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Supplementary Figures 1-3, Tables 1-3, Methods from Definition of Ubiquitination Modulator COP1 as a Novel Therapeutic Target in Human Hepatocellular Carcinoma

An increase in hyperpolarized (HP) [1‐13C]lactate production has been suggested as a biomarker for cancer occurrence as well as for response monitoring of cancer treatment. Recently, the use of metformin has been suggested as an anticancer or adjuvant treatment. By regulating the cytosolic NAD+/NADH redox state, metformin stimulates lactate production and increases the HP [1‐13C]lactate conversion rate in the kidney, liver, and heart. In general, increased HP [1‐13C]lactate is regarded as a sign of cancer occurrence or tumor growth. Thus, the relationship between the tumor suppression effect of metformin and the change in metabolism monitored by HP [1‐13C]pyruvate MRS in cancer treatment needs to be investigated. The present study was performed using a brain metastasis animal model with MDA‐MB‐231(BR)‐Luc breast cancer cells. HP [1‐13C]pyruvate MRS, T 2‐weighted MRI, and bioluminescence imaging were performed in groups treated with metformin or adjuvant metformin and radiation therapy. Metformin treatment alone did not display a tumor suppression effect, and the HP [1‐13C]lactate conversion rate increased. In radiation therapy, the HP [1‐13C]lactate conversion rate decreased with tumor suppression, with a p‐value of 0.028. In the adjuvant metformin and radiation treatment, the tumor suppression effect increased, with a p‐value of 0.001. However, the apparent HP [1‐13C]lactate conversion rate (K pl) was observed to be offset by two opposite effects: a decrease on radiation therapy and an increase caused by metformin treatment. Although HP [1‐13C]pyruvate MRS could not evaluate the tumor suppression effect of adjuvant metformin and radiation therapy due to the offset phenomenon, metabolic changes following only metformin pre‐treatment could be monitored. Therefore, our results indicate that the interpretation of HP [1‐13C]pyruvate MRS for response monitoring of cancer treatment should be carried out with caution when metformin is used as an adjuvant cancer therapy., 1. Metformin increased HP [1‐13C] lactate/pyruvate (K pl) without tumor suppression. 2. Adjuvant metformin sensitized the radiation‐induced tumor suppression effect. However, the K pl was observed to be offset by two opposite effects: a decrease on radiation therapy and an increase caused by metformin treatment.

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. T1-weighted CE-MRI and synthetic MRI of 30 patients were compared. Synthetic DIR image reconstruction was performed with two inversion times (280–330 ms and 2800–2900 ms). Subjective image quality, visibility of synovium, detection of synovitis, and total synovitis score in the knee joint were evaluated on both MR images. The relative signal intensity (SI) and relative contrast of synovium, joint effusion, and bone marrow for two imaging were assessed. Differences in data between two imaging were assessed by using Wilcoxon’s signed-rank test and chi-square test/Fisher’s exact test. Interobserver agreement was expressed as weighted kappa value. Accuracy of synthetic DIR image was calculated by using CE-MRI as reference standard. T1-weighted CE-MRI yielded better image quality than synthetic DIR imaging (p

Purpose To test the feasibility of using the SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation) technique, which uses the partial separability of spectroscopic data, for high resolution hyperpolarized (HP) 13 C spectroscopic imaging. Methods Numerical simulations were performed to investigate the impact of transient HP signals on SPICE reconstruction. Furthermore, spectroscopic imaging exams from SPICE and conventional EPSI (echo-planar spectroscopic imaging) were simulated for comparison. For in vivo experiments, HP 13 C SPICE was performed in a mouse kidney by means of the injection of HP [1-13 C] pyruvate at 9.4T. Results The variation of lactate/pyruvate from the simulated SPICE was less than 4% under various factors that affect the transient HP signal, suggesting that the impact is negligible. We found that while HP 13 C EPSI was limited to the low signal-to-noise ratio (SNR) of lactate, these limitations were mitigated through HP 13 C SPICE, facilitating the improved SNR of lactate and the distinction of tissues. Acquisition of a high resolution HP 13 C spectroscopic image was possible for the in vivo experiments. With the fine structural information, the acquired image showed higher signal of pyruvate and lactate in the renal cortices than in the medullas, which is known to be attributed to higher activity of lactate dehydrogenase. Conclusion The feasibility of HP 13 C SPICE was investigated. Simulation studies were conducted and in vivo experiments were performed in the mouse kidney at 9.4T. Results confirmed that a high resolution HP 13 C spectroscopic image with adequate spectral resolution can be obtained. Magn Reson Med 80:703-710, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

