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Objective: To explore the gender differences of brain regional homogeneity (ReHo) in healthy subjects during the resting-state, after normal sleep, and after sleep deprivation (SD) using functional magnetic resonance imaging (fMRI) and the ReHo method., Methods: Sixteen healthy subjects (eight males and eight females) each underwent the resting-state fMRI exams twice, i.e., once after normal sleep and again after 24h's SD. According to the gender and sleep, 16 subjects were all measured twice and divided into four groups: the male control group (MC), female control group (FC), male SD group (MSD), and female SD group (FSD). The ReHo method was used to calculate and analyze the data, SPM5 software was used to perform a two-sample T-test and a two-pair T-test with a P value <0.001, and cluster volume ≥ 270 mm(3) was used to determine statistical significance., Results: Compared with the MC, the MSD showed significantly higher ReHo in the right paracentral lobule (BA3/6), but in no obviously lower regions. Compared with the FC, the FSD showed significantly higher ReHo in bilateral parietal lobes (BA2/3), bilateral vision-related regions of occipital lobes (BA17/18/19), right frontal lobe (BA4/6), and lower ReHo in the right frontal lobe. Compared with the FC, the MC showed significantly higher ReHo in the left occipital lobe (BA18/19), and left temporal lobe (BA21), left frontal lobe, and lower ReHo in the right insula and in the left parietal lobe. Compared with the FSD, the MSD showed significantly higher ReHo in the left cerebellum posterior lobe (uvula/declive of vermis), left parietal lobe, and bilateral frontal lobes, and lower ReHo in the right occipital lobe (BA17) and right frontal lobe (BA4)., Conclusions: The differences of brain activity in the resting state can be widely found not only between the control and SD group in a same gender group, but also between the male group and female group. Thus, we should take the gender differences into consideration in future fMRI studies, especially the treatment of brain-related diseases (e.g., depression)., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: To investigate the imaging manifestations of Pneumocystis Jiroveci Pneumonitis (PCP) in AIDS patients, and the correlation between imaging features, CD(4) (+) lymphocyte count, and plasma HIV viral load., Materials and Methods: A total of consecutive 50 AIDS patients with PCP were reviewed retrospectively. Chest CT manifestations, CD(4) (+) lymphocyte count, and plasma HIV viral load were analyzed to investigate their correlation., Results: PCP chest CT manifestations included ground-glass opacities dominated in 28 cases (28/50, 56%), lung cysts dominated in 10 cases (10/50, 20%), consolidation dominated in 6 cases (6/50, 12%), interstitial lesion dominated in 3 cases (3/50, 6%), and mixed lesions in 3 cases (3/50, 6%). In these 50 patients, CD(4) (+) lymphocyte count ranged from 2 to 373 cells/µL. Plasma HIV viral load ranged from 500 to 5.28×10(7) copies/mL. CD(4) (+) lymphocyte count in ground-glass opacities dominated patients was higher than that of lung cyst dominated patients (P<0.05). Plasma virus load of lung cysts dominated PCP patients was higher than that of consolidation dominated patients (P<0.05)., Conclusions: The typical chest imaging features of PCP in AIDS patients included lung ground-glass opacities and lung cysts. The chest imaging features were correlated with CD(4) (+) T lymphocyte count and plasma HIV viral load.

Novel high magnetization microspheres with porous γ-Fe(2)O(3) core and porous SiO(2) shell were synthesized using a templating method, whereas the size of the magnetic core and the thickness of the porous shell can be controlled by tuning the experimental parameters. By way of an example, as-prepared γ-Fe(2)O(3)@meso-SiO(2) microspheres (170 nm) display excellent water-dispersity and show photonic characteristics under externally applied a magnetic field. The magnetic property of the γ-Fe(2)O(3) porous core enables the microspheres to be used as a contrast agent in magnetic resonance imaging with a high r(2) (76.5 s(-1) mM(-1) Fe) relaxivity. The biocompatible composites possess a large BET surface area (222.3 m(2)/g), demonstrating that they can be used as a bifunctional agent for both MRI and drug carrier. Because of the high substrate loading of the magnetic, dual-porous materials, only a low dosage of the substrate will be acquired for potential practical applications. Hydrophobic zinc(II) phthalocyanine (ZnPC) photosensitizing molecules have been encapsulated into the dual-porous microspheres to form γ-Fe(2)O(3)@meso-SiO(2)-ZnPC microspheres. Biosafety, cellular uptake in HT29 cells, and in vitro MRI of these nanoparticles have been demonstrated. Photocytotoxicity (λ > 610 nm) of the HT29 cells uptaken with γ-Fe(2)O(3)@meso-SiO(2)-ZnPC microspheres has been demonstrated for 20 min illumination.

T(1ρ) relaxation has recently been found to be sensitive to liver fibrosis and has potential to be used for early detection of liver fibrosis and grading. Liver T(1ρ) imaging and accurate mapping are challenging because of the long scan time, respiration motion and high specific absorption rate. Reduction and optimization of spin lock times (TSLs) are an efficient way to reduce scan time and radiofrequency energy deposition of T(1ρ) imaging, but maintain the near-optimal precision of T(1ρ) mapping. This work analyzes the precision in T(1ρ) estimation with limited, in particular two, spin lock times, and explores the feasibility of using two specific operator-selected TSLs for efficient and accurate liver T(1ρ) mapping. Two optimized TSLs were derived by theoretical analysis and numerical simulations first, and tested experimentally by in vivo rat liver T(1ρ) imaging at 3 T. The simulation showed that the TSLs of 1 and 50 ms gave optimal T(1ρ) estimation in a range of 10-100 ms. In the experiment, no significant statistical difference was found between the T(1ρ) maps generated using the optimized two-TSL combination and the maps generated using the six TSLs of [1, 10, 20, 30, 40, 50] ms according to one-way ANOVA analysis (p = 0.1364 for liver and p = 0.8708 for muscle)., (© 2012 Institute of Physics and Engineering in Medicine)

Intra-operative lymphatic mapping and sentinel lymph-adenectomy (LM/SL) maps the lymphatic path from the primary tumor to the regional nodes and permits selective excision of the first sentinel lymph nodes. It is a well established technique to detect occult regional node metastases for melanoma patients and breast cancer patients. In continuing attempts to improve accuracy, most surgeons now combine a dye (such as carbon particles) and radiopharmaceuticals when performing LM/SL. We developed a proto-type of carbon coated superparamagnetic iron oxide nanoparticles (SPIO@C) for sentinel lymph nodes mapping. Compared with combining carbon particles and radiopharmaceuticals for performing LM/SL, there are a number of advantages with our approach: I. SPIO is an MRI contrast agent, thus pre-operative MRI may be used for LM/SL instead of gamma camera. There is no radiation associated with MRI, and MRI offers good tissue contrast and detailed cross-sectional images. II. There will be only needed one injection of SPIO@C nanoparticles, instead of administrating two successive injections of radiopharmaceuticals and carbon particles. III. During the operation, an intra-operative MRI scanner can be used, or more conveniently by a simple magnetometer.

