Liang Bl

The utility of diffusion-weighted MR imaging in cervical cancer

PURPOSE To investigate the value of diffusion-weighted MR imaging (DWI) in detection of cervical cancer, and to determine the diagnostic accuracy of apparent diffusion coefficient (ADC) values for evaluating cervical cancer before and after chemoradiotherapy. MATERIALS AND METHODS Thirty-three patients with cervical squamous carcinoma and 20 patients with other pelvic abnormalities underwent diffusion-weighted imaging (DWI) in addition to routine MR imaging. The ADC values of normal cervical tissue, cervical area before and after chemoradiotherapy were measured and compared. Receiver operating characteristic (ROC) analysis was employed to investigate whether ADC values could help in discrimination among normal cervical tissue, cervical cancer before and after therapy, and to obtain the optimal ADC threshold value. RESULTS Cervical cancer lesion demonstrated obviously hyperintensity on DWI images. The mean ADC value of cervical carcinoma (1.110+/-0.175 x 10(-3)mm(2)/s) was significantly lower than that of normal cervical tissue (1.593+/-0.151 x 10(-3)mm(2)/s) (P<0.001). The mean ADC value of the cervical area in 22 patients treated by chemoradiotherapy (1.436+/-0.129 x 10(-3)mm(2)/s) was significantly higher than that before therapy (1.013+/-0.094 x 10(-3)mm(2)/s) (P<0.001). The difference of ADC values between normal cervical tissue and cervical area after therapy was statistically significant (P<0.01). The optimal ADC threshold values for distinguishing between normal cervical tissue and cervical carcinoma was 1.359 x 10(-3)mm(2)/s, between cervical area before and after therapy was 1.255 x 10(-3)mm(2)/s, between normal cervical tissue and cervical area after therapy was 1.525 x 10(-3)mm(2)/s. The sensitivity and specificity were 100% and 84.8%, 95.5% and 100%, 70% and 81.8%, respectively. CONCLUSION DWI can be applied for the detection of cervical cancer because of its superior disease contrast with normal tissue. The measurement of the ADC values can be a useful tool to monitor the response to therapy for cervical carcinoma.

Targeting EGFR-overexpressing tumor cells using Cetuximab-immunomicelles loaded with doxorubicin and superparamagnetic iron oxide

Epidermal growth factor receptor (EGFR), a cellular transmembrane receptor, plays a key role in cell proliferation and is linked to a poor prognosis in various human cancers. In this study, we constructed Cetuximab-immunomicelles in which the anti-EGFR monoclonal antibody was linked to poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-PCL) nanomicelles that were loaded with doxorubicin (DOX) and superparamagnetic iron oxide (SPIO). The specific interactions between EGFR-overexpressing tumor cells (A431) and immunomicelles were observed using confocal laser scanning microscopy (CLSM) and flow cytometry. Furthermore, the capacity of transporting SPIO into tumor cells using these immunomicelles was evaluated with a 1.5 T clinical magnetic resonance imaging (MRI) scanner. It was found that the acquired MRI T2 signal intensity of A431 cells that were treated with the SPIO-loaded and antibody-functionalized micelles decreased significantly. Using the thiazolyl blue tetrazolium bromide (MTT) assay, we also demonstrated that the immunomicelles inhibited cell proliferation more effectively than their nontargeting counterparts. Our results suggest that Cetuximab-immunomicelles are a useful delivery vehicle for DOX and SPIO to EGFR-overexpressing tumor cells in vitro and that Cetuximab-immunomicelles can serve as a MRI-visible and targeted drug delivery agent for better tumor imaging and therapy.

MR Neurography: T1 and T2 Measurements in Acute Peripheral Nerve Traction Injury in Rabbits

PURPOSE To prospectively evaluate magnetic resonance (MR) signal abnormalities and the time course of T1 and T2 values in a rabbit model of acute nerve traction injury with histologic and functional recovery correlation. MATERIALS AND METHODS All experimental protocols were approved by the institutional animal use and care committee. Acute traction injury was produced in the sciatic nerve of one hind limb in each of 28 rabbits. The contralateral sham-operated nerves served as controls. Sequential MR imaging and T1 and T2 measurements, as well as measurements of functional changes, were obtained over a 70-day follow-up period, with histologic assessments performed at regular intervals. Signal abnormalities and the time course of T1 and T2 values were observed in the proximal, traction, and distal portions of the injured nerves and the sham-operated nerves, and were compared with each other. RESULTS Nerves with acute traction injury showed visible hyperintense signals on T2-weighted images and had prolonged T1 and T2 values. Differences of T1 and T2 values were dependent on the sites along the same injured nerve, with the most pronounced and prolonged phase of T1 and T2 increases (peak values of 1333 msec +/- 46 and 79 msec +/- 3.7, respectively) observed in the most severely damaged portion of the injured nerve. T1 and T2 values and functional changes after nerve injury showed a similar time course. A return of T1 and T2 signals to normal values correlated with functional improvement. CONCLUSION MR imaging could be used to help predict the degree of nerve damage and monitor the process of nerve recovery in acute peripheral nerve traction injury. (c) RSNA, 2010.

