IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer.

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. METHODS: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. RESULTS: In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3-61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010). CONCLUSIONS: Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer. TRIAL REGISTRATION: NCT04766320, Jan 04, 2021.

Combined MRI-TRUS fusion targeted and systematic biopsy versus systematic biopsy alone for the detection of prostate cancer: protocol for a prospective single-centre trial.

INTRODUCTION: The classic way of diagnosing prostate cancer (PCa) is by conducting the 12-core systematic biopsy (SB). However, it has a low detection rate for clinically significant PCa (csPCa) and can lead to the detection of clinically insignificant PCa (cisPCa). Although MRI-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TB) can effectively improve the detection rate of csPCa, it may still miss some cases. Therefore, we propose using a combination of TB and SB methods to enhance the detection rate of csPCa while minimising the detection rate of cisPCa. METHODS AND ANALYSIS: This study is a prospective, single-centre investigation that aims to assess and compare the detection rate of csPCa using MRI-TRUS fusion TB combined with SB versus TRUS 12-core SB alone. Biopsy-naïve men with suspected PCa will be subjected to multiparametric MRI. Patients with Prostate Imaging Reporting and Data System (V.2.1) score ≥3 will be enrolled in the TB-SB combination group. The sample size is established as 660 participants, considering a 10% drop-out rate. The primary outcome is the detection rate of csPCa in men without prior biopsy using MRI-TRUS fusion TB combined with the standard TRUS-guided 12-core SB method. CsPCa will be defined as International Society of Urological Pathology Grade ≥2. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee at the Shanghai Tenth People's Hospital, an affiliated hospital of Tongji University School of Medicine. The research results will be published in a peer-reviewed international journal. TRIAL REGISTRATION NUMBER: ChiCTR2000036089.

Concordance and Clinical Significance of Genomic Alterations in Progressive Tumor Tissue and Matched Circulating Tumor DNA in Aggressive-variant Prostate Cancer.

Sequencing of circulating tumor DNA (ctDNA) is a minimally invasive approach to reveal the genomic alterations of cancer; however, its comparison with sequencing of tumor tissue has not been well documented in real-world patients with aggressive-variant prostate cancer (AVPC). Concordance of genomic alterations was assessed between progressive tumor tissue and matched ctDNA by next-generation sequencing for 63 patients with AVPC. Associations of genomic alterations with progression-free survival (PFS) and overall survival (OS) were investigated using Kaplan-Meier and Cox regression analyses. A total of 161 somatic mutations (SMs) and 84 copy-number variants (CNVs) were detected in tumors, of which 97 were also found in ctDNA, giving concordance of 39.6% (97/245) across all SMs and CNVs, 49.7% for SMs only and 20.2% for CNVs only. Across all patients with AVPC, chemotherapy was associated with significantly longer median PFS (6 vs. 0.75 months, P = 0.001) and OS (11 vs. 8 months, P < 0.001) than next-generation hormonal therapy (NHT). Among types of chemotherapy, additional platinum-based chemotherapy was associated with significantly longer median PFS and OS than docetaxel only in patients with TP53, RB1, or PTEN alterations, and in those with ctDNA% ≥ 13.5%. The concordance analysis first provides evidence for combining the sequencing of ctDNA and tumor tissue in real-world patients with AVPC. Chemotherapy is associated with significantly better survival than NHT, and the benefit of additional platinum-based chemotherapy may depend on the presence of alterations in TP53, RB1, or PTEN and on a sufficiently high proportion of ctDNA in patients with AVPC. SIGNIFICANCE: AVPC is a highly malignant and heterogeneous disease. Sequencing of ctDNA is a minimally invasive approach to reveal genomic alterations. On the basis of the current real-world study, we found ctDNA does not fully recapitulate the landscape of genomic alterations from progressive tumor tissue in AVPC. We also revealed AVPC can benefit from chemotherapy, especially platinum-based regimens. TP53/RB1/PTEN alterations in ctDNA or tumor tissue could be biomarkers for platinum-based chemotherapy in this setting.

