Jian He

Evaluating early response of cervical cancer under concurrent chemo-radiotherapy by intravoxel incoherent motion MR imaging

BackgroundIntravoxel incoherent motion (IVIM) MR imaging has been applied in researches of various diseases, however its potential in cervical cancer patients has not been fully explored. The purpose of this study was to investigate the feasibility of IVIM MR imaging to monitor early treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancers.MethodsTwenty-one patients receiving CCRT for advanced cervical cancer were prospectively enrolled. MR examinations including IVIM imaging (with 14 b values, 0u2009~u20091000xa0s/mm2) were performed at 4 time points: 1-week prior to, 2-week and 4-week during, as well as immediately post CCRT (within 1xa0week). The apparent diffusion coefficient (ADC) maps were derived from the mono-exponential model, while the diffusion coefficient (D), perfusion fraction (f) and pseudo-diffusion coefficient (D*) maps were calculated from the bi-exponential model. Dynamic changes of ADC, D, f and D* in cervical cancers were investigated as early surrogate markers for treatment response.ResultsADC and D values increased throughout the CCRT course. Both f and D* increased in the first 2 to 3xa0weeks of CCRT and started to decrease around 4xa0weeks of CCRT. Significant increase of f value was observed from prior to CCRT (f1u2009=u20090.12u2009±u20090.52) to two-week during CCRT (f2u2009=u20090.20u2009±u20090.90, pu2009=u20090.002).ConclusionsIVIM MR imaging has the potential in monitoring early tumor response induced by CCRT in patients with cervical cancers.

Activatable Near‐Infrared Probe for Fluorescence Imaging of γ‐Glutamyl Transpeptidase in Tumor Cells and In Vivo

γ-Glutamyl transpeptidase (GGT) is a cell-membrane-bound enzyme that is involved in various physiological and pathological processes and is regarded as a potential biomarker for many malignant tumors, precise detection of which is useful for early cancer diagnosis. Herein, a new GGT-activatable near-infrared (NIR) fluorescence imaging probe (GANP) by linking of a GGT-recognitive substrate γ-glutamate (γ-Glu) and a NIR merocyanine fluorophore (mCy-Cl) with a self-immolative linker p-aminobenzyl alcohol (PABA) is reported. GANP was stable under physiological conditions, but could be efficiently activated by GGT to generate ≈100-fold enhanced fluorescence, enabling high sensitivity (detection limit of ≈3.6 mUu2009L-1 ) and specificity for the real-time imaging of GGT activity as well as rapid evaluation of the inhibition efficacy of GGT inhibitors in living tumor cells. Notably, the deep tissue penetration ability of NIR fluorescence could further allow GANP to image GGT in frozen tumor tissue slices with large penetration depth (>100u2005μm) and in xenograft tumors in living mice. This GGT activatable NIR fluorescence imaging probe could facilitate the study and diagnosis of other GGT-correlated diseases in vivo.

Tumor-targeting CuS nanoparticles for multimodal imaging and guided photothermal therapy of lymph node metastasis

Precise diagnosis of lymph node metastasis to guide lymphadenectomy is highly important for gastric cancer therapy in clinics. Though surgical dissection of regional metastatic lymph nodes remains the only way for gastric cancer therapy, the extended dissection may cause unavoidable postoperative risk of complications. It is still lack of effective method enabling the accurate removal of metastatic gastric cancer cells in lymph nodes with minimum injuries to normal tissue. Herein, we report a new fluorescent copper sulfide (CuS) nanoparticle (RGD-CuS-Cy5.5) enabling both non-invasive multimodality imaging and targeting photothermal therapy (PTT) of metastatic gastric cancer cells in lymph nodes. We demonstrate that RGD-CuS-Cy5.5 can easily drain into sentinel lymph nodes (SLN) after injection into primary tumors, and selectively enter into metastatic gastric MNK45 tumor cells via αvβ3 integrin-mediated endocytosis. The resulting strong near-infrared (NIR) fluorescence and computed tomography (CT) contrast in metastatic SLN compared to normal SLN can precisely differentiate SLN metastasis of gastric cancers. Guided by the imaging, localized PTT with RGD-CuS-Cy5.5 is conducted upon irradiation with an 808u202fnm laser, resulting in complete removal of metastatic gastric tumor cells in SLN without obvious toxicity. Moreover, RGD-CuS-Cy5.5 can also allow for the rapid and non-invasive self-monitoring of PTT efficacy against metastatic SLNs in living mice. This study highlights the potential of using RGD-CuS-Cy5.5 for imaging-guided and targeting PTT of SLN metastasis in vivo, which may be applicable for the metastatic gastric cancer therapy in clinics.nnnSTATEMENT OF SIGNIFICANCEnRGD-CuS-Cy5.5 nanoparticles possess NIR fluorescence and CT signals for in vivo bimodality imaging of lymph node metastasis. Strong photothermal property under irradiation at 808u202fnm for efficient PTT. Easy drain into sentinel lymph nodes and selective enter metastatic gastric cancer cells via αvβ3 integrin-mediated endocytosis. Rapid and non-invasive monitoring of therapeutic efficacy against lymph node metastasis.