Unlabelled: Abstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2α) (PGF(2α)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR)., Results: Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2α) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2α). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries., Conclusion: These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2α) plays an important role in mediating endothelial dysfunction in RH., Innovation: The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2α) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.

Purpose: To compare the cellular uptake efficiency and cytotoxicity of aminosilane (SiO(2)-NH(2))-coated superparamagnetic iron oxide (SPIO@SiO(2)-NH(2)) nanoparticles with three other types of SPIO nanoparticles coated with SiO(2) (SPIO@SiO(2)), dextran (SPIO@dextran), or bare SPIO in mammalian cell lines., Materials and Methods: Four types of monodispersed SPIO nanoparticles with a SPIO core size of 7 nm and an overall size in a range of 7-15 nm were synthesized. The mammalian cell lines of MCF-7, MDA-MB-231, HT-29, RAW264.7, L929, HepG2, PC-3, U-87 MG, and mouse mesenchymal stem cells (MSCs) were incubated with four types of SPIO nanoparticles for 24 hours in the serum-free culture medium Dulbecco's modified Eagle's medium (DMEM) with 4.5 μg/mL iron concentration. The cellular uptake efficiencies of SPIO nanoparticles were compared by Prussian blue staining and intracellular iron quantification. In vitro magnetic resonance imaging of MSC pellets after SPIO labeling was performed at 3 T. The effect of each SPIO nanoparticle on the cell viability of RAW 264.7 (mouse monocyte/macrophage) cells was also evaluated., Results: Transmission electron microscopy demonstrated surface coating with SiO(2)-NH(2), SiO(2), and dextran prevented SPIO nanoparticle aggregation in DMEM culture medium. MCF-7, MDA-MB-231, and HT-29 cells failed to show notable iron uptake. For all the remaining six cell lines, Prussian blue staining and intracellular iron quantification demonstrated that SPIO@ SiO(2)-NH(2) nanoparticles had the highest cellular uptake efficiency. SPIO@SiO(2)-NH(2), bare SPIO, and SPIO@dextran nanoparticles did not affect RAW 264.7 cell viability up to 200 μg Fe/mL, while SPIO@SiO(2) reduced RAW 264.7 cell viability from 10 to 200 μg Fe/mL in a dose-dependent manner., Conclusion: Cellular uptake efficiency of SPIO nanoparticles depends on both the cell type and SPIO surface characteristics. Aminosilane surface coating enhanced the cellular uptake efficiency without inducing cytotoxicity in a number of cell lines.

We found that Icaritin, an intestinal metabolite of Epimedium-derived flavonoids (EF) enhanced osteoblastic differentiation of mesenchymal stem cells (MSCs) only under osteogenic induction conditions. We also demonstrated its effect on inhibition of adipogenic differentiation of MSCs. Unlike the findings of others on EF compounds, we showed that Icaritin was unable to promote proliferation, migration and tube like structure formation by human umbilical vein endothelial cells (HUVECs) in vitro. These results suggested that the exogenous phytomolecule Icaritin possessed the potential for enhancing bone formation via its osteopromotive but not an osteoinductive mechanism. Though some flavonoids were shown to regulate the coupling process of angiogenesis and osteogenesis during bone repair, our results suggested that Icaritin did not have direct effect on enhancing angiogenesis in vitro.

B(0) and B(1) field inhomogeneities may generate banding-like artifacts in T(1ρ)-weighted images and hence result in errors of T(1ρ) quantification. Several types of composite spin-lock pulses have been proposed to alleviate such artifacts. In this study, magnetization evolution with T(1ρ) and T(2ρ) relaxation by using these composite spin-lock pulses are theoretically derived. The effectiveness and limitation of each spin-lock pulse are explicitly illustrated in mathematical forms and phantom T(1ρ)-weighted images acquired by using each spin-lock pulse are presented. This study also provides a theoretical framework for T(1ρ) quantification from T(1ρ)-weighted images even with B(0) and B(1) inhomogeneity artifacts.

Superparamagnetic iron oxide (SPIO) MR contrast agents are composed of nano-sized iron oxide crystals coated with dextran or carboxydextran. Two SPIO agents are clinically approved, namely: ferumoxides (Feridex in the USA, Endorem in Europe) with a particle size of 120 to 180 nm, and ferucarbotran (Resovist) with a particle size of about 60 nm. The principal effect of the SPIO particles is on T2* relaxation and thus MR imaging is usually performed using T2/T2*-weighted sequences in which the tissue signal loss is due to the susceptibility effects of the iron oxide core. Enhancement on T1-weighted images can also be seen with the smaller Resovist. Both Feridex and Resovist are approved specifically for MRI of the liver. The difference being that Resovist can be administered as a rapid bolus (and thus can be used with both dynamic and delayed imaging), whereas Feridex needs to be administered as a slow infusion and is used solely in delayed phase imaging. In the liver, these particles are sequestered by phagocytic Kupffer cells in normal reticuloendothelial system (RES), but are not retained in lesions lacking Kupffer cells. Consequently, there are significant differences in T2/T2* relaxation between normal tissue and lesions, resulting in increased lesion conspicuity and detectability. SPIO substantially increase the detectability of hepatic metastases. For focal hepatocellular lesions, SPIO-enhanced MR imaging exhibits slightly better diagnostic performance than dynamic CT. A combination of dynamic and static MR imaging technique using T1- and T2 imaging criteria appears to provide clinically more useful patterns of enhancement. Feridex and Resovist are also used for evaluating macrophage activities in some inflammatory lesions, but their clinical values remain to be further confirmed. The clinical development of Ferumoxtran (Combidex in the USA, Sinerem in Europe), designed for lymph node metastasis evaluation, is currently stopped.