Influence of a new motion correction algorithm (CardioCapture) on the correlation between heart rate and optimal reconstruction phase.

Purpose: To investigate the effect of a new motion correction algorithm (CardioCapture) on the correlation between heart rate and optimal reconstruction phase by evaluating the impact of wide detector CT combined with CardioCapture on CCTA image quality. Materials and methods: All cases were examined from April 2021 to September 2021. Two experienced radiologists scored these images on a four-point Likert scale. First, all images were divided into eight groups according to HR (at an interval of 5 bpm). The subjective score of images, the frequency of used CardioCapture, and the proportion of the diastolic reconstruction phase were compared in each group. Then, all cases were divided into two groups, one group was reconstructed using the automatic temporal reconstruction algorithm (Ephase) only, and the other group was reconstructed using the Ephase with the CardioCapture. The relationship between HR and the diastolic reconstruction phase was analyzed by the receiver operator characteristic curve (ROC). Result: The data of 515 patients were studied. With the increase in HR, the subjective image score decreased, the frequency of CardioCapture increased, and the phase ratio of diastolic reconstruction decreased. When the HR was less than 70 bpm, the percentage of excellence image in each group surpassed 94.90%. The highest utilization rate of CardioCapture was 65.22%, and the lowest proportion of diastolic reconstruction was 72.46%. When 70 bpm < HR ≤ 75 bpm, the image excellence rate was 90.43%, the CardioCapture utilization rate was 82.05%, and the diastolic reconstruction rate was 56.41%.When 75 bpm < HR ≤ 80 bpm, the image excellence rate was 87.91%, the CardioCapture utilization rate was 80.65%, and the diastolic reconstruction was 6.45%.When the HR > 80 bpm, the image excellence rate was 80.00%, the CardioCapture utilization rate was 75.00%, and the diastolic reconstruction rate was 22.50%. The best cut-off point between HR and the diastolic reconstruction ROC curve in the groups without CardioCapture was 65 bpm, while that in groups with CardioCapture was 68 bpm. Conclusion: The CardioCapture can effectively improve the image quality of CCTA with high HR. By maintaining the HR below 68 bpm and utilizing the prospective ECG-gated narrow phase axial scan, it is possible to ensure optimal image quality and concurrently reduce radiation dose.

Intravoxel incoherent motion diffusion-weighted imaging in quantitative evaluation of Ileal Crohn's disease - A comparison with dynamic contrast-enhanced magnetic resonance imaging and ileocolonoscopy.

OBJECTIVES: To investigate the prospective role of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in evaluating terminal ileal Crohn's disease (CD) inflammation quantitatively, compared with quantitative dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) and ileocolonoscopic segmental score. METHODS: Fifty CD patients underwent magnetic resonance enterography (MRE) including IVIM-DWI and quantitative DCE-MRI from Jan. 2017 to Nov. 2019. ADC, D, D* and f value of IVIM-DWI and Ktrans, Kep, and Ve value of DCE-MRI in normal (n = 50) and inflamed bowel segments (n = 50), defined during the clinical MRI analysis, were calculated and compared using Wilcoxon signed-rank tests respectively. Receiver operating characteristic (ROC) analysis was performed. Correlations between IVIM-DWI and DCE-MRI parameters in comparison with ileocolonoscopic segmental score were assessed using Spearman's rank correlation analysis. RESULTS: For IVIM-DWI, ADC, D, D* and f value showed significant differences respectively between normal and inflamed bowel segments (p < 0.05). ADC value presented the highest diagnostic accuracy (AUC = 0.813) and sensitivity (92%), and D value presented the highest specificity (84%) for the evaluation of inflamed bowel segments. For DCE-MRI, Ktrans value presented the highest diagnostic accuracy (AUC = 0.835), the highest sensitivity for Kep value (88%) and the highest specificity for Ve value (96%). ADC, f and Ktrans value had high correlations with ileocolonoscopic score respectively (r = -0.739-0.876, p < 0.01). The logarithm of normalized signal intensity/b-values for IVIM-DWI could also indicate directly the evident difference between the normal and inflamed bowel segments of terminal ileal CD. CONCLUSION: IVIM-DWI will be another promising noninvasive tool to provide precise quantitative-indicators in evaluating inflamed bowel segments of terminal ileal CD with little contrast-agent damage worries.

