ZNF263 cooperates with ZNF31 to promote the drug resistance and EMT of pancreatic cancer through transactivating RNF126.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is attribute to the aggressive local invasion, distant metastasis and drug resistance of PDAC patients, which was strongly accelerated by epithelial-mesenchymal transition (EMT). In current study, we systematically investigate the role of ZNF263/RNF126 axis in the initiation of EMT in PDAC in vitro and vivo. ZNF263 is firstly identified as a novel transactivation factor of RNF126. Both ZNF263 and RNF126 were overexpressed in PDAC tissues, which were associated with multiple advanced clinical stages and poor prognosis of PDAC patients. ZNF263 overexpression promoted cell proliferation, drug resistance and EMT in vitro via activating RNF126 following by the upregulation of Cyclin D1, N-cad, and MMP9, and the downregulation of E-cad, p21, and p27. ZNF263 silencing contributed to the opposite phenotype. Mechanistically, ZNF263 transactivated RNF126 via binding to its promoter. Further investigations revealed that ZNF263 interacted with ZNF31 to coregulate the transcription of RNF126, which in turn promoted ubiquitination-mediated degradation of PTEN. The downregulation of PTEN activated AKT/Cyclin D1 and AKT/GSK-3ß/ß-catenin signaling, thereby promoting the malignant phenotype of PDAC. Finally, the coordination of ZNF263 and RNF126 promotes subcutaneous tumor size and distant liver metastasis in vivo. ZNF263, as an oncogene, promotes proliferation, drug resistance and EMT of PDAC through transactivating RNF126.

Fast Interfacial Defluorination Kinetics Enables Stable Cycling of Low-Temperature Lithium Metal Batteries.

The development of low-temperature lithium metal batteries (LMBs) encounters significant challenges because of severe dendritic lithium growth during the charging/discharging processes. To date, the precise origin of lithium dendrite formation still remains elusive due to the intricate interplay between the highly reactive lithium metal anode and organic electrolytes. Herein, we unveil the critical role of interfacial defluorination kinetics of localized high-concentration electrolytes (LHCEs) in regulating lithium dendrite formation, thereby determining the performance of low-temperature LMBs. We investigate the impact of solvation structures of LHCEs on low-temperature LMBs by employing tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF) as comparative solvents. The combination of comprehensive characterizations and theoretical simulations reveals that the THF-based LHCE featured with a strong solvation strength exhibits fast interfacial defluorination reaction kinetics, thus leading to the formation of an amorphous and inorganic-rich solid-electrolyte interphase (SEI) that can effectively suppress the growth of lithium dendrites. As a result, the highly reversible Li metal anode achieves an exceptional Coulombic efficiency (CE) of up to ∼99.63% at a low temperature of -30 °C, thereby enabling stable cycling of low-temperature LMB full cells. These findings underscore the crucial role of electrolyte interfacial reaction kinetics in shaping SEI formation and provide valuable insights into the fundamental understanding of electrolyte chemistry in LMBs.

Dynamics of T follicular helper cells in patients with rheumatic diseases and subsequent antibody responses in a three-dose immunization regimen of CoronaVac.

Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.

Recent Progress in Rechargeable Sodium Metal Batteries: A Review.

Sodium metal batteries (SMBs) have been widely studied owing to their relatively high energy density and abundant resources. However, they still need systematic improvement to fulfill the harsh operating conditions for their commercialization. In this review, we summarize the recent progress in SMBs in terms of sodium anode modification, electrolyte exploration, and cathode design. Firstly, we give an overview of the current challenges facing Na metal anodes and the corresponding solutions. Then, the traditional liquid electrolytes and the prospective solid electrolytes for SMBs are summarized. In addition, insertion- and conversion-type cathode materials are introduced. Finally, an outlook for the future of practical SMBs is provided.

IGFL2-AS1 facilitates tongue squamous cell carcinoma progression via Wnt/ß-catenin signaling pathway.

OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is the most common malignancy in oral cancer. Long noncoding RNAs (lncRNAs) are important regulators in cancer biology. In our present study, we investigated a novel lncRNA IGF-like family member 2 antisense RNA 1 (IGFL2-AS1) in TSCC. METHODS: RT-qPCR analyzed IGFL2-AS1 expression in TSCC cells. Functional assays assessed the impact of IGFL2-AS1 on TSCC cell proliferation, migration, and invasion. Western blot analyzed the protein levels of EMT-related markers. Mechanism assays analyzed the regulatory mechanism of IGFL2-AS1 in TSCC cells. In-vivo experiments were conducted to prove the role of IGFL2-AS1 in TSCC progression. RESULTS: IGFL2-AS1 was significantly up-regulated in TSCC cells and tissues, and IGFL2-AS1 knockdown inhibited cell proliferation, migration, invasion and EMT in TSCC. Moreover, IGFL2-AS1 functioned as a competing endogenous RNA (ceRNA) to sponge miR-1224-5p and thereby modulated SATB homeobox 1 (SATB1) expression. Additionally, SATB1 activated the Wnt/ß-catenin signaling pathway in TSCC cells and IGFL2-AS1 regulated the Wnt/ß-catenin signaling pathway and TSCC progression via elevating SATB1 expression. CONCLUSIONS: The data revealed that IGFL2-AS1 played a cancer promoting role in TSCC and may aid in exploring a brand new biomarker that might contribute to TSCC treatment.

High-entropy Electrolyte Enables High Reversibility and Long Lifespan for Magnesium Metal Anodes.

The stable cycling of Mg-metal anodes is limited by several problems, including sluggish electrochemical kinetics and passivation at the Mg surface. In this study, we present a high-entropy electrolyte composed of lithium triflate (LiOTf) and trimethyl phosphate (TMP) co-added to magnesium bis(trifluoromethane sulfonyl)imide (Mg(TFSI)2 /1,2-dimethoxyethane (DME) to significantly improve the electrochemical performance of Mg-metal anodes. The as-formed high-entropy Mg2+ -2DME-OTf- -Li+ -DME-TMP solvation structure effectively reduced the Mg2+ -DME interaction in comparison with that observed in traditional Mg(TFSI)2 /DME electrolytes, thereby preventing the formation of insulating components on the Mg-metal anode and promoting its electrochemical kinetics and cycling stability. Comprehensive characterization revealed that the high-entropy solvation structure brought OTf- and TMP to the surface of the Mg-metal anode and promoted the formation of a Mg3 (PO4 )2 -rich interfacial layer, which is beneficial for enhancing Mg2+ conductivity. Consequently, the Mg-metal anode achieved excellent reversibility with a high Coulombic efficiency of 98 % and low voltage hysteresis. This study provides new insights into the design of electrolytes for Mg-metal batteries.

Unraveling the Solvent Effect on Solid-Electrolyte Interphase Formation for Sodium Metal Batteries.

Ether-based electrolytes are considered as an ideal electrolyte system for sodium metal batteries (SMBs) due to their superior compatibility with the sodium metal anode (SMA). However, the selection principle of ether solvents and the impact on solid electrolyte interphase formation are still unclear. Herein, we systematically compare the chain ether-based electrolyte and understand the relationship between the solvation structure and the interphasial properties. The linear ether solvent molecules with different terminal group lengths demonstrate remarkably distinct solvation effects, thus leading to different electrochemical performance as well as deposition morphologies for SMBs. Computational calculations and comprehensive characterizations indicate that the terminal group length significantly regulates the electrolyte solvation structure and consequently influences the interfacial reaction mechanism of electrolytes on SMA. Cryogenic electron microscopy clearly reveals the difference in solid electrolyte interphase in various ether-based electrolytes. As a result, the 1,2-diethoxyethane-based electrolyte enables a high Coulombic efficiency of 99.9 %, which also realizes the stable cycling of Na||Na3 V2 (PO4 )3 full cell with a mass loading of ≈9 mg cm-2 over 500 cycles.

KLK11 acts as a tumor-inhibitor in laryngeal squamous cell carcinoma through the inactivation of Akt/Wnt/ß-catenin signaling.