The purpose was to evaluate the feasibility of quantitative MRI T2 mapping based on the quantitative MRI (QRAPMASTER) sequence for the quantitative assessment of knee cartilage. The T2 values from the phantom study showed excellent correlation between the two techniques (r2 = 0.998). The cartilage T2 values exhibited strong correlations (r2 = 0.867-0.982). Quantitative MRI (qMRI) T2 mapping can be used as an alternative to multi-echo T2 mapping, with relatively short scan time.

The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, p-Akt, and p-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal.

This study aims to investigate the feasibility of dynamic hyperpolarized 13 C MR spectroscopic imaging (MRSI) using the SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE) technique and an estimation of the spatially resolved conversion constant rate (kpl ). An acquisition scheme comprising a single training dataset and several imaging datasets was proposed considering hyperpolarized 13 C circumstances. The feasibility and advantage of the scheme were investigated in two parts: (a) consistency of spectral basis over time and (b) accuracy of the estimated kpl . The simulations and in vivo experiments support accurate kpl estimation with consistent spectral bases. The proposed method was implemented in an enzyme phantom and via in vivo experiments. In the enzyme phantom experiments, spatially resolved homogeneous kpl maps were observed. In the in vivo experiments, normal diet (ND) mice and high-fat diet (HFD) mice had kpl (s-1 ) values of medullar (ND: 0.0119 ± 0.0022, HFD: 0.0195 ± 0.0005) and cortical (ND: 0.0148 ±0.0023, HFD: 0.0224 ±0.0054) regions which were higher than vascular (ND: 0.0087 ±0.0013, HFD: 0.0132 ±0.0050) regions. In particular, the kpl value in the medullar region exhibited a significant difference between the two diet groups. In summary, the feasibility of using modified SPICE for dynamic hyperpolarized 13 C MRSI was demonstrated via simulations and in vivo experiments. The consistency of spectral bases over time and the accuracy of the estimated kpl values validate the proposed acquisition scheme, which comprises only a single training dataset. The proposed method improved the spatial resolution of dynamic hyperpolarized 13 C MRSI, which could be used for kpl estimation using high signal-to-noise ratio spectral bases.

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.

This study aims to investigate the feasibility of dynamic hyperpolarized

Purpose To optimize and investigate the influence of bipolar gradients for flow suppression in metabolic quantification of hyperpolarized 13C chemical shift imaging (CSI) of mouse liver at 9.4 T. Methods The trade-off between the amount of flow suppression using bipolar gradients and T2* effect from static spins was simulated. A free induction decay CSI sequence with alternations between the flow-suppressed and non–flow-suppressed acquisitions for each repetition time was developed and was applied to liver tumor–bearing mice via injection of hyperpolarized [1-13C] pyruvate. Results The in vivo results from flow suppression using the velocity-optimized bipolar gradient were comparable with the simulation results. The vascular signal was adequately suppressed and signal loss in stationary tissue was minimized. Application of the velocity-optimized bipolar gradient to tumor-bearing mice showed reduction in the vessel-derived pyruvate signal contamination, and the average lactate/pyruvate ratio increased by 0.095 (P

Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-β-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia.

Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer’s disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6 months, hyperpolarized [1-13C] pyruvate MR spectroscopy showed decreased perfusion (p

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, κ=0.77), osteochondral lesion of the talus (OLT, κ=0.76-0.88), osteochondral lesion of the distal tibia (OLTi, κ=0.74) and os subfibulare (OSF, κ=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, κ=1.00; OLT, κ=0.87-0.96; OSF, κ=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.

Obesity-related metabolic disorders can affect not only systemic health but also brain function. Recent studies have elucidated that amyloid beta deposition cannot satisfactorily explain the development of Alzheimer's disease (AD) and that dysregulation of glucose metabolism is a critical factor for the sporadic onset of non-genetic AD. Identifying the pathophysiology of AD due to changes in brain metabolism is crucial; however, it is limited in measuring changes in brain cognitive function due to metabolic changes in animal models. The touchscreen-based automated battery system, which is more accurate and less invasive than conventional behavioral test tools, is used to assess the cognition of mice with dysregulated metabolism. This system was introduced in humans to evaluate cognitive function and was recently back-translated in monkeys and rodents. We used outbred ICR mice fed on high-fat diet (HFD) and performed the paired associates learning (PAL) test to detect their visual memory and new learning ability loss as well as to assess memory impairment. The behavioral performance of the HFD mice was weaker than that of normal mice in the training but was not significantly associated with motivation. In the PAL test, the average number of trials completed and proportion of correct touches was significantly lower in HFD mice than in normal diet-fed mice. Our results reveal that HFD-induced metabolic dysregulation has detrimental effects on operant learning according to the percentage of correct responses in PAL. These findings establish that HFD-induced metabolic stress may have an effect in accelerating AD-like pathogenesis., Graphical Abstract

The purpose was to evaluate the feasibility of quantitative MRI T2 mapping based on the quantitative MRI (QRAPMASTER) sequence for the quantitative assessment of knee cartilage. The T2 values from the phantom study showed excellent correlation between the two techniques (r2 = 0.998). The cartilage T2 values exhibited strong correlations (r2 = 0.867–0.982). Quantitative MRI (qMRI) T2 mapping can be used as an alternative to multi-echo T2 mapping, with relatively short scan time.

To assess the usefulness of T2*-corrected fat fraction (FF) map from volume-interpolated breathhold examination (VIBE) magnetic resonance (MR) sequence in patients with the rotator cuff pathology.The phantom study was performed to validate the FF maps. Eighty-nine shoulder MR arthrographies were analyzed: (1) divided into three groups namely tendinopathy/normal tendons, partial-thickness tears, and full-thickness tears, and (2) occupation ratio (OR) was measured for muscular atrophy. Uncorrected and T2*-corrected FF maps were reconstructed from the VIBE images. The Pearson correlation test was used to correlate the FFs with ORs. The FF and the OR were compared between groups using the Student t test.T2*-corrected FF maps could provide a higher correlation than uncorrected FF maps. There were significantly negative correlations between the ORs and the FFs (P.01). In the normal and the partial-thickness tear group, the OR did not show a significant difference, although the FF maps showed a significant difference (P.01).This quantitative assessment of the T2*-corrected FF in the rotator cuff muscles was found to be reliable and correlated well with the ORs. The T2*-corrected FF maps could be used for more sophisticated assessments of the fat even in the partial-thickness tear.

