Applicability Evaluation of Full-Reference Image Quality Assessment Methods for Computed Tomography Images.

Image quality assessments (IQA) are an important task for providing appropriate medical care. Full-reference IQA (FR-IQA) methods, such as peak signal-to-noise ratio (PSNR) and structural similarity (SSIM), are often used to evaluate imaging conditions, reconstruction conditions, and image processing algorithms, including noise reduction and super-resolution technology. However, these IQA methods may be inapplicable for medical images because they were designed for natural images. Therefore, this study aimed to investigate the correlation between objective assessment by some FR-IQA methods and human subjective assessment for computed tomography (CT) images. For evaluation, 210 distorted images were created from six original images using two types of degradation: noise and blur. We employed nine widely used FR-IQA methods for natural images: PSNR, SSIM, feature similarity (FSIM), information fidelity criterion (IFC), visual information fidelity (VIF), noise quality measure (NQM), visual signal-to-noise ratio (VSNR), multi-scale SSIM (MSSSIM), and information content-weighted SSIM (IWSSIM). Six observers performed subjective assessments using the double stimulus continuous quality scale (DSCQS) method. The performance of IQA methods was quantified using Pearson's linear correlation coefficient (PLCC), Spearman rank order correlation coefficient (SROCC), and root-mean-square error (RMSE). Nine FR-IQA methods developed for natural images were all strongly correlated with the subjective assessment (PLCC and SROCC > 0.8), indicating that these methods can apply to CT images. Particularly, VIF had the best values for all three items, PLCC, SROCC, and RMSE. These results suggest that VIF provides the most accurate alternative measure to subjective assessments for CT images.

Standardization of Breast Dynamic Contrast-enhanced MRI Signal with Application to the Assessment of Background Parenchymal Enhancement Rate.

BACKGROUND: There is currently no clinically accepted method for quantifying background parenchymal enhancement (BPE), though a sensitive method might allow individualized risk management based on the response to cancer-preventative hormonal therapy. OBJECTIVE: The objective of this pilot study is to demonstrate the utility of linear modeling of standardized dynamic contrast-enhanced MRI (DCEMRI) signal for quantifying changes in BPE rates. METHODS: On a retrospective database search, 14 women with DCEMRI examinations pre- and post- treatment with tamoxifen were identified. DCEMRI signal was averaged over the parenchymal ROIs to obtain time-dependent signal curves S(t). The gradient echo signal equation was used to standardize scale S(t) to values of (FA) ̃ = 10° and (TR) ̃ = 5.5 ms, and obtain the standardized parameters of DCE-MRI signal S ̃_p (t). Relative signal enhancement (〖RSE〗_p ) ̃ was calculated from S ̃_p, and the reference tissue method for T1 calculation was used to standardize (〖RSE〗_p ) ̃ to gadodiamide as the contrast agent, obtaining (RSE) ̃. (RSE) ̃, in the first 6 minutes, post-contrast administration was fit to a linear model with the slope α ̃_RSE denoting the standardized rate relative BPE. RESULTS: Changes in α ̃_RSE were not found to be significantly correlated with the average duration of tamoxifen treatment, age at the initiation of preventative treatment, or pre-treatment BIRADS breast density category. The average change in α ̃_RSE showed a large effect size of -1.12, significantly higher than -0.86 observed without signal standardization (p < 0.01). CONCLUSION: Linear modeling of BPE in standardized DCEMRI can provide quantitative measurements of BPE rates, improving sensitivity to changes due to tamoxifen treatment.

Diagnostic value of electric properties tomography (EPT) for differentiating benign from malignant breast lesions: comparison with standard dynamic contrast-enhanced MRI.

OBJECTIVES: To evaluate the diagnostic utility of electric properties tomography (EPT) in differentiating benign from malignant breast lesions in comparison with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: In this institutional review board-approved retrospective study, 116 consecutive patients with 141 breast lesions (50 benign and 91 malignant) underwent 3-T MRI, including 3D turbo-spin echo (TSE) sequence and standard DCE-MRI scans between January 2014 and January 2017. The lesions were segmented semi-automatically using subtraction DCE-MR images, and they were registered to the phase images from 3D TSE. The mean conductivity of the lesion was obtained from phase-based reconstruction of lesions. From the DCE-MRI, initial enhancement rate (IER) and signal enhancement ratio (SER) were calculated from signal intensity (SI) as follows: IER = (SIearly - SIpre)/SIpre, SER = (SIearly - SIpre)/(SIdelayed - SIpre). The parameters from EPT and the DCE-MRI were compared between benign and malignant lesions. RESULTS: There was significant difference in mean conductivity (0.14 ± 1.77 vs 1.14 ± 1.36 S/m, p < 0.0001) and SER (0.77 ± 0.28 vs 1.04 ± 0.25, p < 0.0001) between benign and malignant lesions, but not in IER (p = 0.06). Receiver operating curve (ROC) analysis revealed that the area under the curve (AUC) of the mean conductivity and SER was 0.71 and 0.80, respectively, without significant difference (p = 0.15). CONCLUSIONS: The mean conductivity of EPT was significantly different between benign and malignant breast lesions as well as kinetic parameter or SER from DCE-MRI. KEY POINTS: • The conductivity of malignant lesions was higher than that of benign lesions. • EPT helps differentiatie benign from malignant lesions. • Diagnostic ability of EPT was not significantly different from that of DCE-MRI.

