The mesenchymal cancer phenotype is known to be clinically related to treatment resistance and a poor prognosis. We identified gene signature-based molecular subtypes of gastric cancer (GC, n = 547) based on transcriptome data and validated their prognostic and predictive utility in multiple external cohorts. We subsequently examined their associations with tumor microenvironment (TME) features by employing cellular deconvolution methods and sequencing isolated GC populations. We further performed spatial transcriptomics analysis and immunohistochemistry, demonstrating the presence of GC cells in a partial epithelial-mesenchymal transition state. We performed network and pharmacogenomic database analyses to identify TGF-β signaling as a driver pathway and, thus, a therapeutic target. We further validated its expression in tumor cells in preclinical models and a single-cell dataset. Finally, we demonstrated that inhibition of TGF-β signaling negated mesenchymal/stem-like behavior and therapy resistance in GC cell lines and mouse xenograft models. In summary, we show that the mesenchymal GC phenotype could be driven by epithelial cancer cell-intrinsic TGF-β signaling and propose therapeutic strategies based on targeting the tumor-intrinsic mesenchymal reprogramming of medically intractable GC.

This study used magnetic resonance (MR) thermometry to investigate the temperature increases and thermal transfer that occur during plasmonic photothermal therapy (PTT) with gold nanorods (GNRs). An artificial tumor phantom made of agarose gel containing GNRs was heated by irradiation with an 808 nm laser. The MR thermometry visualized the conditions: a well-localized temperature distribution with suppressed thermal diffusion that depended on laser power and irradiation time. A tumor phantom model was implanted in mice, and MR thermometry evaluated the temperature change in the presence and absence of GNRs and the thermal transfer into the surrounding tissues. That experiment showed that MR thermometry can be a useful tool for monitoring PTT. These results suggest that MR temperature measurement could help to establish ideal laser irradiation conditions in GNR-mediated PTT, and that it has great potential for visualizing local photothermal induction and evaluating therapeutic effects.

Purpose The positron emission tomography (PET)-magnetic resonance (MR) system is a newly emerging technique that yields hybrid images with high-resolution anatomical and metabolic information. With PET-MR imaging, a definitive diagnosis of breast abnormalities will be possible with high spatial accuracy and images will be acquired for the optimal fusion of anatomic locations. Therefore, we propose a PET-compatible two-channel breast MR coil with minimal disturbance to image acquisition which can be used for simultaneous PET-MR imaging in patients with breast cancer. Materials and Methods For coil design and construction, the conductor loops of the Helmholtz coil were tuned, matched, and subdivided with nonmagnetic components. Element values were optimized with an electromagnetic field simulation. Images were acquired on a GE 600 PET-computed tomography (CT) and GE 3.0 T MR system. For this study, we used the T1-weighted image (volunteer; repetition time (TR), 694 ms; echo time (TE), 9.6 ms) and T2-weighted image (phantom; TR, 8742 ms; TE, 104 ms) with the fast spin-echo sequence. Results The results of measuring image factors with the proposed radiofrequency (RF) coil and standard conventional RF coil were as follows: signal-to-noise ratio (breast; 207.7 vs. 175.2), percent image uniformity (phantom; 89.22%-91.27% vs. 94.63%-94.77%), and Hounsfield units (phantom; -4.51 vs. 2.38). Conclusions Our study focused on the feasibility of proposed two-channel Helmholtz loops (by minimizing metallic components and soldering) for PET-MR imaging and found the comparable image quality to the standard conventional coil. We believe our work will help significantly to improve image quality with the development of a less metallic breast MR coil.