BackgroundDual-energy computed tomography (DECT) images may be underutilized for the evaluation of skeletal metastasis. Spectral parametric segmentation of DECT can produce bone-iodine separated images, which have the potential to detect bone metastases.PurposeTo evaluate the potential of bone-iodine separation in the detection of bone metastasis with spectral parametric segmentation of DECT images which are acquired at clinical follow-up for patients with prior malignancy.Material and MethodsThe institutional review board approved the protocol of this retrospective review. Chest DECT scans using fast kV-switching between 80 and 140 kVp were included in this study. Bone-iodine separated reformatted images were produced by spectral parametric segmentation of synthesized monochromatic images. All chest CT images of 702 metastatic lesions from 54 patients were retrospectively evaluated in terms of visualization of metastatic lesions compared with99mTc-MDP (methylene diphosphonate) whole-body bone scintigraphy (WBBS) as reference standard of diagnosis.ResultsSpectral parametric segmentation images of DECT visualized metastatic lesions in 92.3% ( n = 648/702). Osteoblastic metastases were delineated as subtle enhancing lesions on DECT in comparison to WBBS.ConclusionSpectral parametric segmentation of iodine from cortical and medullary bone allowed visualization of bone metastasis. DECT might be utilized for the screening or detection of bone metastases.

Figure S1. Hyperpolarized [1-13C]lactate/[1-13C]pyruvate ratio in medial temporal lobe showed a negative correlation with time to spent in the target quadrant (n = 9, Pearson’s r = − 0.692, P

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 Conclusion Synthetic MRI with optimized TR and TE for shoulder MRA enables optimization of soft-tissue contrast.

To test the feasibility of using the SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation) technique, which uses the partial separability of spectroscopic data, for high resolution hyperpolarized (HP)Numerical simulations were performed to investigate the impact of transient HP signals on SPICE reconstruction. Furthermore, spectroscopic imaging exams from SPICE and conventional EPSI (echo-planar spectroscopic imaging) were simulated for comparison. For in vivo experiments, HPThe variation of lactate/pyruvate from the simulated SPICE was less than 4% under various factors that affect the transient HP signal, suggesting that the impact is negligible. We found that while HPThe feasibility of HP

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.

To evaluate the feasibility of 3D fast spin-echo (FSE) imaging with compressed sensing (CS) for the assessment of shoulder.Twenty-nine patients who underwent shoulder MRI including image sets of axial 3D-FSE sequence without CS and with CS, using an acceleration factor of 1.5, were included. Quantitative assessment was performed by calculating the root mean square error (RMSE) and structural similarity index (SSIM). Two musculoskeletal radiologists compared image quality of 3D-FSE sequences without CS and with CS, and scored the qualitative agreement between sequences, using a five-point scale. Diagnostic agreement for pathologic shoulder lesions between the two sequences was evaluated.The acquisition time of 3D-FSE MRI was reduced using CS (3min 23s vs. 2min 22s). Quantitative evaluations showed a significant correlation between the two sequences (r=0.872-0.993, p0.05) and SSIM was in an acceptable range (0.940-0.993; mean±standard deviation, 0.968±0.018). Qualitative image quality showed good to excellent agreement between 3D-FSE images without CS and with CS. Diagnostic agreement for pathologic shoulder lesions between the two sequences was very good (κ=0.915-1).The 3D-FSE sequence with CS is feasible in evaluating the shoulder joint with reduced scan time compared to 3D-FSE without CS.

OBJECTIVE To assess the feasibility of T2*-corrected fat-signal fraction (FF) map by using the three-echo volume interpolated breath-hold gradient echo (VIBE) Dixon sequence to differentiate between malignant marrow-replacing lesions and benign red marrow deposition of vertebrae. MATERIALS AND METHODS We assessed 32 lesions from 32 patients who underwent magnetic resonance imaging after being referred for assessment of a known or possible vertebral marrow abnormality. The lesions were divided into 21 malignant marrow-replacing lesions and 11 benign red marrow depositions. Three sequences for the parameter measurements were obtained by using a 1.5-T MR imaging scanner as follows: three-echo VIBE Dixon sequence for FF; conventional T1-weighted imaging for the lesion-disc ratio (LDR); pre- and post-gadolinium enhanced fat-suppressed T1-weighted images for the contrast-enhancement ratio (CER). A region of interest was drawn for each lesion for parameter measurements. The areas under the curve (AUC) of the parameters and their sensitivities and specificities at the most ideal cutoff values from receiver operating characteristic curve analysis were obtained. AUC, sensitivity, and specificity were respectively compared between FF and CER. RESULTS The AUCs of FF, LDR, and CER were 0.96, 0.80, and 0.72, respectively. In the comparison of diagnostic performance between the FF and CER, the FF showed a significantly larger AUC as compared to the CER (p = 0.030), although the difference of sensitivity (p = 0.157) and specificity (p = 0.157) were not significant. CONCLUSION Fat-signal fraction measurement using T2*-corrected three-echo VIBE Dixon sequence is feasible and has a more accurate diagnostic performance, than the CER, in distinguishing benign red marrow deposition from malignant bone marrow-replacing lesions.