Transrectal ultrasound examination of prostate cancer guided by fusion imaging of multiparametric MRI and TRUS: avoiding unnecessary mpMRI-guided targeted biopsy.

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.

Cross-Modal Prostate Cancer Segmentation via Self-Attention Distillation.

The automatic and accurate segmentation of the prostate cancer from the multi-modal magnetic resonance images is of prime importance for the disease assessment and follow-up treatment plan. However, how to use the multi-modal image features more efficiently is still a challenging problem in the field of medical image segmentation. In this paper, we develop a cross-modal self-attention distillation network by fully exploiting the encoded information of the intermediate layers from different modalities, and the generated attention maps of different modalities enable the model to transfer significant and discriminative information that contains more details. Moreover, a novel spatial correlated feature fusion module is further employed for learning more complementary correlation and non-linear information of different modality images. We evaluate our model in five-fold cross-validation on 358 MRI images with biopsy confirmed. Without bells and whistles, our proposed network achieves state-of-the-art performance on extensive experiments.

Higher liver stiffness in patients with chronic congestive heart failure: data from NHANES with liver ultrasound transient elastography.

BACKGROUND: Liver stiffness in patients with chronic congestive heart failure (CCHF) is poorly understood and liver ultrasound transient elastography (LUTE) is a new non-invasive method to detect this condition. In this cross-sectional study we explored liver stiffness and secondary congestive hepatopathy in patients with CCHF detected by LUTE. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES 2017-2018) were analyzed. All participants undergoing LUTE and without liver disease were included, among whom, 110 participants were diagnosed with CCHF. The cut-off values of stiffness for fibrosis and cirrhosis were above 7.65 and 13.01 kPa, respectively. Data regarding liver stiffness were compared between the participants with and without CCHF. RESULTS: Among patients with CCHF, the median liver stiffness was 6.0 kPa, above 7.65 kPa in 32.7% of patients, and above 13.01 kPa in 14.6% of patients. The mean liver stiffness was 5.0 kPa in the control group and was significantly lower than that of patients with CCHF (P<0.001). The ratio of serum albumin/globulin (A/G) gradually decreased according to the liver stiffness of patients with CCHF (P=0.03). CONCLUSIONS: Patients with CCHF had higher liver stiffness values than controls, nearly one-third had substantial fibrosis, and more than one in seven patients progressed to cirrhosis. The A/G ratio may be a potential biomarker for liver stiffness caused by CCHF.

Crohn's disease exacerbated by IL-17 inhibitors in patients with psoriasis: a case report.

BACKGROUND: Previous studied revealed that psoriasis and Inflammatory bowel disease (IBD) have highly overlapping epidemiological characteristics, genetic susceptibility loci, disease risk factors, immune mechanisms, and comorbidities. More and more biologics have been used to treat psoriasis and IBD. Interleukin (IL)-17 inhibitors played an important role in the treatment of psoriasis, but induced and aggravated inflammatory bowel disease in some patients. IL-23 inhibitors have shown to be effective to both psoriasis and CD. CASE PRESENTATION: Forty-one year old Chinese male patient who came to the hospital for psoriasis, developed severe gastrointestinal symptoms after using an IL-17 inhibitor, and was diagnosed with Crohn's disease (CD). The patient eventually used an IL-23 inhibitor to relieve both psoriasis and CD. CONCLUSION: IBD patients and psoriasis patients have increased probability of suffering from the other disease. The case that patients had suffered from psoriasis and CD before the use of IL-17 inhibitor is quite rare. This case suggests that physicians need to be careful when treating patients with psoriasis and CD with biologics, and it is necessary to evaluate the gastrointestinal tract.

Beneficial Effects of Glycyrrhizin in Chronic Periodontitis Through the Inhibition of Inflammatory Response.