Advancements in photodynamic diagnosis (PDD) and photodynamic therapy (PDT) as a standard care in cancer therapy have been limited. This study is aimed to investigate the clinical availability of 5-aminolevulinic acid (5-ALA)-based PDD and PDT in glioblastoma (GBM) patient-derived tumorspheres (TSs) and mouse orthotopic xenograft model. PDT was performed using a 635 nm light-emitting diode (LED). Transcriptome profiles were obtained from microarray data. For knockdown of C5α, siRNA was transfected into tumor mesenchymal stem-like cells (tMSLCs). The invasiveness of TSs was quantified using collagen-based 3D invasion assays. Treatment with 1 mM 5 ALA induced distinct protoporphyrin IX (PpIX) fluorescence in GBM TSs, but not in non-tumor cells or tissues, including tMSLCs. These observations were negatively correlated with the expression levels of FECH, which catalyzes the conversion of accumulated PpIX to heme. Furthermore, the 5-ALA-treated GBM TSs were sensitive to PDT, thereby significantly decreasing cell viability and invasiveness. Notably, the effects of PDT were abolished by culturing TSs with tMSLC-conditioned media. Transcriptome analysis revealed diverse tMSLC-secreted chemokines, including C5α, and their correlations with the expression of stemness- or mesenchymal transition-associated genes. By adding or inhibiting C5α, we confirmed that acquired resistance to PDT was induced via tMSLC-secreted C5α. Our results show substantial therapeutic effects of 5-ALA-based PDT on GBM TSs, suggesting C5α as a key molecule responsible for PDT resistance. These findings could trigger PDT as a standard clinical modality for the treatment of GBM.

[This corrects the article on p. 57 in vol. 64.].

In this study, we investigated the changes in the molecular structure of polyaniline (PANI) nanoparticles illuminated by a proton beam using terahertz (THz) thermal spectroscopy based on the terahertz time-domain spectroscopy technique. PANI nanoparticles in water were exposed to a proton beam of 35 MeV energy with a particle fluence of 10(13) particles/cm(2). The photothermal properties of this solution of PANI nanoparticles were characterized using THz thermal spectroscopy. We measured the changes in the amplitudes of the reflected THz pulses to identify the variations in temperature induced by the photothermal effects of the PANI nanoparticle solution. The amplitude of a reflected THz pulse of the PANI solution not exposed to the proton beam increased when illuminated by an infrared light source, whereas that of THz signals of the PANI solution exposed to the proton beam hardly exhibited any changes. This implies that the molecular structure of PANI nanoparticles can be varied by a proton beam with a particle fluence above 10(13) particles/cm(2).

Magnetic resonance imaging (MRI) is an essential modality for the diagnosis of musculoskeletal system defects because of its higher soft-tissue contrast and spatial resolution. With the recent development of MRI-related technology, faster imaging and various image plane reconstructions are possible, enabling better assessment of three-dimensional musculoskeletal anatomy and lesions. Furthermore, the image quality, diagnostic accuracy, and acquisition time depend on the MRI protocol used. Moreover, the protocol affects the efficiency of the MRI scanner. Therefore, it is important for a radiologist to optimize the MRI protocol. In this review, we will provide guidance on patient positioning; selection of the radiofrequency coil, pulse sequences, and imaging planes; and control of MRI parameters to help optimize the MRI protocol for the six major joints of the musculoskeletal system.

A gold nanoparticle-based localized surface plasmon resonance substrate has been developed as nano-sensors for various bio-applications. However, reproducible and robust sensing substrates anchored gold nanoparticles has not yet been explored. In this study, dopamine-coated gold nanorods (DGNRs) were prepared and immobilized onto the micro-grooving PDMS substrates (mgPDMS). Subsequently, HER2-specific aptamers were conjugated with DGNR/mgPDMS for ECD-HER2 detection. By screening of the optimal concentration of DGNR and aptamers, the effective HER2-specific aptasensor was built up. In particular, the real-time binding assay for the evaluation of limit-of-detection (<5 ng ml(-1)) was conducted. Furthermore, the binding kinetics for ECD-HER2 was investigated under the biological fluid using a rat serum. Our HER2-specific aptasensor demonstrated the effective sensitivity and selectivity for ECD-HER2.