Chemoembolization has been used in the field of interventional oncology. Although practiced widely, it has only recently been demonstrated that the use of transarterial chemoembolization (TACE) provides a survival benefit based on randomized controlled trials. TACE combines the effect of targeted chemotherapy with the effect of ischemic necrosis induced by arterial embolization. Most of the TACE procedures have been based on iodized oil utilizing its microembolic and drug-carrying characteristics. Recently, there have been efforts to improve the delivery of chemotherapeutic agents to a tumor, which leads to the development of drug-eluting particles. In this review, we will describe the properties and efficacy of some chemoembolization agents which are commercially available and/or currently under clinical investigations. The potential and future of this new form of transcatheter arterial therapy for liver cancer will be discussed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The vasculature in the outer annulus supplies only the periphery of the disc so that nutrition to the bulk of the disc, including all the inner annulus and nucleus pulposus, is derived from the vertebral epiphyseal end arteries where nutrients diffuse across the cartilaginous endplate to reach the disc. In this regard the vertebral endplate plays an important role in disc nutrition. Compromise of diffusion of nutrients to the disc cells may play a large part in the progression or even initiation of disc degeneration. Increasing evidence suggests that estrogen deficiency also influence the severity of disc degeneration in post-menopausal females. Structural disorganization of the vertebral endplate occurs with disc degeneration, with the most common endplate changes observed clinically being Schmorl's node. Schmorl's node is more commonly seen in post-menopausal women than younger women. Osteosclerosis, osteonecrosis and fibrosis associated with Schmorl's nodes can impede nutrient diffusion into the disc as well as removal of metabolites from the disc. We hypothesize that menopause negatively affects vertebral endplate quality and induces endplate degeneration. This endplate degeneration decreases nutrients diffusion from vertebral body into discs, and also impedes removal of metabolites, leads to further disc degeneration. To confirm our hypothesis, a cross-sectional post-contrast MRI study can be performed in pre-menopausal and post-menopausal women. If the hypothesis is confirmed, then low dose hormone replacement treatment may retard disc degeneration in post menopausal women and thereby limit the consequences associated with disc degeneration such as low back pain., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: To correlate spin-lattice relaxation time in the rotating frame (T1ρ) measurements with degree of liver fibrosis in a rat model., Materials and Methods: The protocols and procedures were approved by the local Animal Experimentation Ethics Committee. Liver fibrosis was induced with biliary duct ligation (BDL). Two studies, 1 month apart, were performed with a 3-T clinical imager. The first study involved longitudinal magnetic resonance (MR) imaging follow-up of BDL rats (n = 8) and control rats (n = 4) on days 8, 15, 21, and 29 after BDL. The second study involved MR imaging of another group of BDL and control rats (n = 5 for each) on days 24 and 38 after BDL. Hematoxylin-eosin and picrosirius red staining were performed in liver specimens from days 8, 15, 24, and 38 after BDL. Repeated-measures analysis of variance was used, and treatment groups were compared (Bonferroni adjustment)., Results: On day 8, there were proliferation of bile duct and inflammatory cell infiltration around portal triads. While there was overlap, BDL rats (n = 8) demonstrated higher mean liver T1ρ values than did control rats (n = 4) on day 8 (46.7 msec ± 2.9 [standard deviation] vs 44.7 msec ± 1.2, P = .4). On day 15, BDL rats demonstrated liver fibrosis with a background of inflammatory infiltration. On day 15, mean T1ρ values in BDL rats could be largely separated from those in control rats (52.6 msec ± 6.0 vs 43.8 msec ± 1.5, P = .02). On day 24, BDL rats had liver T1ρ values 23.5% higher than in control rats (n = 5 for each group, P = .0007). Histomorphometric analysis showed that collagen content increased after surgery from days 8 to 24 (n = 6 for each group, P < .0001), with no further increase between days 24 and 38 (n = 6 for each group, P >.99)., Conclusion: In this model, liver fibrosis was detected with T1ρ MR imaging; the degree of fibrosis was correlated with degree of increase in T1ρ measurements., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101638/-/DC1., (RSNA, 2011)

Objective: To investigate the biocompatibility of human platelet-rich plasma (PRP) and human dental pulp cells (DPCs), and the effect of human platelet-rich plasma on the mineralization of human dental pulp cells in vivo., Methods: DPCs were isolated from healthy dental pulp, and identified by immunostaining of vimentin and cytokeratin. PRP was obtained from healthy volunteer donors by traditional two-step centrifugation. The forth passage of DPCs and PRP were mixed well and activated, and then transplanted subcutaneously in 5-week female nude mice. The groups which were implanted with PRP alone or DPCs alone were used as controls. The animals were sacrificed after 4 weeks and 8 weeks post-transplantation, and the histological and immunohistostaining examinations were used to evaluate the effect of PRP on the mineralization of DPCs., Results: Immunostaining showed that DPCs were positive for vimentin and negative for cytokeratin. In vivo assay showed that the newly formed mineralized tissues were only found in PRP combined with DPCs group after 4 weeks and 8 weeks, while newly formed tissues were not observed in PRP alone or DPCs alone groups. HE staining showed the mineralized tissues were found in PRP+DPCs samples. Immunohistochemistry staining showed these mineralized tissues were positive for osteopontin(OPN), osteocalcin(OC) and collagen I (COLI)., Conclusion: PRP had good biocompatibility with DPCs, and could induce the mineralization of DPCs. The study suggests that platelet-rich plasma can be used as a scaffold for pulp capping.

We herein report a comparative study of mesenchymal stem cell (MSC) labeling using spherical superparamagnetic iron oxide (SPIO) nanoparticles containing different coatings, namely, organosilica, dextran, and poly(ethylene glycol) (PEG). These nanomaterials possess a similar SPIO core size of 6-7 nm. Together with their coatings, the overall sizes are 10-15 nm for all SPIO@SiO₂, SPIO@dextran, and SPIO@PEG nanoparticles. These nanoparticles were investigated for their efficacies to be uptaken by rabbit bone marrow-derived MSCs without any transfecting agent. Experimentally, both SPIO@SiO₂ and SPIO@PEG nanoparticles could be successfully uptaken by MSCs while the SPIO@dextran nanoparticles demonstrated limited labeling efficiency. The labeling durability of SPIO@SiO₂ and SPIO@PEG nanoparticles in MSCs after three weeks of culture were compared by Prussian blue staining tests. SPIO@SiO₂ nanoparticles demonstrated more blue staining than SPIO@PEG nanoparticles, rendering them better materials for MSCs labeling by direct uptake when durable intracellullar retention of SPIO is desired.