Elevated inflammatory cytokines and high mobility group box 1 (HMGB1) production are associated with chronic periodontitis (CP). Glycyrrhizin is the major constituent of Glycyrrhiza glabra. L. (Fabaceae) root with anti-inflammation activities. This study evaluated the effects of glycyrrhizin on CP. TNF-α-treated human periodontal ligament stem cell (hPDLSC) model was established, and was administrated with 1, 2 or 5 mM glycyrrhizin for 24 h. After treatment, the expression of HMGB1and inflammatory cytokines was monitored. Significantly increased HMGB1 (median: 5646.4, range: 1918.2-8233.7 vs median: 204.5, range: 98.7-283.6, pg/mL), TNF-α (median: 345.5, range: 161.0-567.9 vs median: 93.5, range: 58.1-159.3, pg/mL), IL-1ß (median: 2014.6, range: 209.5-4308.1 vs median: 224.5, range: 48.8-335.8, pg/mL) and IL-6 (median: 1223.6, range: 398.2-2183.8 vs median: 240.4, range: 105.2-400.5, pg/mL) were detected in gingival crevicular fluid from CP patients. Glycyrrhizin significantly prevented TNF-α-induced expression of HMGB1 (691.5 ± 136.4 vs 142.8 ± 57.3 pg/mL), IL-6 (388.1 ± 85.2 vs 189.4 ± 61.2 pg/mL) and IL-1ß (176.3 ± 47.2 vs 53.9 ± 25.7 pg/mL) in hPDLSC. In CP rats, glycyrrhizin significantly decreased HMGB1 (5795.6 ± 1121.5 vs 586.4 ± 436.8 pg/mL), TNF-α (421.8 ± 93.7 vs 87.9 ± 21.6 pg/mL), IL-6 (1423.8 ± 235.2 vs 622.6 ± 176.1 pg/mL) and IL-1ß (1562.8 ± 334.3 vs 733.5 ± 265.1 pg/mL) in gingival crevicular fluid. Glycyrrhizin suppresses inflammatory activities in CP rats and represents a promising molecule for controlling CP.

Contrast-enhanced magnetic resonance (MR) T1 mapping with low-dose gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) is promising in identifying clear cell renal cell carcinoma histopathological grade and differentiating fat-poor angiomyolipoma.

BACKGROUND: This study aimed to identify clear cell renal cell carcinoma (ccRCC) histopathological grade and differentiate it from fat-poor angiomyolipoma (AML). This was achieved through contrast-enhanced magnetic resonance (MR) T1 mapping with intravenous low-dose gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). METHODS: In total, 56 consecutive patients received MR scanning between January 2016 and December 2018 using the pre- and post- contrast-enhanced T1 mapping sequences with low-dose Gd-DTPA (0.036 mmol/kg). RCCs were pathologically proven in 40 patients after surgery and graded according to the International Society of Urological Pathology (ISUP) classification system. Ten AMLs were pathologically proven by surgery histopathology and six AMLs were diagnosed by magnetic resonance imaging (MRI). Patients were followed up for more than half a year. The mean T1 values of the renal lesion and ipsilateral normal renal parenchyma were measured before and after Gd-DTPA administration (T1p and T1e). The reduction of T1 value (T1d) and the ratio of its reduction (T1d %) were calculated and compared. RESULTS: In 40 ccRCCs, higher-grade [International Society of Urologic Pathology (ISUP) grade 3 and 4] and lower-grade (ISUP grade 1 and 2) ccRCCs were noted in 13 and 27 patients, respectively. The mean T1p was 1,514.8±139.4 ms and the mean T1d was 907.7±193.7 ms in the higher-grade ccRCCs, which were significantly higher than in the lower-grade ccRCCs (T1p =1,251.7±151.5 ms and T1d =648.5±218.2 ms, respectively; P<0.001). Fat-poor AMLs had higher T1p (1,677.3±104.8 ms) and T1e (865.6±251.5 ms) as compared to ccRCCs (P<0.001). Combined T1p + T1d showed the highest area under the curve (AUC) (0.912) in the differentiation of higher-grade ccRCCs from lower-grade ccRCCs (P=0.010). Combined T1p + T1e had the highest AUC (0.956) in the differentiation between ccRCCs and fat-poor AMLs (P=0.010). All T1 mapping metrics could discriminate between normal renal parenchyma and renal lesions (P<0.001). No significant difference was found in the T1p and T1e at different parts of the ipsilateral normal renal parenchyma. Interobserver agreement for quantitative longitudinal relaxation time in the T1 maps was excellent. CONCLUSIONS: Contrast-enhanced T1 mapping with low-dose Gd-DTPA may provide a more reliable and accurate approach in identifying ccRCCs histopathological grade and differentiating ccRCCs from fat-poor AMLs.