Fluid-sensitive MR imaging in postoperative evaluation is important, however, metallic artifacts is inevitable. The purpose is to investigate the feasibility of fat-saturated slice encoding for metal artifact correction (SEMAC)-corrected T2-weighted magnetic resonance (MR) at 3T in patients with spinal prostheses.Following institutional review board approval, 27 SEMAC-encoded spinal MRs between September 2012 and October 2013 in patients with spinal metallic prostheses were analyzed. The MR images were scanned on a 3T MR system including SEMAC-corrected and uncorrected fast spin echo (FSE) T2-weighted MR images with fat-saturation. Two musculoskeletal radiologists compared the image sets and qualitatively analyzed the images using a five-point scale in terms of artifact reduction around the prosthesis, visualization of the prosthesis and pedicle, and intervertebral neural foramina. Quantitative assessments were performed by calculating the ratio of signal intensity from the fixated vertebra and that from upper level vertebra. For statistical analyses, paired t-test was used.Fat-saturated SEMAC-corrected T2-weighted MR images enabled significantly improved metallic artifact reduction (P0.05). Quantitative evaluation of the signal intensity ratio of screw-fixated vertebra and upper level vertebra showed a significantly lower ratio on fat-saturated SEMAC images (P0.05), however, the high signal intensity of signal pile-up could be not completely corrected.SEMAC correction in fat-suppressed T2-weighted MR images can overcome the signal loss of metallic artifacts and provide improved delineation of the pedicle screw and peri-prosthetic region. Signal pile-up, however, could not be corrected completely, therefore readers should be cautious in the evaluation of marrow around the prosthesis.

Background Ultrashort echo time (UTE) image to directly visualize short T2 tissues requires postprocessing for the suppression of the surrounding long T2 tissues in a clinical magnetic resonance imaging (MRI) scanner. Weighted subtraction of UTE images with an optimal weighting factor could provide high positive contrast with adequate suppression. Purpose To demonstrate in-vivo UTE MRI with weighted subtractions of dual echo UTE imaging using a 3 T clinical MRI and to determine the optimal weighting factors through the analyses of signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs). Material and Methods Forty-seven consecutive knee MR including dual echo 3D UTE sequence (TE of 70 µs and 3.82 ms) were reviewed. Seven patients with normal findings in the knee MR were included in the current study. For variably weighted subtraction images, the initial UTE image was rescaled relative to that of the second echo image with weighting factors from 0.1 to 4.0. Thirty-five pairs of the ROI measurements of the UTE image and second long echo images were repeated after 2 weeks. For quantitative assessment, SNR and CNR were measured from the ROIs on the patellar tendon, cartilage, cortical bone, meniscus, and infrapatellar fat pad. Intra-observer agreement was assessed by using both Cohen’s Kappa and Bland-Altman approach. Results The short T2 tissue could be visualized with adequate suppression on the subtraction images. Considering the CNRs and SNRs, the optimal ranges of the weighting factors could be suggested: 0.3 for the tendon, 0.4 for the cortical bone, and 1.0 for the meniscus. The 35 paired measurements showed excellent agreement with statistical significance ( P Conclusion The 3D UTE MRI provides imaging of short T2 tissues which cannot be visualized by conventional MRI. Using weighted subtractions with optimal weighting values, each tissue can be optimally depicted by overcoming the reduced T2 contrast.