Kallikrein-associated peptidase 11 (KLK11) has emerged as a key tumor-associated protein that is implicated in a wide spectrum of tumor types. However, the detailed involvement of KLK11 in laryngeal squamous cell carcinoma (LSCC) has not been well studied. The aims of our work were to evaluate whether KLK11 plays a role in LSCC. We found that both the mRNA and protein expression of KLK11 were significantly lower in LSCC tissues than in normal tissues. Low expression of KLK11 was also observed in LSCC cell lines, and the up-regulation of KLK11 caused a significant inhibitory effect on the proliferation, colony formation and invasion of LSCC cells. On the contrary, the knockdown of KLK11 markedly accelerated the proliferative and invasive abilities of LSCC cells. Molecular mechanism research revealed that KLK11 overexpression decreased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and down-regulated the expression of active ß-catenin, leading to the inactivation of Wnt/ß-catenin signaling in LSCC cells. Furthermore, GSK-3ß inhibition markedly abrogated the KLK11-mediated suppressive effect on Wnt/ß-catenin signaling. Notably, the reactivation of Wnt/ß-catenin partially reversed KLK11-mediated tumor-inhibition effect in LSCC. In addition, the xenograft tumor assay demonstrated that the up-regulation of KLK11 retarded tumor formation and the growth of LSCC cells in vivo. Taken together, the findings of our work demonstrate that KLK11 exerts a tumor-inhibition role in LSCC by down-regulating Wnt/ß-catenin signaling. Our work highlights a pivotal role of KLK11 in LSCC progression and suggests it as an attractive anticancer target for LSCC treatment.

T2*-weighted MRI as a non-contrast-enhanced method for assessment of focal laser ablation zone extent in prostate cancer thermotherapy.

OBJECTIVES: To evaluate utility of T2*-weighted (T2*W) MRI as a tool for intra-operative identification of ablation zone extent during focal laser ablation (FLA) of prostate cancer (PCa), as compared to the current standard of contrast-enhanced T1-weighted (T1W) MRI. METHODS: Fourteen patients with biopsy-confirmed low- to intermediate-risk localized PCa received MRI-guided (1.5 T) FLA thermotherapy. Following FLA, axial multiple-TE T2*W images, diffusion-weighted images (DWI), and T2-weighted (T2W) images were acquired. Pre- and post-contrast T1W images were also acquired to assess ablation zone (n = 14) extent, as reference standard. Apparent diffusion coefficient (ADC) maps and subtracted contrast-enhanced T1W (sceT1W) images were calculated. Ablation zone regions of interest (ROIs) were outlined manually on all ablated slices. The contrast-to-noise ratio (CBR) of the ablation site ROI relative to the untreated contralateral prostate tissue was calculated on T2*W images and ADC maps and compared to that in sceT1W images. RESULTS: CBRs in ablation ROIs on T2*W images (TE = 32, 63 ms) did not differ (p = 0.33, 0.25) from those in sceT1W images. Bland-Altman plots of ROI size and CBR in ablation sites showed good agreement between T2*W (TE = 32, 63 ms) and sceT1W images, with ROI sizes on T2*W (TE = 63 ms) strongly correlated (r = 0.64, p = 0.013) and within 15% of those in sceT1W images. CONCLUSIONS: In detected ablation zone ROI size and CBR, non-contrast-enhanced T2*W MRI is comparable to contrast-enhanced T1W MRI, presenting as a potential method for intra-procedural monitoring of FLA for PCa. KEY POINTS: • T2*-weighted MR images with long TE visualize post-procedure focal laser ablation zone comparably to the contrast-enhanced T1-weighted MRI. • T2*-weighted MRI could be used as a plausible method for repeated intra-operative monitoring of thermal ablation zone in prostate cancer, avoiding potential toxicity due to heating of contrast agent.

Enabling High-Voltage Lithium Metal Batteries by Manipulating Solvation Structure in Ester Electrolyte.

Lithium metal is an ideal electrode material for future rechargeable lithium metal batteries. However, the widespread deployment of metallic lithium anode is significantly hindered by its dendritic growth and low Coulombic efficiency, especially in ester solvents. Herein, by rationally manipulating the electrolyte solvation structure with a high donor number solvent, enhancement of the solubility of lithium nitrate in an ester-based electrolyte is successfully demonstrated, which enables high-voltage lithium metal batteries. Remarkably, the electrolyte with a high concentration of LiNO3 additive presents an excellent Coulombic efficiency up to 98.8 % during stable galvanostatic lithium plating/stripping cycles. A full-cell lithium metal battery with a lithium nickel manganese cobalt oxide cathode exhibits a stable cycling performance showing limited capacity decay. This approach provides an effective electrolyte manipulation strategy to develop high-voltage lithium metal batteries.

Genetic alteration patterns and clinical outcomes of elderly and secondary acute myeloid leukemia.

