + TPZ groups was 519.15 ± 93.78, 279.24 ± 91.83, 369.78 ± 95.73, and 119.87 ± 17.62, respectively. The difference between the GMS + TPZ group and the other groups was statistically significant (P < 0.05). CONCLUSIONS: Our results show that the combination of TPZ i.p. and GMS i.a. enhanced the antitumor effect of TPZ. This procedure may represent a new alternative treatment for patients with hepatic cell carcinoma.

Quantitative measurement of bleomycin-induced lung fibrosis in rabbits using sequential in vivo regional analysis and high-resolution computed tomography: correlation with pathologic findings.

RATIONALE AND OBJECTIVES: To examine the feasibility of quantitative high-resolution computed tomography (HRCT) findings to monitor the stage of bleomycin-induced pulmonary fibrosis in rabbits by correlating HRCT and pathologic scores and analyzing sequential changes on HRCT images using regional volume histograms. MATERIALS AND METHODS: Lung fibrosis was induced by injecting bleomycin intratracheally into 23 Japanese white rabbits. Rabbits were randomly separated into seven groups depending on follow-up period (12-hour, 24-hour, 3-day, 7-day, 14-day, 21-day, and 28-day). Four-row HRCT examinations were performed at any of the seven time points in each follow-up period and just after bleomycin administration in addition to pre-bleomycin administration as the baseline scan. Scores of consolidation, homogenous ground-glass opacity (GGO), inhomogeneous GGO, reticulolinear shadow, and honey-comb formation were recorded as ratio of affected area to total cross-section in four transaxial planes. Inflammatory and fibrous changes were scored histopathologically. Correlations between HRCT and pathologic findings were assessed. Sequential changes on HRCT images in areas with pathologically confirmed fibrosis were assessed on volume histograms of cubic regions of interest (ROI) using quantitative parameters. RESULTS: Consolidation and inhomogeneous GGO exhibited fair correlations with inflammation scores (r = 0.273, P = .009, and r = 0.393, P < .001); reticulolinear shadow and inhomogeneous GGO had a fair and good correlation, respectively, with fibrous scores (r = 0.327, P = .001, and r = 0.579, P < .001). Inhomogeneous GGO was hardly detected on regional images at 21 and 28 days after bleomycin administration. As to mean computed tomography attenuation, skewness, and kurtosis, inhomogeneous GGO differed from reticulolinear shadow and consolidation. CONCLUSION: Using appropriate ROI settings, quantitative assessment of inhomogeneous GGO with regional volume histograms enables us to monitor the progression of lung fibrosis by sequential observations.

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.

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

PURPOSE: Using 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 METHODS: The 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. RESULTS: The 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. CONCLUSION: Ultrasonography was able to detect contrast enhancement of the IMC at 10 and 20 min after injection of MB.

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 (µm(2)) 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.

Cisplatin-conjugated porous gelatin particles: assessment of optimal conditions for binding and release.

This study was designed to evaluate the optimal conditions for binding cisplatin and porous gelatin particles (PGPs) and to establish in vivo drug release pharmacokinetics. PGPs were immersed in cisplatin solutions under different conditions: concentration, immersion time, and temperature. Thereafter, PGPs were washed in distilled water to remove uncombined cisplatin and were then freeze-dried. The platinum concentration (PC) in the PGPs was then measured. For the in vivo release test, 50 mg/kg of the cisplatin-conjugated PGPs was implanted subcutaneously in the abdominal region of two rabbits. PCs in the blood were measured at different time intervals. PCs significantly increased in direct proportion to the concentration and immersion time (p < 0.01). Although PC increased at higher solution temperature, it was not a linear progression. For the in vivo release test, platinum was released from cisplatin-conjugated PGPs after 1 day, and the peak PC was confirmed 2 days after implantation. Platinum in the blood was detected until 7 days after implantation in one rabbit and 15 days after administration in the other rabbit. Platinum binding with PGPs increased with a higher concentration of cisplatin solution at a higher temperature over a longer duration of time. Release of cisplatin from cisplatin-conjugated PGPs was confirmed in vivo.