Fast Temporal Resolution Dynamic Contrast-Enhanced MRI: Histogram Analysis Versus Visual Analysis for Differentiating Benign and Malignant Breast Lesions.

OBJECTIVE: The purpose of this study was to validate a kinetic assessment based on visually identified peak enhancement, which is routinely used in clinical practice, for differentiating benign from malignant lesions during fast dynamic contrast-enhanced MRI. MATERIALS AND METHODS: Between January 2015 and December 2016, 90 consecutively registered patients with 105 breast lesions (40 benign, 65 malignant) underwent dynamic contrast-enhanced 1.5-T MRI that included one unenhanced and eight contrast-enhanced fast temporal resolution (10 seconds) whole-breast acquisitions. Histogram analysis was performed to measure the voxel-based enhancement of the entire lesion to obtain 90th, 75th, and 50th percentile values at each time point and to generate kinetic curves. Two observers selected visually identified peak enhancement within the lesions to generate the kinetic curves. The kinetic curves from histogram and visually identified peak enhancement analyses were fitted by means of an empiric mathematic model (EMM): ΔS(t) = A × (1 - e-αt), where A is the upper limit of signal intensity, e indicates the exponential function, and α (min-1) is the rate of increase in signal intensity. The initial slope of the kinetic curve (A × α) and the initial AUC (AUC30) were calculated. These parameters were compared between benign and malignant lesions, and results from visually identified peak enhancement analysis were compared with those from histogram analysis. RESULTS: Benign lesions were successfully differentiated from malignant lesions in both visually identified peak enhancement and histogram analyses (90th and 75th percentile values) on the basis of α, A × α, and AUC30 from the EMM. There was no significant difference in ROC AUC in these EMM parameters between visually identified peak enhancement and histogram analyses (p = 0.21). CONCLUSION: Kinetic assessment with visually identified peak enhancement was acceptable for differentiating benign from malignant lesions.

Analysing voice quality and pitch in interactions of emergency care simulation.

Background/aims: In emergency care, healthcare professionals (HCPs) interact with both a patient and their colleagues at the same time. How HCPs regulate the two distinct interactions is our central interest. Focusing on HCPs' use of their voice quality and pitch, a multimodal analysis of the interaction in a simulation training session was conducted. Our aims are (1) to compare the use of HCPs' voice quality and pitch in HCP-patient and HCP-HCP interactions, (2) to examine how different voice quality and pitch function in interaction, and (3) to develop the research methodology so as to integrate multimodal features in emergency care interaction for analysis. Methods: Three HCPs performed a scripted acute care scenario (chest pain) at the simulation centre. The multimodal corpus-based approach was applied to analyse the varying voice pitch and quality of the HCPs, in interactions with a simulated patient (SP) and with two other HCPs, in emergency care training. Results: The HCPs tended to use a clear voice when they talk to an SP and a 'shattered' voice to colleagues in the team. The pitch was raised to talk to an SP, by Helen (a nurse) and Mike (a doctor). Conclusion: This indicates that the HCPs strategically change their voice quality and pitch according to the addressees, regulating the interaction.

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.

Value of breast MRI for patients with a biopsy showing atypical ductal hyperplasia (ADH).