Purpose: To study the relationship between hip bone mineral density (BMD), lumbar disc degeneration, and lumbar disc space narrowing in elderly subjects., Materials and Methods: The study cohort comprised 196 females and 163 males (age range, 67-89 years) with no age difference between the two groups. Anteroposterior total hip areal BMD was measured with DXA and lumbar spine MRI was acquired using a 1.5 Tesla scanner. Lumbar disc degeneration was assessed using an eight-level grading system wherein each grade represents a stepwise progression from normal disc to severe disc degeneration and disc space narrowing., Results: After controlling for the age effect, no significant relationship was observed between total hip T-score status and severity of disc degeneration. There was no significant difference in total hip BMD in the subjects with or without the disc space narrowing (P < 0.05). Female subjects are more likely to have a narrowed disc space than males at all levels, and being statistically significant at L3/4 and L4/5 levels, and with an overall significance of P = 0.007., Conclusion: There was no association observed between hip BMD and lumbar disc degeneration. Elderly females were more likely to have a narrowed lumbar disc space than elderly males., (Copyright © 2011 Wiley-Liss, Inc.)

A litterbag experiment was conducted to study the decomposition of Cunninghamia lanceolata leaf litter under ambient and reduced UV-B radiation (22.1% below ambient). Comparing with ambient treatment, the reduced treatment decreased the decomposition rate of C. lanceolata leaf litter by 69.6% (P<0.001), making the relative contents of nitrogen (N), phosphorus (P), and lignin in the litter increased by 150%, 83.3%, and 13.8%, respectively, and the release of potassium (K) and carbon (C) slowed down. In the process of litter decomposition, photo-degradation of lignin didn't play crucial role. The results suggested that UV-B radiation could accelerate the decomposition rate of C. lanceolata leaf litter, promote the release of N, P, K, and C from it, and increase the nutrients turnover rate in litter layer as well as the carbon flux on the ground, giving potential effects on the function of C. lanceolata forest as a carbon source or sink in humid subtropical China.

The objective evaluation of the color and shade in stained images remains unsolved and is frequently and extensively encountered in biomedical studies. Most of the evaluations on the color and shade in the stained images are currently performed by subjective grading, which is prone to be affected by inter-reader variation. This paper introduces a novel approach to automatically quantify the color and shade in the stained histological image based on its similarity map in the CIELAB color space with respect to a user specified reference color. The proposed algorithm was applied on three datasets, i.e., a phantom image, the Prussian blue staining of human osteosarcoma cell culture, and histological sections of the Prussian blue stained rat kidney, liver and spleen. The result shows that our method is able to represent the color and shade as a numerical value that correlated well with human perception., (Copyright © 2011 International Society for Advancement of Cytometry.)

The terahertz band lies between the microwave and infrared regions of the electromagnetic spectrum. This radiation has very low photon energy and thus it does not pose any ionization hazard for biological tissues. It is strongly attenuated by water and very sensitive to water content. Unique absorption spectra due to intermolecular vibrations in this region have been found in different biological materials. These unique features make terahertz imaging very attractive for medical applications in order to provide complimentary information to existing imaging techniques. There has been an increasing interest in terahertz imaging and spectroscopy of biologically related applications within the last few years and more and more terahertz spectra are being reported. This paper introduces terahertz technology and provides a short review of recent advances in terahertz imaging and spectroscopy techniques, and a number of applications such as molecular spectroscopy, tissue characterization and skin imaging are discussed.

This article reports the fabrication of mesoporous Fe(3)O(4) nano/microspheres with a high surface area value (163 m(2)/g, Brunauer-Emmett-Teller) and demonstrates their use for drug loading, release, and magnetic resonance imaging (MRI). These monodispersed, mesoporous Fe(3)O(4) nano/microspheres with controllable average sizes ranging from 50 to 200 nm were synthesized using a Fe(3)O(4)/poly(acrylic acid) hybrid sphere template and subsequent silica shell formation and removal. We found that the SiO(2) coating is a crucial step for the successful synthesis of uniform mesoporous Fe(3)O(4) nano/microspheres. The as-synthesized mesoporous Fe(3)O(4) nanospheres show a high magnetic saturation value (M(s) = 48.6 emu/g) and could be used as MRI contrast agents (r(2) = 36.3 s(-1) mM(-1)). Trypan blue exclusion and MTT assay (see Supporting Information ) cytotoxicity analyses of the nanospheres based on HepG2 and MDCK cells showed that the products were biocompatible, with a lower toxicity than lipofectamine (positive control). Hydrophilic ibuprofen and hydrophobic zinc(II) phthalocyanine drug loading into mesoporous Fe(3)O(4) nanospheres and selected release experiments were successfully achieved. The potential use of mesoporous Fe(3)O(4) nanospheres in biomedical applications, in light of the nano/microspheres' efficient drug loading and release, MRI, and low cytotoxicity, has been demonstrated. It is envisaged that mesoporous Fe(3)O(4) nanospheres can be used as drug carriers and MRI contrast agents for the reticuloendothelial system; they can also be delivered locally, such as via a selective catheter.

We have previously demonstrated that terahertz pulsed imaging is able to distinguish between rat tissues from different healthy organs. In this paper we report our measurements of healthy and cirrhotic liver tissues using terahertz reflection spectroscopy. The water content of the fresh tissue samples was also measured in order to investigate the correlations between the terahertz properties, water content, structural changes and cirrhosis. Finally, the samples were fixed in formalin to determine whether water was the sole source of image contrast in this study. We found that the cirrhotic tissue had a higher water content and absorption coefficient than the normal tissue and that even after formalin fixing there were significant differences between the normal and cirrhotic tissues' terahertz properties. Our results show that terahertz pulsed imaging can distinguish between healthy and diseased tissue due to differences in absorption originating from both water content and tissue structure.

