Xifu Wang

The value of magnetic resonance imaging in the detection of prostate cancer in patients with previous negative biopsies and elevated prostate-specific antigen levels: a meta-analysis.

RATIONALE AND OBJECTIVES To assess the diagnostic performance of magnetic resonance imaging (MRI) for targeting prostate cancer in patients with previous negative biopsies and elevated prostate-specific antigen (PSA) levels. MATERIALS AND METHODS Pubmed, Scopus, and Cochrane Library databases were searched to identify suitable studies published from January 2001 to October 2013. Polled estimation and subgroup analysis data were obtained using a random effect model. Summary receiver operating characteristic curves were used to summarize overall test performance. RESULTS Fourteen studies involving 698 patients met the included criteria. The mean prostate cancer detection rate was 37.5%. Twelve studies had a pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of 88%, 69%, and 16.84 by patient analysis, respectively. In the subgroup analysis, magnetic resonance imaging spectroscopy (MRSI) provided higher pooled sensitivity (91%) and specificity (69%) compared with T2-weighted imaging (T2WI). MRSI combined with MRI had the highest pooled specificity (73%). By site analysis, the pooled sensitivity, specificity, and DOR in nine studies were 57%, 90%, and 14.34, respectively. In the subgroup analysis, MRSI combined with MRI showed higher pooled sensitivity (58%) and specificity (93%) compared with T2WI. Diffusion-weighted MRI (DWI) showed the highest pooled specificity: 95% but the lowest pooled sensitivity: 38%. CONCLUSIONS A limited number of studies suggest that the value of MRI to target prostate cancer in patients with previous negative biopsies and elevated PSA levels appears significant. MRI combined with MRSI is particularly accurate. Further studies are necessary to confirm the eventual role of DWI in this field.

Correlation between CT Perfusion Parameters and Microvessel Density and Vascular Endothelial Growth Factor in Adrenal Tumors

We evaluated the correlation between computed tomography (CT) perfusion parameters and markers of angiogenesis in adrenal adenomas and non-adenomas to determine if perfusion CT can be used to distinguish between them. Thirty-four patients with pathologically-confirmed adrenal tumors (17 adenomas, 17 non-adenomas) received CT perfusion imaging before surgery. CT perfusion parameters (blood flow [BF], blood volume [BV], mean transit time [MTT], and permeability surface area product [PS]) were calculated. Tumor tissue sections were examined with immunohistochemical methods for vascular endothelial growth factor (VEGF) expression and microvessel density (MVD). The mean age of the 34 patients was 43 years. The median BV was significantly higher in adenomas than in non-adenomas [12.3 ml/100 g, inter-quartile range (IQR): 10.4 to 16.5 ml/100 g vs. 8.8 ml/100 g, IQR: 3.3 to 9.4 ml/100 g, p = 0.001]. Differences in BF, MTT, and PS parameter values between adenomas and non-adenomas were not significant (p>0.05). The mean MVD was significantly higher in adenomas compared to non-adenomas (98.5±28.5 vs. 53.5±27.0, p<0.0001). Adenomas also expressed significantly higher median VEGF than non-adenomas (65%, IQR: 50 to 79% vs. 45%, IQR: 35 to 67%, p = 0.02). A moderately strong correlation between BF and VEGF (r = 0.53, p = 0.03) and between BV and MVD among adenomas (r = 0.57, p = 0.02) exist. Morphology, MVD, and VEGF expression in adenomas differ significantly from non-adenomas. Of the CT perfusion parameters examined, both BF and BV correlate with MVD, but only BF correlates with VEGF, and only in adenomas. The significant difference in BV suggests that BV may be used to differentiate adenomas from non-adenomas. However, the small difference in BV shows that it may only be possible to use BV to identify adenomas vs. non-adenomas at extreme BV values.

A comparison of 3D-CTA and 4D-CE-MRA for the dynamic monitoring of angiogenesis in a rabbit VX2 tumor.

PURPOSE To compare three-dimensional computed tomography angiography (3D-CTA) and four-dimensional contrast-enhanced magnetic resonance angiography (4D-CE-MRA) for the in vivo monitoring of tumor angiogenesis. MATERIALS AND METHODS VX2 tumors were implanted into the right thigh muscle of 30 New Zealand white rabbits. The animals were randomly assigned to 5 groups, which, respectively, were scanned by 3D-CTA and 4D-CE-MRA on day 4, 7, 10, 13, or 16 after tumor implantation. After scanning, tumors were resected and processed for conventional histology and CD-31 immunohistochemistry. Tumor volume measurements derived from CT and MR imaging were compared with histopathological data. The minimum tumor diameter and the number of new tumor blood vessels detectable by 3D-CTA and 4D-CE-MRA were also compared. RESULTS There were no significant differences in the tumor volume measurements derived from CT, MR, and histological analysis. The minimum diameter of tumor vessels detectable by 3D-CTA (0.68 ± 0.07 mm) was significantly less than that by 4D-CE-MRA (0.85 ± 0.12 mm) (P=0.005). The number of tumor vessels detected by each imaging method was not significantly different until day 13 after implantation, when 3D-CTA detected a greater number (P<0.001). The morphologic process of tumor angiogenesis was demonstrated dynamically by 3D-CTA and 4D-CE-MRA in vivo. CONCLUSIONS Tumor angiogenesis can be dynamically monitored in vivo by 3D-CTA and 4D-CE-MRA. Of the two methods, 3D-CTA has better spatial resolution, but 4D-CE-MRA allows temporal resolution of tumor angiogenesis.