The efficacy of added shear wave elastography (SWE) in breast screening for women with inconsistent mammography and conventional ultrasounds (US).

PURPOSE: To evaluate the efficacy of added shear wave elastography (SWE) in breast screening for women with results inconsistent between mammography and conventional ultrasounds (US). MATERIALS AND METHODS: The study consisted of 282 pathologically proven breast lesions. The cancer probability from screening by mammography and conventional US were scored using Breast Imaging Reporting and Data System (BI-RADS). Elastography was used to re-evaluate inconsistent conventional US and mammography results. The diagnostic performance of conventional US, mammography, and Combined conventional clinical imaging and SWE was compared. The clinicopathological features of all breast cancer patients with inconsistent (and consistent) conventional US and mammography findings were compared. RESULT: Finally, 147 lesions were confirmed benign and 135 were malignant. The AUC of Combined conventional clinical imaging plus elastography imaging (0.870) was significantly higher than mammography (0.735, p < 0.001) or conventional US (0.717, p < 0.001) alone. Among the 135 breast cancers, 79 of the conventional US and mammography findings were consistent and 56 were inconsistent. Younger age(<50y) (p = 0.035), non-invasive (p = 0.037), smaller size (p = 0.002) and negative lymph node status (p = 0.026) were significantly associated with inconsistent findings. CONCLUSION: The added SWE in breast screening when inconsistent results from mammography and conventional US occurred is necessary and effective.

Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats.

BACKGROUND: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. METHODS: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. RESULTS: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels. CONCLUSIONS: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.

Comparative analysis of MDCT and MRI in diagnosing chronic gallstone perforation and ileus.

OBJECT: To evaluate MDCT and MRI in identifying chronic gallstone perforation (GSP) and ileus, even the risk factors prior to perforation. METHODS: Twenty-three cases of gallstone ileus (GSI) and three cases of calculus gallbladder-choledochus perforation were scanned by MDCT before treatment. Meanwhile, twelve patients received two-view abdominal X-ray film and eight patients received MRI examination. All images were analyzed respectively and blindly to the results of surgery or interventional endoscopy, besides five cases of MDCT and one case of MRI images scanned before GSP were analyzed comparatively. RESULTS: MDCT could identify 100.0% of intestinal obstruction and pneumobilia of GSI, it had not statistical difference with abdominal X-ray film. But MDCT could differenciate and precisely locate 88.5% of the ectopic stone, higher than that of abdominal X-ray film (50%), p value ˂ 0.05, moreover it presented cholecystitis, edema or discontinuous walls of gallbladder and intestine and bilio-enteral fistula (26.9%). MRI and MRCP could precisely visualize the fistula (100%) and the ruptured bile duct. Abnormal edema or thin gallbladder wall, large stone size (> 2 cm) and incarceration in the neck of gallbladder, the blurring fat line between gallbladder and duodenum were considered main risk signs prior to GSP. CONCLUSION: MDCT is being considered as an effective and reliable technique to identify GSP and GSI early, however MRI and MRCP will aid to differentiate the complex GSP. It will be a considerable prospective for MDCT and MRI to estimate the risk factors prior to gallbladder perforation.

Measurement of single-kidney glomerular filtration function from magnetic resonance perfusion renography.

Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidney, and is considered to be the reference standard in the evaluation of renal function. There are many ways to test the GFR clinically, such as serum creatinine concentration, blood urea nitrogen and SPECT renography, however, they're all not a good standard to evaluate the early damage of renal function. In recent years, the improvement of MRI hardware and software makes it possible to reveal physiological characteristics such as renal blood flow or GFR by dynamic contrast enhancement magnetic resonance perfusion renography (DEC MRPR). MRPR is a method used to monitor the transit of contrast material, typically a gadolinium chelate, through the renal cortex, the medulla, and the collecting system. This review outlines the basics of DCE MRPR included acquisition of dynamic MR perfusion imaging, calculation of the contrast concentration from signal intensity and compartment models, and some challenges of MRPR method faced in prospective clinical application.

Renalase protects against contrast-induced nephropathy in Sprague-Dawley rats.

BACKGROUND: Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure. Oxidative stress, apoptosis and inflammation play crucial roles in CIN. Renalase is a newly discovered monoamine oxidase from the kidney. We hypothesize that renalase could protect against CIN through anti-oxidation, anti-inflammation and anti-apoptosis pathways. METHODS: We tested our hypothesis in vivo with a rat model of Ioversol-induced CIN and in vitro. Sprague-Dawley rats were divided into 4 groups (n = 6 per group): control group, Ioversol group (rats subjected to Ioversol-induced CIN), Ioversol plus vehicle group (CIN rats pretreated with vehicle) and Ioversol plus renalase group (CIN rats pretreated with 2 mg/kg recombinant renalase). HK2 cells were treated with Ioversol or H2O2. RESULTS: The results showed that pretreatment with renalase attenuated the deterioration of renal function, tubular necrosis, oxidative stress, apoptosis and inflammation (P<0.05). Furthermore, renalase protected HK2 cells against the cytotoxicity of Ioversol and suppressed Caspase-3 activity, oxidative stress and apoptosis induced by H2O2. CONCLUSION: Recombinant renalase protected CIN in rats through anti-oxidation, anti-apoptosis and anti-inflammation mechanisms.

Cone beam breast CT with multiplanar and three dimensional visualization in differentiating breast masses compared with mammography.

OBJECTIVE: This pilot study was to evaluate cone beam breast computed tomography (CBBCT) with multiplanar and three dimensional (3D) visualization in differentiating breast masses in comparison with two-view mammograms. METHODS: Sixty-five consecutive female patients (67 breasts) were scanned by CBBCT after conventional two-view mammography (Hologic, Motarget, compression factor 0.8). For CBBCT imaging, three hundred (1024 × 768 × 16b) two-dimensional (2D) projection images were acquired by rotating the x-ray tube and a flat panel detector (FPD) 360 degree around one breast. Three-dimensional CBBCT images were reconstructed from the 2D projections. Visage CS 3.0 and Amira 5.2.2 were used to visualize reconstructed CBBCT images. RESULTS: Eighty-five breast masses in this study were evaluated and categorized under the breast imaging reporting and data system (BI-RADS) according to plain CBBCT images and two-view mammograms, respectively, prior to biopsy. BI-RADS category of each breast was compared with biopsy histopathology. The results showed that CBBCT with multiplanar and 3D visualization would be helpful to identify the margin and characteristics of breast masses. The category variance ratios for CBBCT under the BI-RADS were 23.5% for malignant tumors (MTs) and 27.3% for benign lesions in comparison with pathology, which were evidently closer to the histopathology results than those of two-view mammograms, p value <0.01. With the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) of CBBCT was 0.911, larger than that (AUC 0.827) of two-view mammograms, p value <0.01. CONCLUSION: CBBCT will be a distinctive noninvasive technology in differentiating and categorizing breast masses under BI-RADS. CBBCT may be considerably more effective to identify breast masses, especially some small, uncertain or multifocal masses than conventional two-view mammography.

Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles.

Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS). Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 µM) and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.

Quantification of pancreatic exocrine function of chronic pancreatitis with secretin-enhanced MRCP.