Medical imaging can help answer key questions that arise during the drug development process. The role of medical imaging in new drug clinical trials includes identification of likely responders; detection and diagnosis of lesions and evaluation of their severity; and therapy monitoring and follow-up. Nuclear imaging techniques such as PET can be used to monitor drug pharmacokinetics and distribution and study specific molecular endpoints. In assessing drug efficacy, imaging biomarkers and imaging surrogate endpoints can be more objective and faster to measure than clinical outcomes, and allow small group sizes, quick results and good statistical power. Imaging also has important role in drug safety monitoring, particularly when there is no other suitable biomarkers available. Despite the long history of radiological sciences, its application to the drug development process is relatively recent. This review highlights the processes, opportunities, and challenges of medical imaging in new drug development.

Object: Anterior temporal lobe resection plus amygdalohippocampectomy can cause damage to the anterior portion of the optic radiation, also known as the Meyer loop, resulting in homonymous superior quadrantanopia. Magnetic resonance diffusion tensor tractography (DTT) of the Meyer loop can help in surgical planning. In this study, the distance of the anterior tip of the Meyer loop to the temporal lobe pole (ML-TP) in the Southern Chinese population was assessed., Methods: The authors studied 16 Southern Chinese individuals (8 men and 8 women; mean age 45.6 years, range 21-60 years). Diffusion tensor images were obtained with a 3-T MR imaging system using a single-shot spin echo echo planar imaging sequence. Two trained operators, one neurosurgeon (Operator A) and one radiologist (Operator B), carried out the DTT analysis with software iPlan (BrainLAB) and FiberTrak (Philips)., Results: For the 32 temporal lobes, the intraclass correlation coefficient (ICC) of the 2 operators' results using iPlan was 0.96, while that of Operator A using iPlan and Operator B using FiberTrak was 0.75. The ICC of Operator B using iPlan and FiberTrak was 0.81. The ML-TP distance of normal lobes (30 lobes [2 lobes that previously underwent surgery were excluded]) was 36.3±5.5 mm (range 26.6-48.9 mm), 36.3±5.3 mm (range 26.8-48.2 mm), and 35.9±6.4 mm (range 20.8-48.4 mm) for Operator A using iPlan, Operator B using iPlan, and Operator B using FiberTrak, respectively (p>0.05)., Conclusions: The 2 operators reached good agreement on ML-TP distance measurement using DTT. The DDT results can be more software dependent than operator dependent. The measurement with FiberTrak demonstrated larger range and standard deviation than measurement with iPlan.

Lumbar spine disk degeneration is a common musculoskeletal condition, the prevalence of which increases with age (1-3). Disk degeneration can progress to disk herniation, spinal canal stenosis, and, in conjunction with facet joint arthrosis, degenerative spondylolisthesis. It remains not fully understood what factors initiate and influence the progression of disk degeneration. Nevertheless, there is general agreement that spinal mechanical stress accelerates the development of disk degeneration and increases the likelihood of disk herniation (4-6). Increasing evidence suggests that sex hormones also influence the severity of disk degeneration., (© RSNA, 2010.)

Magnetic FeNi3 nanochains were synthesized by reducing iron(III) acetylacetonate and nickel(II) acetylacetonate with hydrazine in ethylene glycol solution without any template under a rapid and economical microwave irradiation. The morphology and composition of the as-prepared products were characterized by field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and elemental mapping. The size of the aligned nanospheres in the magnetic FeNi3 chains could be adjusted from 150 to 550 nm by increasing the amounts of the precursors. The length of the nanochain is about several tens of micrometers. The ratio of the precursors plays an important role in the formation of FeNi3 nanostructures. Magnetic measurement reveals that the FeNi3 nanochains show enhanced coercivity and saturation magnetization. The formation mechanism of the product is discussed. Toxicity tests of FeNi3 nanochains show that the as-prepared nanochains are nontoxic to zebrafish larvae. In vitro magnetic resonance imaging (MRI) confirms the effectiveness of the FeNi3 nanochains as sensitive MRI probes.

Background: Osteochondral lesion (OCL) treatment is based on patient symptoms, lesion size, and lesion stability. MRI of talar OCL identifies the presence and the characteristics of the lesion and attempts to establish lesion stability. We report our experience that the depiction of OCL can be improved by using a small field-of-view (FOV) surface coil., Materials and Methods: We studied 24 patients (25 lesions) with OCLs of the talar dome. Standard FOV MRI followed by small FOV MRI of the ankle was performed at 1.5-T. Standard FOV MRI was taken using a quadrature knee coil or a 21 cm x 53 cm circularly flexible coil. A 4-cm circular polarized receiver surface coil was used for small FOV imaging. Twelve aspects characteristics of OCLs were assessed, including lesion matrix, margin characteristics, lesion cortical surface, cartilage surface, cartilage depth, cartilage signal, cartilage integrity, and osteochondral gap., Results: Small FOV MRI provided more detailed morphological information of talar OCL. The following differences were noted. Small FOV coil imaging reclassified cortical surface from flush to depressed in seven cases and from unclear in two cases to flush in one case and proud in the other. Small FOV coil imaging reclassified cartilage integrity from unclear to intact in 16 cases and from unclear to fracture in three cases. For assessment of osteochondral gap, small FOV coil MR imaging reclassified from absent to present in two cases and from unclear to absent in one case. For osteochondral fragment, small FOV coil MR imaging reclassified assessment from absent to present in three cases and from unclear to absent in three cases., Conclusion: Small FOV coil improved visualization of the talar OCL.

Purpose: To determine whether low-intensity pulsed ultrasound (LIPUS) is able to facilitate the uptake of a superparamagnetic iron oxide (SPIO) nanomaterial by cells that do not express high endocytosis capacity., Materials and Methods: The human osteosarcoma cell line U2OS and a silica-coated SPIO functionalized peripherally with amines groups (overall diameter 8 nm) were used in this study. Adherent U2OS cells were labeled with SPIO by incubating with culture media containing the SPIO at 4.5 microg[Fe]/mL. LIPUS with the same parameters as those used in clinical application to accelerate bone fracture healing (1.5 MHz, duty cycle 1:4, spatial-average temporal-average intensity 30 mW/cm(2)) was applied to the cells at the beginning of the labeling process for 0, 0.5, 1, or 3 hours. The total incubation time with SPIO was 12 hours. SPIO labeling efficiency was evaluated with Prussian blue staining and a blueness measurement method, and magnetic resonance imaging (MRI) of cell pellets via measuring areas of SPIO-induced signal void., Results: Both Prussian blue staining and in vitro MRI demonstrated that LIPUS application increased the SPIO nanomaterial labeling efficiency for U2OS cells in an exposure-duration-dependent manner., Conclusion: This study is a "proof of concept" that LIPUS can facilitate the cellular take-up of SPIO nanomaterial.