Combination of vascular endothelial growth factor antisense oligonucleotide therapy and radiotherapy increases the curative effects against maxillofacial VX2 tumors in rabbits.

PURPOSE To study the effects of combination of vascular endothelial growth factor (VEGF) antisense oligonucleotide therapy and radiotherapy on maxillofacial VX2 tumors in rabbits. METHODS We used 24 New Zealand white rabbits as a model to induce maxillofacial VX2 tumor. The rabbits were randomly divided into the following 4 groups: radiotherapy group (group A), treated with 16 Gy of radiotherapy; VEGF antisense oligonucleotide treatment group (group B), treated with an injection of 150 μg of VEGF antisense oligonucleotide into the local tumor; VEGF antisense oligonucleotide combined with radiotherapy group (group C), treated with an injection of 150 μg of VEGF antisense oligonucleotide into the local tumor immediately after 16 Gy of radiotherapy; and control group (group D), treated with an injection of 300 μl 5% aqueous glucose solution into the local tumor. On days 3 and 14 after treatment, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to calculate maximal enhancement ratio (MER), slope of enhancement (SLE), and tumor volume change. Rabbits were killed on day 14 to obtain samples for pathological examination and immunohistochemical staining for VEGF. RESULTS In group C, tumor volume was significantly reduced on day 14 after treatment, and the difference was statistically different as compared to that before treatment, on day 3 after treatment and other groups (P < 0.01). Values of both MER and SLE after treatment were significantly lower than the values before treatment (P < 0.05). Pathological specimen revealed tumor cell edema, bleeding, necrosis, vascular wall thickening and occlusion, and decreased VEGF expression. The immunohistochemical score (IHS) of group C was significantly different from groups A and D respectively (P < 0.05). CONCLUSION Injecting the tumor with VEGF antisense oligonucleotide immediately after radiotherapy can enhance the curative effect on rabbit maxillofacial VX2 tumor, and DCE-MRI can serve as a reliable technique for in vivo monitoring.

Magnetic resonance imaging monitoring dual-labeled stem cells for treatment of mouse nerve injury.

BACKGROUND AIMS Adipose-derived stem cells (ADSCs) have shown great promise in the regenerative repair of injured peripheral nerves. Magnetic resonance imaging (MRI) has provided attractive advantages in tracking superparamagnetic iron oxide nanoparticle (SPION)-labeled cells and evaluating their fate after cell transplantation. This study investigated the feasibility of the use of MRI to noninvasively track ADSCs repair of peripheral nerve injury in vivo. METHODS Green fluorescent protein (GFP)-expressing ADSCs were isolated, expanded, differentiated into an SC-like phenotype (GFP-dADSCs) at early passages and subsequently labeled with SPIONs. The morphological and functional properties of the GFP-dADSCs were assessed through the use of immunohistochemistry. The intracellular stability, proliferation and viability of the labeled cells were evaluated in vitro. Through the use of a microsurgical procedure, the labeled cells were then seeded into sciatic nerve conduits in C57/BL6 mice to repair a 1-cm sciatic nerve gap. A clinical 3-T MRI was performed to investigate the GFP-dADSCs in vitro and the transplanted GFP-dADSCs inside the sciatic nerve conduits in vivo. RESULTS The GFP-dADSCs were efficiently labeled with SPIONs, without affecting their viability and proliferation. The labeled cells implanted into the mice sciatic nerve conduit exhibited a significant increase in axonal regeneration compared with the empty conduit and could be detected by MRI. Fluorescent microscopic examination, histological analysis and immunohistochemistry confirmed the axon regeneration and MRI results. CONCLUSIONS These data will elucidate the neuroplasticity of ADSCs and provide a new protocol for in vivo tracking of stem cells that are seeded to repair injured peripheral nerves.