A pH-sensitive polymeric nanovesicle based on biodegradable poly(ethylene glycol)-b-poly(2-(diisopropylamino)ethyl aspartate) as a MRI-visible drug delivery system

Diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable 2-(diisopropylamino)ethanol grafted poly(L-aspartic acid) (PAsp(DIP)) were synthesized and evaluated as a MRI-visible and pH-sensitive drug delivery system. The copolymers can self-assemble into stable vesicles in aqueous solutions at neutral pH, resembling the physiological environment, whereas they disassemble in acidic endosomal/lysosomal compartments of tumor cells to achieve rapid drug release. The anticancer drug doxorubicin (DOX) and hydrophilic superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated inside the inner aqueous core of the vesicles for cancer therapy and MR imaging, respectively. In vitrodrug release studies showed that the DOX release from the pH-sensitive vesicles was significantly faster at pH 5.0 than at pH 7.4. SPIONs clustering inside the inner aqueous core of the vesicles resulted in a high spin–spin (T2) relaxivity. Cell culture studies showed that the DOX-SPION-loaded vesicles could be effectively internalized by human hepatic cancer Bel 7402 cells, and DOX could be rapidly released from vesicles inside lysosomal compartments and then migrated into nuclei. Consequently effective suppression of cancer cell growth was detected. This study demonstrated the potential of the biodegradable DOX-SPION-loaded pH-sensitive vesicles as an effective multifunctional nanomedicine platform for cancer therapy due to their pH-triggerable drug release and high MRI sensitivity.

Effects and Safety of Allogenic Mesenchymal Stem Cell Intravenous Infusion in Active Ankylosing Spondylitis Patients who Failed NSAIDs: A 20-Week Clinical Trial

Our objective was to evaluate the feasibility, safety, and efficacy of intravenous (IV) infusion of allogenic mesenchymal stem cells (MSCs) in ankylosing spondylitis (AS) patients who are refractory to or cannot tolerate the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). AS patients enrolled in this study received four IV infusions of MSCs on days 0, 7, 14, and 21. The percentage of ASAS20 responders (the primary endpoint) at the fourth week and the mean ASAS20 response duration (the secondary endpoint) were used to assess treatment response to MSC infusion and duration of the therapeutic effects. Ankylosing Spondylitis Disease Activity Score Containing C-reactive Protein (ASDAS-CRP) and other preestablished evaluation indices were also adopted to evaluate the clinical effects. Magnetic resonance imaging (MRI) was performed to detect changes of bone marrow edema in the spine. The safety of this treatment was also evaluated. Thirty-one patients were included, and the percentage of ASAS20 responders reached 77.4% at the fourth week, and the mean ASAS20 response duration was 7.1 weeks. The mean ASDAS-CRP score decreased from 3.6 ± 0.6 to 2.4 ± 0.5 at the fourth week and then increased to 3.2 ± 0.8 at the 20th week. The average total inflammation extent (TIE) detected by MRI decreased from 533,482.5 at baseline to 480,692.3 at the fourth week (p > 0.05) and 400,547.2 at the 20th week (p < 0.05). No adverse effects were noted. IV infusion of MSCs is a feasible, safe, and promising treatment for patients with AS.

Apparent diffusion coefficient values of necrotic and solid portion of lymph nodes: differential diagnostic value in cervical lymphadenopathy.