To illustrate the clinical and genetic features of elderly and secondary acute myeloid leukemia (AML) patients, we compared 145 elderly AML (e-AML) and 55 secondary AML (s-AML) patients with 451 young de novo AML patients. Both e-AML and s-AML patients showed lower white blood cell (WBC) and bone marrow (BM) blasts at diagnosis. NPM1, DNMT3A, and IDH2 mutations were more common while biallelic CEBPA and IDH1 mutations were less seen in e-AML patients. s-AML patients carried a higher frequency of KMT2A-AF9. In treatment response and survival, e/s-AML conferred a lower complete remission (CR) rate and shorter duration of event-free survival (EFS) and overall survival (OS) compared with young patients. In multivariate analysis, s-AML was an independent risk factor for OS but not EFS in the whole cohort. Importantly, intensive therapy tended to improve the survival of e/s-AML patients without increasing the risk of early death, and hematopoietic stem cell transplantation (HSCT) could rescue the prognosis of s-AML, which should be recommended for the treatment of fit patients.

Evaluation of Focal Laser Ablation of Prostate Cancer Using High Spectral and Spatial Resolution Imaging: A Pilot Study.

BACKGROUND: Focal laser ablation (FLA) is a minimally invasive thermal ablation, guided by MRI through an optical fiber, to induce coagulative necrosis in cancer. PURPOSE: To evaluate the feasibility of high spectral and spatial resolution imaging using multiecho gradient echo (MEGE) MRI for identification of ablation zones, after FLA of prostate cancers. STUDY TYPE: Prospective. POPULATION: Fourteen patients with biopsy-confirmed localized prostate cancers. FIELD STRENGTH/SEQUENCE: FLA was performed under monitored conscious sedation with a 1.5T MRI scanner. Axial MEGE images were acquired before and after the last FLA. Pre- and postcontrast enhanced T1 -weighted (pT1 W) images were acquired to assess the FLA zone as a reference standard. ASSESSMENT: The T 2 * maps and water resonance peak height (WPH) images were calculated from the MEGE data. Ablation area was outlined using an active contour method. The maximum ablation area and total ablation volume were calculated from T 2 * and WPH images, and compared with the sizes measured from pT1 W images. STATISTICAL TESTS: Nonparametric Kruskal-Wallis tests were performed to determine whether there was significant difference in calculated ablation areas and volumes between T 2 * , WPH, and pT1 W images. RESULTS: Average T 2 * (38.9 ± 14.1 msec) in the ablation area was significantly shorter (P = 0.03) than the preablation area T 2 * (57.8 ± 25.3 msec). The normalized WPH value over the ablation area (1.3 ± 0.6) was significantly decreased (P = 0.02) more than the preablation area (2.0 ± 0.9). The maximum ablation areas measured by T 2 * (295.7 ± 96.4 mm2 ), WPH (312.2 ± 63.0 mm2 ), and pT1 W (320.3 ± 82.9 mm2 ) images were all similar. Furthermore, there was no significant difference (P = 0.31) for measured ablation volumes 3310.5 ± 649.5, 3406.4 ± 684.9, and 3672.5 ± 832.4 mm3 between T 2 * , WPH, and pT1 W images, respectively. DATA CONCLUSION: T 2 * and WPH images provide acceptable measurements of ablation zones during FLA treatment of prostate cancers without the need for contrast agent injection. This might allow repeated assessment following each heating period so that subsequent ablations can be optimized. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;49:1374-1380.

Diagnosis of Prostate Cancer with Noninvasive Estimation of Prostate Tissue Composition by Using Hybrid Multidimensional MR Imaging: A Feasibility Study.