One of the holy grails in biomedical imaging technology is to achieve accurate imaging of biological targets. The development of sophisticated instrumentation and the use of contrast agents have improved the accuracy of biomedical imaging. However, the issue of false imaging remains a problem. Here, we developed a dual-mode artifact filtering nanoparticle imaging agent (AFIA) that comprises a combination of paramagnetic and superparamagnetic nanomaterials. This AFIA has the ability to perform “AND logic gate” algorithm to eliminate false errors (artifacts) from the raw images to enhance accuracy of the MRI. We confirm the artifact filtering capability of AFIA in MRI phantoms and further demonstrate that artifact-free imaging of stem cell migration is possible in vivo.

The purpose of the study was to assess the usefulness of slice encoding for metal artifact correction (SEMAC) in 3.0-T magnetic resonance (MR) in minimizing metallic artifacts in patients with spinal prostheses.Institutional review board approval and informed consent were obtained for this study. Twenty-seven spine MR scans were performed with metal artifact reduction SEMAC between May 2011 and July 2012 in patients with metallic devices. The MR scans were performed on a 3-T MR system (Achieva; Philips Healthcare, Best, the Netherlands) including SEMAC-corrected T2-weighted axial/sagittal images and two-dimensional fast spin echo (FSE) axial/sagittal images. The SEMAC-corrected images were compared to conventional T2-weighted FSE images. Two musculoskeletal radiologists qualitatively analyzed the images in terms of visualization of the pedicle, vertebral body, dural sac, intervertebral disc, intervertebral neural foramina, screws and metallic artifacts. The paired images were rated using a 5-point scale. P values less than .05 were considered to indicate statistically significant differences.The SEMAC-corrected MR images significantly reduced the metal-related artifacts. The T2-weighted images with SEMAC sequences enabled significantly improved periprosthetic visualizations of the pedicle, vertebral body, dural sac and neural foramina, with the exception of the intervertebral disc (P.05). In addition, there was significant improvement in prosthesis visualization (P.05).MR images with SEMAC can reduce metal-related artifacts, providing improved delineation of the prosthesis and periprosthetic region. However, for the evaluation of the intervertebral disc, the SEMAC-corrected MR images showed no significant benefits.

Purpose The purpose of the study was to validate the diagnostic performance of high-resolution isovolumetric magnetic resonance arthrography (MRA) for intrinsic ligament and triangular fibrocartilage complex (TFCC) tears of the wrist as compared to conventional MR imaging (MRI). Materials and methods Forty-eight patients with traumatic TFCC tears at arthroscopy were enrolled. All patients had underwent proton-density- and T2-weighted MRI before arthrography and three-dimensional T1 high-resolution isovolumetric examination (3D-THRIVE) MRA on a 3-T MR. We assessed the presence of scapholunate interosseous ligament (SLIL)/lunotriquetral interosseous ligament (LTIL) or TFCC tears using the arthroscopy as a gold standard. Results Arthroscopy revealed 37 TFCC central tears, 15 TFCC peripheral tears, 20 SLIL tears and 13 LTIL tears. Sensitivities of MRI and MRA were 70.3% and 94.6% for detection of TFCC central tears, 60.0% and 93.3% for detection of TFCC peripheral tears, 65.0% and 85.0% for SLIL tears, and 61.5% and 84.6% for LTIL tears. The specificity of the MRI was 100% for the detection of ligaments and TFCC tears. The specificities of the MRA for detection of TFCC central tears, TFCC peripheral tears, SLIL tears and LTIL tears were 100%, 97%, 96.4% and 100%, respectively. Conclusion Isovolumetric 3D-THRIVE wrist MRA provided better results for depiction of intrinsic ligament and TFCC tears than wrist MRI.