AIM To evaluate whether the analysis of the apparent diffusion coefficient (ADC) values of the necrotic and solid portions of lymph nodes aids differentiation between the causes of cervical lymphadenopathy. MATERIALS AND METHODS Thirty-six patients with cervical lymph node metastasis from head and neck squamous cell carcinomas (SCC), 19 patients with lymphoma, and 23 patients with tuberculous lymphadenitis underwent conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI). The ADC values of necrotic and solid portions of lymph nodes were measured and compared. Receiver operating characteristic (ROC) analysis was employed to investigate whether ADC values could help to discriminate between the causes of cervical lymphadenopathy, and to obtain the optimal ADC threshold values. RESULTS The mean ADC values of the solid portions of metastatic nodes, lymphomatous nodes, and tuberculous nodes were (0.93±0.16)×10(-3)mm(2)/s, (0.64±0.13)×10(-3)mm(2)/s and (1.01±0.11)×10(-3)mm(2)/s, respectively (p<0.01). The mean ADC values of necrosis of metastatic and tuberculous nodes were (2.02±0.36)×10(-3)mm(2)/s and (1.25±0.15)×10(-3)mm(2)/s (p<0.01). By using the ADC value of the solid portion, the optimal ADC threshold values for distinguishing between metastasis and lymphoma, between metastasis and tuberculosis, and between lymphoma and tuberculosis were 0.77×10(-3), 0.98×10(-3) and 0.81×10(-3)mm(2)/s, respectively, and the sensitivities and specificities were 83 and 89%, 70 and 68%, 93 and 100%, respectively. By using ADC values of necrosis, the optimal ADC threshold value for distinguishing between metastasis and tuberculosis was 1.59×10(-3)mm(2)/s, and the sensitivity and specificity were 88 and 100%, respectively. CONCLUSION The ADC values both of the necrotic and solid portions of the lymph nodes are useful in differentiation between the causes of cervical lymphadenopathy. The ADC value of necrosis is especially helpful in discriminating metastasis from tuberculosis.

Development of an MRI-visible nonviral vector for siRNA delivery targeting gastric cancer.

An antibody-directed nonviral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles and a gastric cancer-associated CD44v6 single-chain variable fragment (scFvCD44v6,-PEG-g-PEI-SPION), was constructed as a gastric cancer-targeting and magnetic resonance imaging (MRI)-visible nanocarrier for small interfering RNA (siRNA) delivery. Biophysical characterization of PEG-g-PEI-SPION and scFvCD44v6-PEG-g-PEI-SPION was carried out, including siRNA condensation capacity, cell viability, and transfection efficiency. Both the targeting and nontargeting nanocarriers were effective for transferring siRNA in vitro. The cellular uptake and distribution of nanoparticles complexed with siRNA was analyzed by fluorescence imaging and immunofluorescent staining. Moreover, the gastric cancer-targeting effect was verified in vivo by MRI and histology analysis. These results indicate that scFvCD44v6-PEG-g-PEI-SPION is a promising nonviral vector for gastric cancer gene therapy and diagnosis.

In vivo MR imaging tracking of transplanted mesenchymal stem cells in a rabbit model of acute peripheral nerve traction injury

To investigate in vivo MRI tracking mesenchymal stem cells (MSCs) in peripheral nerve injures using a clinically available paramagnetic contrast agent (Gd‐DTPA) and commercially available rhodamine‐incorporated transfection reagents (PEI‐FluoR).

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

Purpose To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly[N-(N′,N′-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells. Methods As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results. Results To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pKa≈6.3) groups were linked with ~50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks’ cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced. Conclusion Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors.

Intraspinal primitive neuroectodermal tumor: Imaging findings in six cases

PURPOSE To retrospectively review CT and MRI findings in a series of six intraspinal primitive neuroectoderal tumors and to find out their radiological features. METHODS CT and MRI of six patients with surgically and pathologically proved intraspinal primitive neuroectoderal tumor were retrospectively reviewed. The tumor location, morphological features, signal intensity, calcification, contrast enhancement characteristics, involvement of paraspinal soft tissues and adjacent bony structures were assessed. RESULTS Of six patients, four had extradural lesions and two had intradural, extramedullary lesions. Most lesions were well defined and manifested heterogeneous iso- or hypo-intense signal on T1-weighted imaging and hyper-intense signal on T2-weighted imaging and moderate attenuation on CT, and were heterogeneously enhanced after contrast enhancement. The lesion extending through the intervertebral foramen with a large paraspinal soft tissue mass formed was found in four patients and vertebral bone involvement was seen in four patients. CONCLUSIONS Although imaging findings are not specific of intraspinal primitive neuroectoderal tumor, this diagnosis could be suggested when MR imaging depicts an intradural, extramedullary or extradural large well-circumscribed mass which extends out from intervertebral foramen and invades paraspinal soft tissues or vertebral bones in a young patient.