Purpose To evaluate whether compartmental analysis by using hybrid multidimensional magnetic resonance (MR) imaging can be used to diagnose prostate cancer and determine its aggressiveness. Materials and Methods Twenty-two patients with prostate cancer underwent preoperative 3.0-T MR imaging. Axial images were obtained with hybrid multidimensional MR imaging by using all combinations of echo times (47, 75, 100 msec) and b values of 0, 750, 1500 sec/mm2, resulting in a 3 × 3 array of data associated with each voxel. Volumes of the tissue components stroma, epithelium, and lumen were calculated by fitting the hybrid data to a three-compartment signal model, with distinct, paired apparent diffusion coefficient (ADC) and T2 values associated with each compartment. Volume fractions and conventional ADC and T2 were measured for regions of interest in sites of prostatectomy-verified malignancy (n = 28) and normal tissue (n = 71). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of various parameters in differentiating prostate cancer from benign tissue. Results Compared with normal tissue, prostate cancer showed significantly increased fractional volumes of epithelium (23.2% ± 7.1 vs 48.8% ± 9.2, respectively) and reduced fractional volumes of lumen (26.4% ± 14.1 vs 14.0% ± 5.2) and stroma (50.5% ± 15.7 vs 37.2% ± 9.1) by using hybrid multidimensional MR imaging. The fractional volumes of tissue components show a significantly higher Spearman correlation coefficient with Gleason score (epithelium: ρ = 0.652, P = .0001; stroma: ρ = -0.439, P = .020; lumen: ρ = -0.390, P = .040) compared with traditional T2 values (ρ = -0.292, P = .132) and ADCs (ρ = -0.315, P = .102). The area under the ROC curve for differentiation of cancer from normal prostate was highest for fractional volume of epithelium (0.991), followed by fractional volumes of lumen (0.800) and stroma (0.789). Conclusion Fractional volumes of prostatic lumen, stroma, and epithelium change significantly when cancer is present. These parameters can be measured noninvasively by using hybrid multidimensional MR imaging and have the potential to improve the diagnosis of prostate cancer and determine its aggressiveness. © RSNA, 2018 Online supplemental material is available for this article.

Pre-treatment lymphopenia and indication of tumor-induced systemic immunosuppression in medulloblastoma.

The presence of tumor-induced systemic immune suppression, including lymphopenia, has been recognized in adult patients with glioblastoma for several decades, and pre-treatment neutrophil-to-lymphocyte count ratio (NLCR) is associated with inferior clinical outcome in patients with glioblastoma. Whether tumor-induced systemic immune suppression is also present in children with malignant brain tumors is not known. We performed a retrospective analysis of pretreatment neutrophil and lymphocyte counts in pediatric patients with medulloblastoma (MB) compared to a control group of children with posterior fossa pilocytic astrocytoma (PA). Compared to the control group, we observed statistically significantly lower absolute lymphocyte counts (ALCs) and higher NLCRs in the medulloblastoma group. Our findings suggest the presence of tumor-induced systemic immune suppression in MB patients already present at the time of diagnosis, with potential implications for the development of immune therapies in this population.

Programmed death ligand 1 expression and tumor infiltrating lymphocytes in neurofibromatosis type 1 and 2 associated tumors.

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or its ligand (PD-L1) have been shown to be effective in treating patients with a variety of cancers. Biomarker studies have found positive associations between clinical response rates and PD-L1 expression on tumor cells, as well as the presence of tumor infiltrating lymphocytes (TILs). It is currently unknown whether tumors associated with neurofibromatosis types 1 and 2 (NF1 and NF2) express PD-L1. We performed immunohistochemistry for PD-L1 (clones SP142 and E1L3N), CD3, CD20, CD8, and CD68 in NF1-related tumors (ten dermal and six plexiform neurofibromas) and NF2-related tumors (ten meningiomas and ten schwannomas) using archival formalin-fixed paraffin-embedded tissues. Expression of PD-L1 was considered positive in cases with > 5% membranous staining of tumor cells, in accordance with previously published biomarker studies. PD-L1 expression in tumor cells (using the SP142 and E1L3N clones, respectively) was assessed as positive in plexiform neurofibromas (6/6 and 5/6) dermal neurofibromas (8/10 and 6/10), schwannomas (7/10 and 10/10), and meningiomas (4/10 and 2/10). Sparse to moderate presence of CD68, CD3, or CD8 positive TILs was found in 36 (100%) of tumor specimens. Our findings indicate that adaptive resistance to cell-mediated immunity may play a major role in the tumor immune microenvironment of NF1 and NF2-associated tumors. Expression of PD-L1 on tumor cells and the presence of TILs suggest that these tumors might be responsive to immunotherapy with immune checkpoint inhibitors, which should be explored in clinical trials for NF patients.

MRI Findings After MRI-Guided Focal Laser Ablation of Prostate Cancer.