Comparison between YazooÂŽ and Seoul Strawberry MilkÂŽ. (DOCX 38 kb)

Weights of animals between groups during the tasks. a. Average weight of animals during the unrestricted FR5 and PR4 schedules (one-way ANOVA; FR, F = 1.62, df = 2,11, p = 0.24; PR, F = 0.96, df = 2,11, p = 0.412). n = 4-7 per group. b. Average weight of animals between the UK and Korea during the probe session of 5-CSRTT (t = 5.98, df = 29, *p < 0.001). FR, fixed-ratio; PR, progressive-ratio; 5-CSRTT, 5-choice serial reaction time task; LM, low-fat milk; SM, strawberry-flavored milk; PM, plain white milk; YZ, Yazoo® strawberry milkshake (UK cohort); SS, Seoul Strawberry milk® (Korea cohort). n = 15-16 per group. Error bar indicates mean ± SE. Figure S2. Accumulated number of sessions required in each stage of FR training. The accumulated number of sessions required to reach the criterion in each stage of FR training revealed significantly reduced speed of learning in LM condition than other conditions (mixed-effect model; main effect of reinforcer, F = 11.3, df = 2,12, p = 0.002; main effect of stage, F = 219.4, df = 3,36, p < 0.0001; reinforcer by stage interaction, F = 33.2, df = 6,36, p < 0.0001). FR, fixed-ratio; LM, low-fat milk; SM, strawberry-flavored milk; PM, plain white milk. n = 4-7 per group. Error bar indicates mean ± SE. *p < 0.05, ***p < 0.0001 in simple main effect of reinforcer at each stage. (DOCX 1595 kb)

Patient Male, 59 FINAL DIAGNOSIS: Xanthogranulomatous osteomyelitis Symptoms: Painful swelling in the wrist Medication: Drug history of antifulgal agents Clinical Procedure: Excisional biopsy Specialty: Radiology. Objective Rare disease. Background Xanthogranulomatous inflammation is a chronic inflammatory disease in which bone involvement is extremely rare. Bone involvement of xanthogranulomatous inflammation, termed xanthogranulomatous osteomyelitis (XO), often presents as a mass-like lesion extending to adjacent structures, which can mimic infiltrative carcinoma. Case report We present a case of XO in the ulna, which mimicked a neoplasm. A 59-year-old man presented with a 2-month history of painful swelling in the right wrist. Plain radiography and CT showed an osteolytic lesion at the distal ulna. MRI revealed a soft-tissue mass with lobulated margins and contrast enhancement. Intense uptake in bone scan and PET suggested malignancy. An excisional biopsy from the representative area resulted in a pathology diagnosis of XO. Conclusions Gross and radiologic manifestations of XO can mimic neoplasm. XO generally has benign prognosis, contrary to malignant bone tumor. Therefore, biopsy and histopathological confirmation are necessary for proper management.

Objective To evaluate the feasibility of synthetic magnetic resonance imaging (MRI) compared to conventional MRI for the diagnosis of internal derangements of the knee at 3T. Materials and methods Following Institutional Review Board approval, image sets of conventional and synthetic MRI in 39 patients were included. Two musculoskeletal radiologists compared the image sets and qualitatively analyzed the images. Subjective image quality was assessed using a four-grade scale. Interobserver agreement and intersequence agreement between conventional and synthetic images for cartilage lesions, tears of the cruciate ligament, and tears of the meniscus were independently assessed using Kappa statistics. In patients who underwent arthroscopy (n = 8), the sensitivity, specificity, and accuracy for evaluated internal structures were calculated using arthroscopic findings as the gold standard. Results There was no statistically significant difference in image quality (p = 0.90). Interobserver agreement (κ = 0.649- 0.981) and intersequence agreement (κ = 0.794-0.938) were nearly perfect for all evaluated structures. The sensitivity, specificity, and accuracy for detecting cartilage lesions (sensitivity, 63.6% vs. 54.6-63.6%; specificity, 91.9% vs. 91.9%; accuracy, 83.3-85.4% vs. 83.3-85.4%) and tears of the cruciate ligament (sensitivity, specificity, accuracy, 100% vs. 100%) and meniscus (sensitivity, 50.0-62.5% vs. 62.5%; specificity, 100% vs. 87.5-100%; accuracy, 83.3-85.4% vs. 83.3-85.4%) were similar between the two MRI methods. Conclusion Conventional and synthetic MRI showed substantial to almost perfect degree of agreement for the assessment of internal derangement of knee joints. Synthetic MRI may be feasible in the diagnosis of internal derangements of the knee.