Tuning the electrical transport of type II Weyl semimetal WTe 2 nanodevices by Ga+ ion implantation

Here we introduce lattice defects in WTe2 by Ga+ implantation (GI), and study the effects of defects on the transport properties and electronic structures of the samples. Theoretical calculation shows that Te Frenkel defects is the dominant defect type, and Raman characterization results agree with this. Electrical transport measurements show that, after GI, significant changes are observed in magnetoresistance and Hall resistance. The classical two-band model analysis shows that both electron and hole concentration are significantly reduced. According to the calculated results, ion implantation leads to significant changes in the band structure and the Fermi surface of the WTe2. Our results indicate that defect engineering is an effective route of controlling the electronic properties of WTe2 devices.

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased (P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease (P = 0.022), and SD, 75th and 90th percentiles continued to increase (P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADCmean, ADCmin, kurtosis, and 25th, 50th, 75th, 90th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADCmax could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 (P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy.

Apparent diffusion coefficient histogram shape analysis for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy

BackgroundTo explore the role of apparent diffusion coefficient (ADC) histogram shape related parameters in early assessment of treatment response during the concurrent chemo-radiotherapy (CCRT) course of advanced cervical cancers.MethodsThis prospective study was approved by the local ethics committee and informed consent was obtained from all patients. Thirty-two patients with advanced cervical squamous cell carcinomas underwent diffusion weighted magnetic resonance imaging (b values, 0 and 800xa0s/mm2) before CCRT, at the end of 2nd and 4th week during CCRT and immediately after CCRT completion. Whole lesion ADC histogram analysis generated several histogram shape related parameters including skewness, kurtosis, s-sDav, width, standard deviation, as well as first-order entropy and second-order entropies. The averaged ADC histograms of 32 patients were generated to visually observe dynamic changes of the histogram shape following CCRT.ResultsAll parameters except width and standard deviation showed significant changes during CCRT (all Pu2009<u20090.05), and their variation trends fell into four different patterns. Skewness and kurtosis both showed high early decline rate (43.10xa0%, 48.29xa0%) at the end of 2nd week of CCRT. All entropies kept decreasing significantly since 2xa0weeks after CCRT initiated. The shape of averaged ADC histogram also changed obviously following CCRT.ConclusionsADC histogram shape analysis held the potential in monitoring early tumor response in patients with advanced cervical cancers undergoing CCRT.

Whole-lesion ADC histogram and texture analysis in predicting recurrence of cervical cancer treated with CCRT

Purpose To explore the value of whole-lesion apparent diffusion coefficient (ADC) histogram and texture analysis in predicting tumor recurrence of advanced cervical cancer treated with concurrent chemo-radiotherapy (CCRT). Methods 36 women with pathologically confirmed advanced cervical squamous carcinomas were enrolled in this prospective study. 3.0 T pelvic MR examinations including diffusion weighted imaging (b = 0, 800 s/mm2) were performed before CCRT (pre-CCRT) and at the end of 2nd week of CCRT (mid-CCRT). ADC histogram and texture features were derived from the whole volume of cervical cancers. Results With a mean follow-up of 25 months (range, 11 ∼ 43), 10/36 (27.8%) patients ended with recurrence. Pre-CCRT 75th, 90th, correlation, autocorrelation and mid-CCRT ADCmean, 10th, 25th, 50th, 75th, 90th, autocorrelation can effectively differentiate the recurrence from nonrecurrence group with area under the curve ranging from 0.742 to 0.850 (P values range, 0.001 ∼ 0.038). Conclusions Pre- and mid-treatment whole-lesion ADC histogram and texture analysis hold great potential in predicting tumor recurrence of advanced cervical cancer treated with CCRT.