OBJECTIVE: The purpose of this study is to describe the quantitative and qualitative findings of multiparametric prostate MRI performed after MRI-guided focal laser ablation of prostate cancer. MATERIALS AND METHODS: A total of 27 consenting patients met the study inclusion criteria, which included but were not limited to the presence of clinical category T1c-T2a prostate cancer with a Gleason score of 7 or less, having undergone prostate biopsy before and after focal laser ablation, and having undergone MRI before ablation, immediately after ablation, and 3 and 12 months after ablation. Signal changes were evaluated both qualitatively and quantitatively and were then correlated with the results of subsequent biopsy performed at 3 and 12 months after ablation. RESULTS: MRI performed immediately after ablation revealed a hypovascular defect in the ablation zone, with patchy or bandlike decreased T2 signal most commonly noted at 3 months (in 66.7% of ablated lesions) and T2 scarring observed in most lesions (66.7%) at 12 months. Patchy or bandlike decreased apparent diffusion coefficient signal and scarlike changes were most prevalent at 3 months after ablation (50.0% of lesions), and these features remained the most commonly observed findings at 12 months after ablation (27.8% of lesions). At 12 months after ablation, 10 patients were found to have recurrent tumor, with three patients found to have persistent cancer when biopsy was performed at the ablation site. All postablation biopsy cases with positive results showed suspicious T2 and apparent diffusion coefficient characteristics, which were considered to be a well-defined nodular intermediate signal on both of these sequences. Two of the patients for whom positive biopsy findings were noted had focal enhancement of the ablation zone. A significant reduction in the forward volume transfer constant after ablation was found at the ablation site on follow-up examination. CONCLUSION: Multiparametric MRI can reveal postablation changes in the prostate and can be a valuable tool for monitoring patients who have undergone MRI-guided focal laser ablation.

Phase II Evaluation of Magnetic Resonance Imaging Guided Focal Laser Ablation of Prostate Cancer.

PURPOSE: Magnetic resonance imaging guided focal laser ablation is an investigational strategy for the treatment of prostate cancer. MATERIALS AND METHODS: This phase II evaluation of focal laser ablation included men with stage T1c-T2a, prostate specific antigen less than 15 ng/ml or prostate specific antigen density less than 0.15 ng/ml3, Gleason 7 or less in 25% or less of biopsies and magnetic resonance imaging with 1 or 2 lesions concordant with biopsy detected cancer. At 3 months all patients underwent magnetic resonance imaging with biopsy of ablation zone(s). At 12 months all underwent magnetic resonance imaging and systematic biopsy. I-PSS (International Prostate Symptom Score) and SHIM (Sexual Health Inventory for Men) scores were collected before focal laser ablation, and at 1, 3 and 12 months. The primary end point was no cancer on the 3-month ablation zone biopsy. Secondary end points were safety, 12-month biopsy, and urinary and sexual function. RESULTS: In the 27 men median age was 62 years and mean prostate specific antigen was 4.4 ng/ml. Biopsy Gleason score was 6 in 23 patients (85%) and Gleason 7 in 4 (15%). Seven men (26%) had low volume Gleason 6 disease outside the intended ablation zone(s). At 3 months 26 patients (96%) had no evidence of cancer on magnetic resonance imaging guided biopsy of the ablation zone. No significant I-PSS changes were observed (each p >0.05). SHIM was lower at 1 month (p = 0.03), marginally lower at 3 months (p = 0.05) and without a significant difference at 12 months (p = 0.38). At 12-month biopsy cancer was identified in 10 patients (37%), including in the ablation zone(s) in 3 (11%) and outside the ablation zone(s) in 8 (30%) with cancer in and outside the ablation zone in 1. CONCLUSIONS: In select men with localized prostate cancer and visible magnetic resonance imaging lesions focal laser ablation has an acceptable morbidity profile and is associated with encouraging short-term oncologic outcomes. Significantly longer followup is mandatory to fully assess this novel treatment.

Evaluation of radiation-induced peripheral nerve injury in rabbits with MR neurography using diffusion tensor imaging and T2 measurements: Correlation with histological and functional changes.