Rationale and Objectives: To compare the diagnostic ability of modified Dixon (mDixon) turbo spin echo (TSE)T1-weighted (T1W) shoulder magnetic resonance arthrography (MRA) with that of conventional shoulder MRA, and evaluate the feasibility of mDixon TSE in-phase (IP) images in measuring the fat fraction and size of rotator cuff muscles. Materials and Methods: This retrospective study included 57 patients who underwent 3T shoulder MRA examinations with conventional and mDixon TSE T1W images (mean age: 56.7 years; range: 20-78 years). Two musculoskeletal radiologists independently evaluated the rotator cuff tendons with fat saturated T1W images and mDixon TSE T1W water images. Occupation ratios measured on T1W and mDixon TSE T1W IP images were compared. The fat fraction of the supraspinatus from the mDixon TSE T1W images was calculated and correlated with fatty infiltration of the supraspinatus on T1W images. Results: For tendon pathology, the kappa value for inter-sequence and inter-reader agreement was 0.957 (95% confidence interval [CI]: 0.923-0.990) and 0.839 (95% CI: 0.778-0.899), respectively. For retear, the kappa value for inter-sequence and inter-reader agreement was 0.913 (95% CI: 0.796-1.000) and 0.779 (95% CI: 0.594-0.963), respectively. The intraclass correlation coefficient for both occupation ratios was 0.986 (95% CI: 0.973-0.993). Comparison of mDixon TSE T1W fat fraction with Goutallier grade showed a strong positive linear correlation (r = 0.929). Conclusions: The mDixon TSE T1W sequence is a good alternative to conventional sequences in shoulder MRA for evaluating rotator cuff pathology. Furthermore, this sequence provides information on the size and fat infiltration of rotator cuff muscles.

Background: Developing personalized strategies for cancer has shown good efficacies. Methods: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization. Results: Seventeen (23%) cases were TIL+ (>= 1 + expression) and associated with longer 5-year overall survival than those with TIL- tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1(+) tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1(+) tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045). Conclusions: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.

Objectives: To assess the clinical utility of a prototype sequence for metal artifact reduction, the multiacquisition variable-resonance image combination selective (MAVRIC-SL) at 3 T. This sequence allows a surgical prosthesis-dependent reduction in the number of spectral bins. We compared the prototype MAVRIC SL to the conventional two-dimensional fast spin-echo (FSE) sequences and MAVRIC SL images acquired with all spectral bins to those acquired with the optimized number of spectral bins. Methods: MAVRIC SL images were acquired in 25 image sets from August 2017 to April 2018. For each subject, the optimized number of spectral bins was determined using a short spectral calibration scan. The image sets obtained with magnetic resonance imaging that were used for the analysis consisted of MAVRIC-SL proton density (PD)-weighted or short inversion time inversion recovery (STIR) images acquired with all 24 spectral bins, the corresponding images with the optimized number of spectral bins, and the conventional two-dimensional FSE or STIR PD-weighted images. A musculoskeletal radiologist reviewed and scored the images using a five-point scale for artifact reduction around the prosthesis and visualization of the prosthesis and peri-prosthetic tissues. Quantitative evaluation of the peri-prosthetic tissues was also performed. The Wilcoxon rank-sum test was used to test for significance. Results: The MAVRIC SL images enabled a significantly improved reduction in metallic artifacts compared to the conventional two-dimensional FSE sequences. The optimized number of spectral bins ranged from 6 to 20, depending on the prosthesis susceptibility difference, size, and orientation to the B-0 field. The scan times significantly decreased with a reduced number of spectral bins (354.0 +/- 139.1 versus 283.0 +/- 89.6 s; 20% reduced scan time; p < .05). Compared to the MAVRIC SL images acquired with all 24 bins, the artifact reduction and visualization of the prosthesis and peri-prosthetic tissues on the MAVRIC SL images acquired with calibrated bins were not significantly different. Conclusions: Compared to the MAVRIC SL images acquired with all 24 spectral bins, those acquired with an optimized number of spectral bins can reduce metallic artifacts with no significant image quality degradation while providing reduced scan time.

Objectives: To investigate the feasibility of three-dimensional fast spin echo (3D-FSE) imaging with compressed sensing (CS) and parallel imaging (PI) compared to 3D-FSE imaging with only PI in evaluating ankle joint pathologies. Materials and methods: Twenty consecutive patients underwent ankle magnetic resonance imaging (MRI), including acquisition of image sets of 2D-FSE sequences, and 3D-FSE sequences without and with CS, between June 2016 and November 2017. Three MR image sets were independently rated by two radiologists for the presence/absence of ankle pathology. Quantitative image similarity and subjective image quality were evaluated using 3D-FSE images without CS and those with CS-PI. Inter-sequence agreement between 3D-FSE sequences without CS and with CS-PI in both readers was evaluated. Results: Interobserver agreements were nearly perfect for sprain of the anterior talofibular ligament (ATFL, kappa=0.77), osteochondral lesion of the talus (OLT, kappa=0.76-0.88), osteochondral lesion of the distal tibia (OLTi, kappa=0.74) and os subfibulare (OSF, kappa=0.62-0.64). The structural similarity index (mean, 0.996; range, 0.990-0.997) between the 3D-FSE sequences without CS and with CS-PI was acceptable. There was no significant difference in subjective image quality between the two imaging sequences (ATFL, p = 0.317; bone marrow, p = 0.083; cartilage, p = 1.000, tendon, p = 1.000). Intersequence agreement between the 3D-FSE sequences with and without CS was nearly perfect (ATFL and OLTi, kappa= 1.00; OLT, kappa= 0.87-0.96; OSF, kappa= 0.62-0.64) in both readers. Conclusions: Isotropic 3D-FSE ankle MRI with CS provides acceptable diagnostic performance with reduced scan time. Compressed sensing-related artifacts could be minimized with CS reconstruction enhancement, allowing for better image quality for evaluating ankle joint pathologies.