Studies of pathology and VEGF expression in rabbit cerebrospinal fluid metastasis: application of dynamic contrast-enhanced MRI

OBJECTIVE The objective was to analyze the correlation of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with vascular endothelial growth factor (VEGF) protein expression and to assess the potential application of DCE-MRI to the rabbit cerebrospinal fluid (CSF) metastasis model. METHODS Thirty New Zealand rabbits were divided into experimental and control groups. In the experimental group, VX2 tumor cells were injected into the subarachnoid space at the plane of cisterna magna in 24 rabbits. In the control group, physiological saline was injected into the subarachnoid space at the plane of cisterna magna in six rabbits. DCE-MRI was performed at multiple time points, and several pharmacokinetic parameters, including K(trans), K(ep) and V(e), were calculated. Also, VEGF levels in plasma and CSF were evaluated by enzyme-linked immunosorbent assay prior to DCE-MRI examination. After DCE-MRI examination, the rabbits were sacrificed, and the corresponding tumor specimens were harvested. Hematoxylin-eosin staining and VEGF immunohistochemical staining were carried out, and VEGF expression in the specimens was evaluated by the immunohistochemical scoring system. RESULTS Vascular endothelial growth factor positive staining was localized in the cytoplasm and cell membranes of tumor cells, as well as in a subset of epithelial cells. Both VEGF immunohistochemical scores and VEGF expression in CSF and plasma exhibited positive correlations with K(trans) and K(ep) values as demonstrated by rank correlation statistical analysis. CONCLUSIONS Vascular endothelial growth factor expression in plasma and CSF in the CSF metastasis model was higher than in normal tissues. Therefore, DCE-MRI reliably indicated VEGF expression in the rabbit CSF metastasis model.

Irreversible electroporation in primary and metastatic hepatic malignancies: A review

Background: Liver cancer makes up a huge percentage of cancer mortality worldwide. Irreversible electroporation (IRE) is a relatively new minimally invasive nonthermal ablation technique for tumors that applies short pulses of high frequency electrical energy to irreversibly destabilize cell membrane to induce tumor cell apoptosis. Methods: This review aims to investigate the studies regarding the use of IRE treatment in liver tumors and metastases to liver. We searched PubMed for all of IRE relevant English language articles published up to September 2016. They included clinical trials, experimental studies, observational studies, and reviews. This review manuscript is nothing with ethics issues and ethical approval is not provided. Results: In recent years, increasingly more studies in both preclinical and clinical settings have been conducted to examine the safety and efficacy of this new technique, shedding light on the crucial advantages and disadvantages that IRE possesses. Unlike the current leading thermal ablation techniques, such as radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation, IRE requires shorter ablation time without damaging adjacent important vital structures. Conclusion: Although IRE has successfully claimed its valuable status in the field of hepatic cancer treatment both preclinical and clinical settings. In order to systemically test and establish its safety and efficacy for clinical applications, more studies still need to be conducted.

Chemical Shift magnetization transfer magnetic resonance imaging

The purpose of this work was to develop a chemical shift magnetization transfer (CSMT) magnetic resonance imaging (MRI) method to provide accurate magnetization transfer ratio (MTR) measurements in the presence of fat.

MRI-guided interventional natural killer cell delivery for liver tumor treatment

While natural killer (NK) cell‐based adoptive transfer immunotherapy (ATI) provides only modest clinical success in cancer patients. This study was hypothesized that MRI‐guided transcatheter intra‐hepatic arterial (IHA) infusion permits local delivery to liver tumors to improve outcomes during NK‐based ATI in a rat model of hepatocellular carcinoma (HCC). Mouse NK cells were labeled with clinically applicable iron nanocomplexes. Twenty rat HCC models were assigned to three groups: transcatheter IHA saline infusion as the control group, transcatheter IHA NK infusion group, and intravenous (IV) NK infusion group. MRI studies were performed at baseline and at 24 h, 48 h, and 8 days postinfusion. There was a significant difference in tumor R2* values between baseline and 24 h following the selective transcatheter IHA NK delivery to the tumors (P = 0.039) when compared to IV NK infusion (P = 0.803). At 8 days postinfusion, there were significant differences in tumor volumes between the control, IV, and IHA NK infusion groups (control vs. IV, P = 0.196; control vs. IHA, P < 0.001; and IV vs. IHA, P = 0.001). Moreover, there was a strong correlation between tumor R2* value change (∆R2*) at 24 h postinfusion and tumor volume change (∆volume) at 8 days in IHA group (R2 = 0.704, P < 0.001). Clinically applicable labeled NK cells with 12‐h labeling time can be tracked by MRI. Transcatheter IHA infusion improves NK cell homing efficacy and immunotherapeutic efficiency. The change in tumor R2* value 24 h postinfusion is an important early biomarker for prediction of longitudinal response.

18F-FDG PET Biomarkers Help Detect Early Metabolic Response to Irreversible Electroporation and Predict Therapeutic Outcomes in a Rat Liver Tumor Model

Purpose To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model.