PURPOSE: To investigate the potential of diffusion tensor imaging (DTI) and T2 measurements in the evaluation of radiation-induced peripheral nerve injury (RIPNI). MATERIALS AND METHODS: RIPNI was produced in a randomly selected side of sciatic nerve in each of 21 rabbits while the contralateral side served as the control. The limb function and MR parameters were evaluated over a 4-month period. Fractional anisotropy (FA), axial diffusivity (λ∥ ), radial diffusivity (λ⊥ ) and T2 values were obtained using 3T MR for quantitative analysis. Two animals were randomly killed for histological evaluation at each timepoint. RESULTS: The T2 value of irradiated nerve increased at 1 day (63.95 ± 15.60, P = 0.012) and was restored at 1 month (52.34 ± 5.38, P = 0.105). It increased progressively at 2 to 4 months (60.39 ± 10.60, 66.96 ± 6.08, 75.51 ± 7.39, all P < 0.01). λ⊥ significantly increased at 1 day (0.82 ± 0.44, P = 0.046) and slightly decreased at 1 month (0.61 ± 0.17, P < 0.001). It increased gradually from 2 to 3 months (0.84 ± 0.29, 1.13 ± 0.33, both P < 0.001) followed by a decline at 4 months (0.83 ± 0.17, P < 0.001). FA was statistically lower than the contralateral sides at 1 to 4 months (0.72 ± 0.08, 0.60 ± 0.12, 0.51 ± 0.11, 0.62 ± 0.06, all P < 0.01). Changes in FA and λ⊥ correlated well with the functional and pathological changes in irradiated nerve. CONCLUSION: DTI may be a more sensitive and accurate method to evaluate RIPNI compared with T2 measurements. FA and λ⊥ are promising quantitative indices in monitoring RIPNI. J. Magn. Reson. Imaging 2016;43:1492-1499.

Pilot Study of the Use of Hybrid Multidimensional T2-Weighted Imaging-DWI for the Diagnosis of Prostate Cancer and Evaluation of Gleason Score.

OBJECTIVE: The objective of our study was to evaluate the role of a hybrid T2-weighted imaging-DWI sequence for prostate cancer diagnosis and differentiation of aggressive prostate cancer from nonaggressive prostate cancer. MATERIALS AND METHODS: Twenty-one patients with prostate cancer who underwent preoperative 3-T MRI and prostatectomy were included in this study. Patients underwent a hybrid T2-weighted imaging-DWI examination consisting of DW images acquired with TEs of 47, 75, and 100 ms and b values of 0 and 750 s/mm(2). The apparent diffusion coefficient (ADC) and T2 were calculated for cancer and normal prostate ROIs at each TE and b value. Changes in ADC and T2 as a function of increasing the TE and b value, respectively, were analyzed. A new metric termed "PQ4" was defined as the percentage of voxels within an ROI that has increasing T2 with increasing b value and has decreasing ADC with increasing TE. RESULTS: ADC values were significantly higher in normal ROIs than in cancer ROIs at all TEs (p < 0.0001). With increasing TE, the mean ADC increased 3% in cancer ROIs and increased 12% in normal ROIs. T2 was significantly higher in normal ROIs than in cancer ROIs at both b values (p ≤ 0.0002). The mean T2 decreased with increasing b value in cancer ROIs (ΔT2 = -17 ms) and normal ROIs (ΔT2 = -52 ms). PQ4 clearly differentiated normal ROIs from prostate cancer ROIs (p = 0.0004) and showed significant correlation with Gleason score (ρ = 0.508, p < 0.0001). CONCLUSION: Hybrid MRI measures the response of ADC and T2 to changing TEs and b values, respectively. This approach shows promise for detecting prostate cancer and determining its aggressiveness noninvasively.

Short-term reproducibility of apparent diffusion coefficient estimated from diffusion-weighted MRI of the prostate.

PURPOSE: The purpose of the study is to determine short-term reproducibility of apparent diffusion coefficient (ADC) estimated from diffusion-weighted magnetic resonance (DW-MR) imaging of the prostate. METHODS: Fourteen patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Each patient underwent two, consecutive and identical DW-MR scans on a 3T system. ADC values were calculated from each scan and a deformable registration was performed to align corresponding images. The prostate and cancerous regions of interest (ROIs) were independently analyzed by two radiologists. The prostate volume was analyzed by sextant. Per-voxel absolute and relative percentage variations in ADC were compared between sextants. Per-voxel and per-ROI variations in ADC were calculated for cancerous ROIs. RESULTS: Per-voxel absolute difference in ADC in the prostate ranged from 0 to 1.60 × 10(-3) mm(2)/s (per-voxel relative difference 0% to 200%, mean 10.5%). Variation in ADC was largest in the posterior apex (0% to 200%, mean 11.6%). Difference in ADC variation between sextants was not statistically significant. Cancer ROIs' per-voxel variation in ADC ranged from 0.001 × 10(-3) to 0.841 × 10(-3) mm(2)/s (0% to 67.4%, mean 11.2%) and per-ROI variation ranged from 0 to 0.463 × 10(-3) mm(2)/s (mean 0.122 × 10(-3) mm(2)/s). CONCLUSIONS: Variation in ADC within the human prostate is reasonably small, and is on the order of 10%.