PURPOSE: To evaluate the diagnostic value of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for patients with atypical ductal hyperplasia (ADH) in predicting malignant upgrade. MATERIALS AND METHODS: 3T DCE-MRI was performed for 17 patients with ADH (median age 52, range 42-76) proven by stereotactic biopsy (n = 15), and ultrasound-guided biopsy (n = 2) from January 2011 to April 2015. All patients underwent surgical excision after the MRI. Two radiologists prospectively reviewed the MRI to determine the presence or absence of suspicious findings at the site of biopsy, and evaluated the MR features of any lesion present according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon. MRI findings and clinical information were correlated with the final surgical pathology by multivariate analysis. RESULTS: Nine of 17 lesions were upgraded to malignancy. MRI demonstrated suspicious nonmass enhancement (NME) at the site of biopsy in all upgraded patients. The median size was 19.5 mm (range, 9-44 mm). In the eight patients without upgrade, no enhancement (n = 2), linear enhancement along the biopsy track (n = 4), thin rim enhancement around hematoma (n = 1), and a focal NME (n = 1) were seen. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI findings were 100, 87.5, 90, and 100%, respectively. Multivariate analysis revealed that the presence of suspicious enhancement on MRI was the most significant predictor of upgrade to malignancy (P = 0.0006) CONCLUSION: Our study revealed a high NPV of DCE-MRI for patients with ADH in terms of malignant upgrade at subsequent surgery. This suggests that patients with ADH without suspicious enhancement on DCE-MRI might be followed with DCE-MRI rather than undergoing surgical excision. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1738-1747.

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.

Kinetic Analysis of Benign and Malignant Breast Lesions With Ultrafast Dynamic Contrast-Enhanced MRI: Comparison With Standard Kinetic Assessment.

OBJECTIVE: The purposes of this study were to evaluate diagnostic parameters measured with ultrafast MRI acquisition and with standard acquisition and to compare diagnostic utility for differentiating benign from malignant lesions. MATERIALS AND METHODS: Ultrafast acquisition is a high-temporal-resolution (7 seconds) imaging technique for obtaining 3D whole-breast images. The dynamic contrast-enhanced 3-T MRI protocol consists of an unenhanced standard and an ultrafast acquisition that includes eight contrast-enhanced ultrafast images and four standard images. Retrospective assessment was performed for 60 patients with 33 malignant and 29 benign lesions. A computer-aided detection system was used to obtain initial enhancement rate and signal enhancement ratio (SER) by means of identification of a voxel showing the highest signal intensity in the first phase of standard imaging. From the same voxel, the enhancement rate at each time point of the ultrafast acquisition and the AUC of the kinetic curve from zero to each time point of ultrafast imaging were obtained. RESULTS: There was a statistically significant difference between benign and malignant lesions in enhancement rate and kinetic AUC for ultrafast imaging and also in initial enhancement rate and SER for standard imaging. ROC analysis showed no significant differences between enhancement rate in ultrafast imaging and SER or initial enhancement rate in standard imaging. CONCLUSION: Ultrafast imaging is useful for discriminating benign from malignant lesions. The differential utility of ultrafast imaging is comparable to that of standard kinetic assessment in a shorter study time.

Simulated patients versus manikins in acute-care scenarios.

BACKGROUND: Manikins and simulated patients (SPs) are commonly used in health care education and assessment. SPs appear to offer a more realistic experience for learners than 'plastic' manikins, and might be expected to engender interactions that approximate real clinical practice more closely. The analyses of linguistic patterns and touch are methodologies that could be used to explore this hypothesis. Our research aims were: (1) to compare verbal interactions and the use of procedural touch by health care workers (HCWs) in scenarios with SPs and with manikins; and (2) to evaluate the methodologies used to inform a large-scale study. METHODS: We conducted a pilot preliminary comparative study on conversations and touch in two scenarios in emergency care training, each performed using an SP and a high-fidelity manikin. The setting was a simulation centre. Two scripted acute-care scenarios (chest pain and acute breathlessness) were performed using both an SP and a high-fidelity manikin. Audiovisual recordings were subsequently analysed. Two teams comprising a clinician (medical student), a senior nurse and a clinical support worker took part in the study. The linguistics research methodology integrated a multimodal corpus-based approach and discourse analysis. Simulated patients appear to offer a more realistic experience for learners than 'plastic' manikins RESULTS: Overall, HCWs had far more interactions with the SPs than with the manikins, and the utterances and behaviours were more akin to what one would expect in real clinical practice. HCWs used procedural touch without the patient's permission much more frequently with the manikin. DISCUSSION: These methodologies offer opportunities for further research projects studying interactions with SPs, manikins and real clinical practice.

Asialoerythropoietin ameliorates bleomycin-induced acute lung injury in rabbits by reducing inflammation.