Most traditional methods for T(1) map estimation in MRI with fast low-angle-shot sequences are aimed at high efficiency by compromising the fitting accuracy. In this paper, the fundamental problem of parameter estimation in fast low-angle-shot MRI was re-examined, and an accurate and fast optimization approach, named concatenated optimization for parameter estimation, was proposed for the regression of data points acquired with multiple flip angles. The initial estimation of T(1) was obtained from the linear regression, followed by the constrained nonlinear regression based on the initial estimates. This heterogeneous initialization strategy improves the fitting accuracy and reduces the computational time. A computationally efficient implementation of concatenated optimization for parameter estimation was achieved based on the graphic processing unit, named as concatenated optimization for parameter estimation graphic processing unit. In experimental comparison with Fram's method and the Fitter Tool in Jim, the proposed methods are capable of achieving significantly higher efficiency and more accurate estimations., ((c) 2010 Wiley-Liss, Inc.)

Objective: To investigate the possibility of combined non-specific activated splenocytes (aSplenocytes) and cisplatin in treating murine hemangioendothelioma EOMA cell line., Methods: The effects of cisplatin, aSplenocytes or both on EOMA cells were measured by MTT assay and trypan blue exclusive method, respectively. EOMA-bearing mice were established by subcutaneous inoculation of 1.5x10(6) EOMA cells in 6-week old male BALB/c nu/nu mice, divided into untreated control, cisplatin group, aSplenocytes group, and combination group, 5 mice per group. Tumor was treated with 1.5x10(6) aSplenocytes per 100 microL via intratumoral injection, and 24 hours later, followed by cisplatin treatment via intraperitoneal injection. Cisplatin treatment was repeated once a week at the dose of 8 mg/kg of body weight. Tumor volume was measured at indicated time., Results: Both cisplatin and aSplenocytes had inhibitory effects on EOMA cells. 47.7%+/-5.9% EOMA cells were found in 100 micromol/L cisplatin-treated EOMA cells for 24 hours. 42.8%+/-2.6% and 45.3%+/-2.2% EOMA cells were in survival in 1x10(5) /mL aSplenocytes-treated EOMA cells in cell-cell direct contact co-culture system and in transwell system for 48 hours, respectively. When EOMA cells were sensitized with 1x10(5) aSplenocytes in cell-cell direct contact system or in transwell system for 24 hours, followed with 100 micromol/L cisplatin for additional 24 hours, only 25.0%+/-2.7% and 27.5%+/-3.8% EOMA cells were in survival. Compared with single-agent alone treatments, aSplenocytes plus cisplatin significantly inhibited the growth of EOMA cells (P<0.05). There was no significant difference in EOMA cell survival between the two co-culture systems (P>0.05). In vivo assay showed the tumor volume was (680.3+/-68.0) mm3, (825.2+/-71.8) mm3, (535.3+/-74.5) mm3 and (351.5+/-79.5) mm3 in the control, aSplenocytes, cisplatin and aSplenocytes plus cisplatin group, respectively, on the 18 th day after treatment. aSplenocytes plus cisplatin markedly delayed EOMA tumor growth (P<0.05)., Conclusion: aSplenocytes could enhance the cytotoxicity of cisplatin in EOMA cells in vitro and in vivo.

Purpose: To investigate the cause of reduced vertebral perfusion in a rat ovariectomy model., Materials and Methods: Experimental protocol was approved by the local Animal Experiment Ethics Committee. Twenty-two Sprague-Dawley rats were studied. Computed tomographic bone densitometry and magnetic resonance perfusion imaging were performed at baseline and 2, 4, and 8 weeks after ovariectomy (n = 11) or sham surgery (n = 11). Perfusion parameters analyzed were maximum enhancement (E(max)) and enhancement slope (E(slope)). After the animals were sacrificed, the aorta and femoral artery were analyzed for vessel reactivity, and the lumbar vertebrae were analyzed for marrow content., Results: In control rats, bone mineral density (BMD), E(max), and E(slope) remained constant. In ovariectomy rats, a comparable reduction in BMD and the perfusion parameters at two weeks post-ovariectomy (BMD, 9.3%; E(max), 11.6%; E(slope), 9%) was seen 2 weeks after ovariectomy, and further reductions were seen 4 weeks (BMD, 17.5%; E(max), 15.6%; E(slope), 33%) and 8 weeks (BMD, 18.8%; E(max), 14.2%; E(slope), 33%) after ovariectomy. Endothelial dysfunction was observed in both the aorta and femoral artery of the ovariectomy group but not of the control group. Increased marrow fat area was seen in the ovariectomy group (52.9% vs 21.6%; P < .01) owing to an increase in fat cell number. Decreased erythropoetic marrow area (32.5% vs 48.6%; P < .05) was also observed in the ovariectomy group., Conclusion: Reduced bone perfusion occurs in synchrony with reduced BMD. The most likely causes of reduced bone perfusion are a reduction in the amount of erythropoetic marrow and endothelial dysfunction after ovariectomy., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090608/-/DC1., ((c) RSNA, 2010)

Background: Gefitinib is one of the small molecule inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR TKIs). Clinical trials have demonstrated it is effective for treatment of a subset of patients with advanced non-small cell lung cancer (NSCLC). Gefitinib has been generally considered to be a relatively safe agent. Besides a small proportion of fatal interstitial pneumonia, the common adverse drug reactions of gefitinib include diarrhea and skin rash, which are generally mild and reversible. Herein, we report the first two cases of brain metastasis hemorrhage that might be involved with the use of gefitinib., Case Presentation: Two patients with brain metastasis from NSCLC developed brain hemorrhage after gefitinib therapy. The hemorrhage in one case occurred one month after gefitinib combined with whole brain radiation therapy (WBRT), and in the another case hemorrhage developed slowly within brain metastases eight months post gefitinib monotherapy for diffuse pulmonary metastasis from a lung cancer undergone surgical removal previously., Conclusion: We speculate brain hemorrhage could be one of the adverse drug reactions of gefitinib treatment for NSCLC and suggest clinicians be aware of this possible rare entity. More data are needed to confirm our findings, especially when gefitinib is used in the settings of brain metastases from NSCLC or other origins.