AIM: To obtain reference values for pancreatic flow output rate (PFR) and peak time (PT) in healthy volunteers and chronic pancreatitis (CP); to correlate quantification of secretin enhanced magnetic resonance cholangiopancreatography (SMRCP) of pancreatic fluid output following secretin with fecal elastase-1 (FE-1) tests. METHODS: The present study includes 53 subjects comprised of 17 healthy individuals and 36 patients with CP from April 2011 to January 2013. The 36 patients with CP were divided into three groups of mild CP (n = 14), moderate CP (n = 19) and advanced CP (n = 3) by M-ANNHEIM classification for CP.. Fifty-three cases underwent FE-1 test and magnetic resonance imaging using 3.0 T-device (Signa EXCITE, GE Healthcare). Coronal T2-weighted single-shot turbo spin-echo, spiratory triggered, covering the papillae, duodenum and small bowel. MRCP was performed with a heavily T2-weighted fat-suppressed long TE HASTE sequence (thick slab 2D MRCP sequence), repeated every 2 min up to 11 min after 0.1 mL/kg secretin injection (Secrelux, Sanochemia(®), Germany). FE-1 test used sandwich enzyme-linked immunosorbent assay (ELISA) test (ScheBo. Tech(®), Germany). RESULTS: A good linear correlation showed between the calculated volume and the actual volume by Phantom experiments. Fifty-three paired Quantification of secretin enhanced magnetic resonance cholangiopancreatography (MRCPQ) and FE-1 data sets were analyzed. The mean FE-1 of 53 cases was 525.41 ± 94.44 µg/g for 17 healthy volunteers, 464.95 ± 136.13 µg/g for mild CP, 301.55 ± 181.55 µg/g for moderate CP, 229.30 ± 146.60 µg/g for advanced CP. Also, there was statistically significant difference in FE-1 (P = 0.0001) between health and CP. The mean values of PFR and PT were 8.18 ± 1.11 mL/min, 5.76 ± 1.71 min for normal; 7.27 ± 2.04 mL/min, 7.71 ± 2.55 min for mild CP; 4.98 ± 2.57 mL/min, 9.10 ± 3.00 min for moderate CP; 4.13 ± 1.83 mL/min, 12.33 ± 1.55 min for advanced CP. Further, statistically significant difference in PFR (P = 0.0001) and PT (P = 0.0001) was observed between health and CP. Besides, there was correlation (r = 0.79) and consistency (K = 0.6) between MRCPQ and ELISA Test. It was related between M-ANNHEIM classification and PFR (r = 0.55), FE-1 (r = 0.57). CONCLUSION: SMRCP can provide a safe, non-invasive and efficient method to evaluate the exocrine function of the pancreas.

Dynamic cone beam CT angiography of carotid and cerebral arteries using canine model.

PURPOSE: This research is designed to develop and evaluate a flat-panel detector-based dynamic cone beam CT system for dynamic angiography imaging, which is able to provide both dynamic functional information and dynamic anatomic information from one multirevolution cone beam CT scan. METHODS: A dynamic cone beam CT scan acquired projections over four revolutions within a time window of 40 s after contrast agent injection through a femoral vein to cover the entire wash-in and wash-out phases. A dynamic cone beam CT reconstruction algorithm was utilized and a novel recovery method was developed to correct the time-enhancement curve of contrast flow. From the same data set, both projection-based subtraction and reconstruction-based subtraction approaches were utilized and compared to remove the background tissues and visualize the 3D vascular structure to provide the dynamic anatomic information. RESULTS: Through computer simulations, the new recovery algorithm for dynamic time-enhancement curves was optimized and showed excellent accuracy to recover the actual contrast flow. Canine model experiments also indicated that the recovered time-enhancement curves from dynamic cone beam CT imaging agreed well with that of an IV-digital subtraction angiography (DSA) study. The dynamic vascular structures reconstructed using both projection-based subtraction and reconstruction-based subtraction were almost identical as the differences between them were comparable to the background noise level. At the enhancement peak, all the major carotid and cerebral arteries and the Circle of Willis could be clearly observed. CONCLUSIONS: The proposed dynamic cone beam CT approach can accurately recover the actual contrast flow, and dynamic anatomic imaging can be obtained with high isotropic 3D resolution. This approach is promising for diagnosis and treatment planning of vascular diseases and strokes.