Role of intravoxel incoherent motion MR imaging in preoperative assessing HER2 status of gastric cancers

Purpose To explore the role of intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging in evaluating human epidermal growth factor receptor 2 (HER2) status of gastric cancers preoperatively. Results The apparent diffusion coefficient (ADC) and pure diffusion coefficient (D) values correlated positively with HER2 scores of gastric cancers significantly (r = 0.276, P = 0.048; r = 0.481, P < 0.001, respectively). The ADC and D values of HER2 positive gastric cancers were significantly higher than those of HER2 negative tumors (P = 0.033, 0.007, respectively). With a cut-off value of 1.321 and 1.123 × 10−3 mm2/sec, the ADC and D values could distinguish HER2 positive gastric cancers from HER2 negative ones with an area under the curve of 0.733 and 0.762, respectively (P = 0.023, 0.011, respectively). Materials and methods Fifty-three patients with gastric cancers underwent IVIM MR imaging preoperatively. The values of ADC, D, pseudo diffusion coefficient (D*) and perfusion related fraction (f) of the lesions were obtained. Partial correlation test including tumor volume was performed to analyze correlations between IVIM values and HER2 scores excluding the impact of tumor size. IVIM parameters of gastric cancers with different HER2 status were compared using independent samples t test. Diagnostic performance of IVIM parameters in distinguishing HER2 positive gastric cancers from negative ones was tested with receiver operating characteristic analysis. Conclusions We confirmed the feasibility of IVIM MR imaging in preoperative assessment of HER2 status of gastric cancers, which might make up the shortfall of biopsy and facilitate personalized treatment for patients with gastric cancers.

Value of whole-lesion apparent diffusion coefficient (ADC) first-order statistics and texture features in clinical staging of cervical cancers

AIMnTo explore the value of whole-lesion apparent diffusion coefficient (ADC) first-order statistics and texture features in clinical staging of cervical cancers.nnnMATERIALS AND METHODSnFifty-six women (mean age, 51 years) with histopathologically confirmed cervical cancers underwent 3xa0T pelvic magnetic resonance imaging including diffusion-weighted imaging (b=0, 800xa0s/mm2) prospectively. The ADC first-order statistics and texture features derived from the whole volume of cervical cancers were correlated with International Federation of Gynecology and Obstetrics (FIGO) stages (i.e., stages I, II, III, and IV).nnnRESULTSnThe first-order statistics of skewness, kurtosis, and entropy, and the texture features of entropy(H) and homogeneity correlated positively, while the texture feature of energy correlated negatively with FIGO stages (all p<0.05). Skewness, kurtosis, entropy, entropy(H), and homogeneity were significantly higher, while energy was significantly lower in cervical cancers at higher (IIB-IVA) than lower (IB-IIA) FIGO stages (all p<0.05). Kurtosis and energy had the largest areas under the receiver operating characteristic (ROC) curve of 0.749 and 0.746 in differentiating cervical cancers at lower (IB-IIA) from higher (IIB-IVA) FIGO stages.nnnCONCLUSIONnWhole-lesion ADC first-order statistics and texture features proved relevant and meaningful in the clinical staging of cervical cancers.

Texture analysis of CT images in predicting malignancy risk of gastrointestinal stromal tumours.

AIMnTo explore the role of texture analysis of computed tomography (CT) images in predicting the malignancy risk of gastrointestinal stromal tumours (GISTs).nnnMATERIALS AND METHODSnSeventy-eight patients with histopathologically confirmed GISTs underwent preoperative CT. Texture analysis was performed on unenhanced and contrast-enhanced CT images, respectively. Fourteen CT texture parameters were obtained and compared among GISTs at different malignancy risks with one-way analysis of variance or independent-samples Kruskal-Wallis test. Correlations between CT texture parameters and malignancy risk were analysed with Spearmans correlation test. Diagnostic performance of CT texture parameters in differentiating GISTs at low/very low malignancy risk was tested with receiver operating characteristic (ROC) analysis.nnnRESULTSnThree parameters on unenhanced images (r=-0.268-0.506), four parameters on arterial phase (r=-0.365-0.508), and six parameters on venous phase (r=-0.343-0.481) imaging correlated significantly with malignancy risk of GISTs, respectively (all p<0.05). For identifying GISTs at low/very low malignancy risk, three parameters on unenhanced images (area under ROC curve [AUC], 0.676-0.802), four parameters on arterial phase (AUC, 0.637-0.811), and six parameters on venous phase (AUC, 0.636-0.791) imaging showed significant diagnostic performance, respectively (all p<0.05), especially maximum frequency on both unenhanced and contrast-enhanced images (AUC, 0.791-0.811).nnnCONCLUSIONnTexture analysis of CT images holds great potential to predict the malignancy risk of GISTs preoperatively.