Small polyhedral superparamagnetic iron oxide (SPIO) nanoparticles (<10 nm) coated with a thin layer of silica were prepared (SPIO@SiO(2) and SPIO@SiO(2)-NH(2)). Surface modification of the small polyhedral silica-coated SPIO nanoparticles with amines led to substantially higher mesenchymal stem cell (MSC) labelling efficiency without the use of additional transfecting agents. Therefore, amine surface-modified nanoparticles (SPIO@ SiO(2)-NH(2)) appeared to be the preferred candidate for MSC labelling. In vitro studies demonstrated that controlled labelling of SPIO@SiO(2) and SPIO@SiO(2)-NH(2) did not cause MSC death or proliferation inhibition. MSCs labelled with SPIO@SiO(2)-NH(2) nanoparticles retained differentiation potential and showed osteogenic, adipogenic and chondrogenic differentiations. The noncytotoxic polyhedral SPIO@SiO(2)-NH(2) nanoparticle-labelled MSCs were successfully implanted in rabbit brain and erector spinae muscle, and demonstrated long-lasting, durable MRI labelling efficacy after 8-12 weeks.

Purpose: To investigate the differences in proximal femoral bone marrow blood perfusion indices between hypertensive and normotensive rats using perfusion magnetic resonance imaging (MRI)., Materials and Methods: Six-month-old male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were used (12 of each). Dynamic contrast-enhanced MRI of the right hip was performed after bolus injection of Gd-DOTA administered through a tail vein cannula. In all, 800 images were acquired at 0.6 sec/image. Regions of interest (ROIs) were drawn comprising the medullary component of proximal femoral shaft and femoral head. MRI maximum enhancement (E(max)) and enhancement slope (E(slope)) were analyzed., Results: The E(max) and E(slope) of proximal femoral shaft and femoral head of SHR were significantly lower than those of WKY (E(max): 107.4 +/- 18.2% vs. 130.6 +/- 21.5%, P = 0.009, and 76.0 +/- 12.5% vs. 97.9 +/- 6.9%, P < 0.001, respectively; E(slope): 3.01 +/- 0.63%/sec vs. 3.75 +/- 0.74%/sec, P = 0.016, and 1.95 +/- 0.33%/sec vs. 2.28 +/- 0.28%/sec, P = 0.012, respectively). The E(max) and E(slope) of femoral head were significantly lower than those of proximal femoral shaft in both SHR and WKY (P < 0.001). In both SHR and WKY, proximal femoral shaft and femoral head had a rather different contrast enhancement pattern., Conclusion: Proximal femoral shaft and femoral head bone marrow blood perfusion indices were significantly lower in hypertensive rats than in normotensive rats. Femoral head bone marrow was less perfused than proximal femoral shaft in both rats.

Objective: To examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid-associated osteonecrotic lesions in rabbits., Methods: Steroid-associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated., Results: Lesion formation without repair was observed at 2 weeks after induction of steroid-associated osteonecrosis. Rabbits displaying destructive repair (DR+) and those displaying reparative osteogenesis (DR-) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR+ rabbits compared with DR- rabbits, whereas the permeability index was significantly higher in DR+ rabbits compared with DR- rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR+ rabbits than in DR- rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR+ rabbits, whereas VEGF expression decreased in DR- rabbits from week 2 to week 6., Conclusion: Continuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously low- level MSCP and uncontrolled VEGF expression during inadequate repair of steroid-associated osteonecrotic lesions.

One-dimensional composite Mn-Fe oxide nanostructures of different sizes (nanoneedles, nanorods, and nanowires) were prepared by a linker-induced organization of manganese-doped iron oxide nanoparticles. The nanostructures were obtained by the treatment of MnFe(2)O(4) nanoparticles in the presence of cystamine. The average lengths of nanoneedle, nanorod, and nanowire are approximately 400, 800, and 1000 nm, respectively. High-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray (EDX) spectroscopy, and inductively coupled plasma-optical emission spectroscopy (ICP-OES) were employed to characterize the morphologies and the elemental contents of the nanostructures. As an example of their potential applications, these nanostructures were explored as the cell-labeling agents for magnetic resonance imaging (MRI). The magnetic contrast properties of the nanostructures were characterized by a 1.5 T (Tesla) whole body MR system. 10 microg/mL of the nanostructures caused substantial negative contrast. After in vitro incubation, the nanostructures could be effectively incorporated into the cells of a monocyte/macrophage cell line (RAW264.7). These cells' viability and proliferation potential were not affected when the labeling concentration was less than 50 microg/mL.

Objective: To investigate the feasibility of establishing a murine hemangioma model with injection of recombinant adeo-associated virus mediated human vascular endothelial growth factor-121 (rAAV-hVEGF(121)) gene., Methods: rAAV-hVEGF(121) was constructed, identified and then implanted to the left back ear of each mouse (1.0 x 10(11)VG in 50 microl per mouse and 10 nude mice received the injection), the rights served as controls with an injection of the same volume of phosphate buffered solution (PBS). The skin color and swelling of left back ear were observed every other day. Histological examination was carried out after mice were sacrificed 2, 4, 6, 8, 12 weeks after injection., Results: The rAAV-hVEGF(121) was correctly constructed and confirmed by restriction endonuclease analysis, polymerase chain reaction and DNA sequencing analysis. The skin of left back ear became red 2 weeks after injection and gradually exhibited a red lump which was at its utmost 12 weeks after injection. Such phenomena were not observed in right back ear. Histological examinations showed aggregates of endothelial cells by 2 weeks and at 8 weeks the swollen tissue contained many cysts filled with a mass of red cells. CD-34 staining suggested most of the newly-formed cells were endothelial cells., Conclusions: A hemangioma model was established in mice with injection of recombinant rAAV-hVEGF(121) gene.