Herein, we report a de novo synthesis approach to produce bandgap-controlled polyaniline (PAni) nanostructure via Mn-mediated oxidative polymerization at the catalytic nanoreactor. To achieve systemic nanoconfined polymerization, manganese oxide (MnOx) nanoparticles coated with silica were used as the sacrificial nanotemplate. Interestingly, the catalytic nanoreactor simultaneously allowed the nanoconfined oxidative polymerization and controlling of the bandgap. MnOx could be reduced by the addition of aniline monomers and consecutive redox reaction at the nanoreactor. Furthermore, core cavity was generated, and ionized Mn could control the bandgap by coordination at the nanostructures.

We investigated the feasibility of using terahertz (THz) reflection imaging to detect keratinizing squamous cell carcinoma (SCC) of the tongue. Four fresh keratinizing SCC tissues were studied, which had been surgically resected. All of the keratinizing SCCs were well distinguished from normal healthy tissues. We showed that the tumor regions exhibited low THz reflection despite having higher water content than normal regions. The refractive indices and absorption coefficients were low in the tumor tissues despite the relatively high water content. Our results showed that there were dominant factors such as keratin pearls, other than the water content affecting the THz reflection signal.

The objectives of this study were to compare the ultrashort T2* relaxation time with the T2* relaxation time using the 3 dimensional (3D) cones sequence in 3 groups of patients with normal, degenerated, and torn knee menisci, and to demonstrate the additional effect of the ultrashort echo time (UTE) signal intensity. Following institutional review board approval, 42 knee magnetic resonance imaging (MRI) scans of 42 patients who presented with knee pain and underwent knee MRIs, with the 3D Cones of UTE sequence (minimum TEs: 32 mu s) and a 3T MRI scanner (Discovery 750, GE Healthcare, Waukesha, WI), were analyzed. The enrolled patients were classified into 3 subgroups: normal meniscus on conventional MRI, with no positive meniscus-related physical examination in medical records; meniscal degeneration with signal changes on conventional MRI; and meniscal tear. For the quantitative assessment, the mean values inside user-drawn regions of interest (ROIs) of the medial menisci were drawn on UTE T2* map and T2* map. For statistical analyses, 1-way analysis of variance (ANOVA) with post-hoc analysis using the Tukey HSD test was conducted to compare groups, and effect size was used to compare the discrimination power. The ultrashort T2* relaxation times were higher in patients with meniscal tear than in those with normal and degeneration groups (P<.05, respectively) whereas T2* relaxation times were not statistically significantly different. The ultrashort T2* relaxation times showed higher effect sizes than the T2* times between tear and normal/degeneration. The ultrashort T2* relaxation times showed better delineation of meniscal degeneration or tears than T2* relaxation times. The ultrashort T2* relaxation times could be more sensitive at differentiating between normal and pathologic meniscal conditions in patients.