Acute lung injury, a critical illness characterized by acute respiratory failure with bilateral pulmonary infiltrates, remains unresponsive to current treatments. The condition involves injury to the alveolar capillary barrier, neutrophil accumulation and the induction of proinflammatory cytokines followed by lung fibrosis. In the present study, a rabbit model of bleomycin-induced acute lung injury was established to examine the effects of asialoerythropoietin (AEP), an agent with tissue-protective activities, on pulmonary inflammation. Six Japanese white rabbits were randomly divided into two equal groups. Acute lung injury was induced in all rabbits by intratracheally injecting bleomycin. The control group was injected with bleomycin only; the experimental (AEP) group was injected intravenously with AEP (80 µg/kg) prior to the bleomycin injection. Computed tomography (CT) studies were performed seven days later. The CT inflammatory scores of areas exhibiting abnormal density and the pathological inflammatory scores were recorded as a ratio on a 7×7 mm grid. The CT and pathological inflammatory scores were significantly different between the control and AEP groups [122±10 and 16.3±1.5 (controls) vs. 71±8.5 and 9.7±1.4 (AEP), respectively; P<0.01]. Thus, the present study revealed that AEP prevents bleomycin-induced acute lung injury in rabbits.

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.

Atherosclerotic imaging using 4 types of superparamagnetic iron oxides: new possibilities for mannan-coated particles.

PURPOSE: We used magnetic resonance imaging (MRI) and histologic techniques to compare the uptake by the rabbit atherosclerotic wall of 4 types of superparamagnetic iron oxide (SPIO) particles, i.e. SPIO, mannan-coated SPIO (M-SPIO), ultrasmall SPIO (USPIO), and mannan-coated USPIO (M-USPIO). MATERIALS AND METHODS: All experimental protocols were approved by our institutional animal experimentation committee. We intravenously injected 12 Watanabe heritable hyperlipidemic rabbits with one of the 4 types of SPIO (0.8 mmol Fe/kg). Two other rabbits served as the control. The rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before- and 5 days after these injections; excised aortae were subjected to in vitro MRI. In the in vivo and in vitro studies we assessed the signal intensity of the vessels at identical regions of interest (ROI) and calculated the signal-to-noise ratio (SNR). For histologic assessment we evaluated the iron-positive regions in Prussian blue-stained specimens. RESULTS: There were significant differences in iron-positive regions where M-USPIO>USPIO, M-SPIO>SPIO, USPIO>SPIO (p<0.05) but not between M-USPIO and M-SPIO. The difference between the pre- and post-injection SNR was significantly greater in rabbits treated with M-USPIO than USPIO and in rabbits injected with M-SPIO than SPIO (p<0.05). On in vitro MRI scans SNR tended to be lower in M-USPIO- and M-SPIO- than USPIO- and SPIO-treated rabbits (p<0.1). CONCLUSION: Histologic and imaging analysis showed that mannan-coated SPIO and USPIO particles were taken up more readily by the atherosclerotic rabbit wall than uncoated SPIO and USPIO.

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.

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.

Negatively charged superparamagnetic iron oxide nanoparticles: a new blood-pooling magnetic resonance contrast agent.

PURPOSE: Our purpose was to investigate the utility of superparamagnetic iron-oxide nanoparticles (SPIO) as a blood-pooling contrast agent at magnetic resonance imaging (MRI). MATERIALS AND METHODS: We studied four contrast agents: carboxymethyl-diethylaminoethyl dextran magnetite SPIO (CMEADM-S, diameter 54 nm), negatively charged CMEADM ultrasmall SPIO (CMEADM-U, 32 nm), alkali-treated dextran magnetite SPIO (ATDM-S, 55 nm), and ATDM ultrasmall SPIO (ATDM-U, 28 nm) carrying a neutral charge. Each contrast agent (80 µmol/kg) was injected intraperitoneally into apolipoprotein E (apoE) mice and the tissue iron concentration was measured 30-, 60-, 180-, and 300-min later by nuclear MR. For MR angiographic (MRA) evaluation, we injected the agents into the auricular vein of four groups of 15 rabbits. Immediately and 30-, 60-, 180-, and 300-min later, three rabbits from each group were subjected to MRI. The organ/background signal ratio (SR) was calculated. Statistical analyses were performed with Tukey's honestly significant difference (HSD) test. RESULTS: At 60 and 180 min, blood-iron concentration of CMEADM-U was significantly different from other contrast agents. In the abdominal aorta and inferior vena cava, SR of CMEADM-U was higher at 180 and 300 min than of the other contrast agents. In the thoracic aorta, there was no difference in SR at 300 min between CMEADM-U and CMEADM-S. CONCLUSION: Negatively charged SPIO nanoparticles may be useful as a blood-pooling contrast agent.