Objective: Investigated the efficacy of Avastin on murine hemangioendothelioma in vitro and in vivo using a mouse hemangioendothelioma-derived cell line----EOMA., Methods: The in vitro effect of Avastin on cell proliferation of EOMA cell line was measured by CCK-8 assay at 0, 50, 100, 200 mg/L concentration of Avastin. When tumors produced by subcutaneous injection of EOMA cells reached a volume of 100 mm(3), animals were treated by intra-tumor injection with Avastin (1 mg/kg body weight) or with vehicle alone (PBS) twice a week. Mice were weighted and tumors were measured three times weekly. At the end of the experiment, the mice were sacrificed and their tumors were excised and processed for histology. Immunohistochemical study of apoptosis was conducted using a TUNEL kit, tumor cell proliferation was assessed with anti-proliferating cell nuclear antigen (PCNA) antibody. Cardiac puncture was performed under deep anesthesia for collection of serum, serum vascular endothelial growth factor (VEGF) level was tested by VEGF-ELISA assay., Results: Avastin exhibited cell inhibited rate of 24.21%, 26.26% and 34.58% at 50, 100 and 200 mg/L, respectively. When experiment was terminated, the tumor volume in the PBS-treated mice was (1 860.10+/-146.96) mm3, being significantly larger than that in the mice that were treated by Avastin [(681.45+/-63.01) mm3, P<0.01]. Avastin-treated tumors showed decreased tumor cell proliferation and increased cell apoptosis. The VEGF level in mice treated with Avastin [(594.65+/-118.79) ng/L] was significantly lower than that in PBS-treated mice [(802.24+/-238.41) ng/L, P<0.05]., Conclusion: The results suggest that topically applied Avastin provides an effective and safe approach to treat hemangioendotheliomas and might be used as a novel treatment of angiomatous diseases in the future.

Purpose: To investigate the relationship between vertebral blood perfusion and vertebral bone mineral density (BMD) in a rat orchiectomy (ORX) model., Materials and Methods: Nine 6-month-old male Wistar-Kyoto rats were used. Computed tomography (CT) bone densitometry and dynamic MRI were performed at baseline and four weeks post-ORX. MRI was performed on a 1.5 T clinical MR scanner with a small surface coil placed under the rat lumbar spine region. A sagittal midsection of the lumbar spine was prescribed. Dynamic MRI was performed after a bolus injection of gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA) (0.3 mmol/kg) administered through a tail vein cannula. At a temporal resolution of 0.6 seconds, 800 images were acquired. Regions-of-interest were drawn comprising the medullary component of lumbar vertebrae L3-L6. Maximum enhancement was analyzed., Results: Satisfactory CT and MRI data for analysis was obtained in all animals. Vertebral BMD decreased by 16.6% at four weeks post-ORX (1.134 +/- 0.035 vs. 0.946 +/- 0.027 g/cm(3), P = 0.008). MRI maximum enhancement decreased by 17% at four weeks post-ORX (151.5 +/- 12.0% vs. 125.8 +/- 9.9%, P = 0.015)., Conclusion: Vertebral blood perfusion reduction is associated with vertebral BMD reduction in a male rat osteoporosis model. Perfusion MRI provides a new investigative technique for osteoporosis experimental research., ((c) 2008 Wiley-Liss, Inc.)

Background: Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development., Objective: The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development., Methods: ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARgamma2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON+ (with at least one ON lesion) group and ON- (without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON+ rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion)., Results: Local intra-osseous perfusion index was found lower in either ON+ or MON group when compared to either ON- or SON group, whereas the marrow fat cells number and area were much larger in either ON+ or MON group as compared with ON- and SON group. The adipogenic differentiation ability of MSCs and PPARgamma2 expression in either ON+ or MON group were elevated significantly as compared with either ON- or SON group., Conclusion: These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.

Background: Diethylnitrosamine (DENA) is able to induce various benign and malignant liver lesions in rats with a high success rate and a low mortality rate. It provides a more appropriate model that better simulates the various lesions occurring in humans than the usual model of tumor implantations. The aim of the present study was to evaluate MRI liver examination in Sprague-Dawley (SD) rats as a routine method to detect hepatocellular carcinoma (HCC) nodules induced by DENA and to follow up their growth., Methods: Hepatic carcinogenesis was induced in 80 male SD rats using oral DENA solution. All animals were imaged for liver tumor detection with a 1.5 Tesla magnet (Siemens Sonata, Erlangen, Germany) using correspondence scan parameters and a radio-frequency knee coil. Macroscopic examinations were performed along the axial MRI sections to evaluate magnetic resonance imaging (MRI) findings, and histopathological assessment was also performed., Results: No false negative results were obtained on MR images. Hepatic tumors in 72 rats were confirmed macroscopically and 68 rats were detected by MRI till the 20th week. The smallest and the largest nodules detected by MRI were 2 mm and 37 mm in diameter respectively. The agreement rate of MRI with macroscopic observation was 39.1% and 97.4% respectively for 2 mm to 5 mm and more than 5 mm nodules., Conclusions: The hepatic tumor induced by DENA provides a more representative range of tumors for imaging diagnosis and interventional treatment. MRI is the best approach for scrutinizing pathological changes of rat livers in the period of observation.

Objective: To culture and study the osteogenic characteristics of human bone marrow-derived mesenchymal stem cells (hBMMSCs)., Methods: hBMMSCs were separated and cultured from human iliac crest marrow. Growth kinetics of hBMMSCs was studied by growth curve. Under the osteoinductive culture, osteogenic differentiation of hBMMSCs was tested by alkaline phosphatase (ALP). Osteogenic functions of hBMMSCs in vitro and in vivo were also respectively detected by von Kossa stain and by transplanting hydroxyapatite/tricalcium phosphate ceramics (HA/TCP) with hBMMSCs., Results: hBMMSCs were cultured successfully. The growth curve of the second passage of BMMSCs indicated that the time of population doublings was about 3.5 days. The results of ALP stain were evident by the significant increase in ALP activity after hBMMSCs cultured in osteoinductive medium. Some mineralized nodules were detected by von Kossa stain at nineteenth day of osteoinductive culture. In vivo assay, histological evalution showed bone formation in 3 months after grafts of HA/TCP with hBMMSCs., Conclusions: Osteoinductive solution can induce hBMMSCs to differentiate osteogenetic cell lines. Mineralized nodules and bone formation were found in vitro and in vivo assay. The results demonstrate that hBMMSCs have the potential for osteogenesis.