Background Synthetic magnetic resonance imaging (MRI) allows reformatting of various synthetic images by adjustment of scanning parameters such as repetition time (TR) and echo time (TE). Optimized MR images can be reformatted from T1, T2, and proton density (PD) values to achieve maximum tissue contrast between joint fluid and adjacent soft tissue. Purpose To demonstrate the method for optimization of TR and TE by synthetic MRI and to validate the optimized images by comparison with conventional shoulder MR arthrography (MRA) images. Material and Methods Thirty-seven shoulder MRA images acquired by synthetic MRI were retrospectively evaluated for PD, T1, and T2 values at the joint fluid and glenoid labrum. Differences in signal intensity between the fluid and labrum were observed between TR of 500–6000 ms and TE of 80–300 ms in T2-weighted (T2W) images. Conventional T2W and synthetic images were analyzed for diagnostic agreement of supraspinatus tendon abnormalities (kappa statistics) and image quality scores (one-way analysis of variance with post-hoc analysis). Results Optimized mean values of TR and TE were 2724.7 ± 1634.7 and 80.1 ± 0.4, respectively. Diagnostic agreement for supraspinatus tendon abnormalities between conventional and synthetic MR images was excellent (κ = 0.882). The mean image quality score of the joint space in optimized synthetic images was significantly higher compared with those in conventional and synthetic images (2.861 ± 0.351 vs. 2.556 ± 0.607 vs. 2.750 ± 0.439; P < 0.05). Conclusion Synthetic MRI with optimized TR and TE for shoulder MRA enables optimization of soft-tissue contrast.

Background: This study aimed to compare computed tomography (CT) features, including tumor size and textural and histogram measurements, of giant-cell tumors of bone (GCTBs) before and after denosumab treatment and determine their applicability in monitoring GCTB response to denosumab treatment. Methods: This retrospective study included eight patients (male, 3; female, 5; mean age, 33.4 years) diagnosed with GCTB, who had received treatment by denosumab and had undergone pre-and post-treatment non-contrast CT between January 2010 and December 2016. This study was approved by the institutional review board. Pre- and post-treatment size, histogram, and textural parameters of GCTBs were compared by the Wilcoxon signed-rank test. Pathological findings of five patients who underwent surgery after denosumab treatment were evaluated for assessment of treatment response. Results: Relative to the baseline values, the tumor size had decreased, while the mean attenuation, standard deviation, entropy (all, P = 0.017), and skewness (P = 0.036) of the GCTBs had significantly increased post-treatment. Although the difference was statistically insignificant, the tumors also exhibited increased kurtosis, contrast, and inverse difference moment (P = 0.123, 0.327, and 0.575, respectively) post-treatment. Histologic findings revealed new bone formation and complete depletion or decrease in the number of osteoclast-like giant cells. Conclusion: The histogram and textural parameters of GCTBs changed significantly after denosumab treatment. Knowledge of the tendency towards increased mean attenuation and heterogeneity but increased local homogeneity in post-treatment CT histogram and textural features of GCTBs might aid in treatment planning and tumor response evaluation during denosumab treatment. (C) 2018 Published by Elsevier B.V. on behalf of The Japanese Orthopaedic Association.

To investigate the agreement between double-inversion recovery (DIR) with synthetic magnetic resonance imaging (MRI) and T1-weighted contrast-enhanced (CE)-MRI for the assessment of knee synovitis.

The purpose of this study was to assess the urgent based lung allocation system in Korea using the lung allocation score (LAS) system.

Purpose: To compare image quality between compressed sensing (CS)-3D-fast spin-echo (FSE) and conventional 3D-FSE sequences for knee magnetic resonance imaging (MRI).& para;& para;Methods: Knee MRI of 43 patients (male:female, 14:29; mean age, 53 years) were acquired using conventional and CS-3D-FSE with an acceleration factor of 1.5. Overall image quality was assessed by correlation coefficient, root-mean-square error (RMSE), and structural similarity (SSIM) index. Regional image quality was evaluated using signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs). Subjective image quality was evaluated using a four-point scale. Diagnostic agreement for meniscal lesions between the two sequences was evaluated.& para;& para;Results: The scan time was reduced from 7:14-8:08 to 4:53-5:08 with CS. A strong positive correlation was observed between data of the two sequences (mean r = 0.880). The RMSE (mean, 126.861) and SSIM index (mean, 0.987) were acceptable. The SNRs and CNRs were not significantly different between the two sequences (P > 0.05, each). There were no significant differences in the evaluation of the menisci and cruciate ligaments, while the CS images demonstrated inferior quality of cartilage-subchondral bone delineation. Diagnostic agreement for meniscal lesions between the two sequences was very good (kappa = 0.943-1).& para;& para;Conclusion: Compressed sensing-3D-FSE knee MRI produces images of acceptable quality while reducing scan time.