To optimize and investigate the influence of bipolar gradients for flow suppression in metabolic quantification of hyperpolarizedThe trade-off between the amount of flow suppression using bipolar gradients and T2* effect from static spins was simulated. A free induction decay CSI sequence with alternations between the flow-suppressed and non-flow-suppressed acquisitions for each repetition time was developed and was applied to liver tumor-bearing mice via injection of hyperpolarized [1-The in vivo results from flow suppression using the velocity-optimized bipolar gradient were comparable with the simulation results. The vascular signal was adequately suppressed and signal loss in stationary tissue was minimized. Application of the velocity-optimized bipolar gradient to tumor-bearing mice showed reduction in the vessel-derived pyruvate signal contamination, and the average lactate/pyruvate ratio increased by 0.095 (P 0.05) in the tumor region after flow suppression.Optimization of the bipolar gradient is essential because of the short

An indirect method for in vivo T

Superparamagnetic iron oxide (SPIO) nanoparticles have been intensively investigated as MRI probes due to the noninvasive detection of in vivo pathological changes. In the study, a nanosized system for SPIO delivery to a tumor was prepared to overcome the common challenges of SPIO nanoparticles such as insufficient uptake of SPIO by specific cells due to instability, short half-life by macrophage, and low efficiency of internalization. SPIO with ca. 6 nm sizes as a MRI probe and PLA–PEG (5K–2K) as a biocompatible stable system were prepared. The hydrophobic modified SPIO were loaded into the core of micelles and showed a stable dispersion with 140–170 nm particle sizes. The SPIO loading micelles showed higher relaxivity coefficients and increases of T 2 relaxation in vivo MR imaging. This SPIO delivery system with high stability and sensitivity can be a promising imaging formulation as MRI T 2 probes for tumor detection.

Biocompatible polymers have been of considerable interest in developing drug delivery systems (DDSs). However, physicochemical characterizations of the polymers and DDSs had been limited because of the difficulty in obtaining the same synthesized copolymers and achieving a similar drug loading ability with the differing properties of the drugs. Therefore, a correlational study of the relationships between copolymers and DDSs was required to estimate the properties of the DDSs and to develop optimal systems of delivery depending on the drug. In this study, we presented several relationship correlation equations of physicochemical properties and copolymers according to their molecular weights (MWs) using amphiphilic block copolymers composed of poly(L-lactide)-block-methoxy-poly(ethylene glycol) (PLA-b-mPEG). The PLA-b-mPEG was characterized by nuclear magnetic resonance and gel permeation chromatography, and the critical micelle concentration (CMC), sizes, and drug loading capacity (DLC) of the self-assembling micelles from the copolymers with different MWs were all measured. The increase in MW of the PLA led to a decrease in CMC and DLC with an increase of the particle sizes. The relationship between the MW of the PLA and the physicochemical properties of the micelles demonstrated a good correlation, which provides excellent information for the use in the development of tailor-made DDSs based on copolymers pursuing optimal particle size, DLC, CMC, and so on. Open image in new window

The aims of this study were as follows: (1) to determine the dimensions of the posterior compartments and the location of the popliteal artery with regard to the posterior septum by magnetic resonance arthrography; (2) to assess the effect of demographic factors on the measurements taken; and (3) to find a safe means of establishing the transseptal portal. Thirty magnetic resonance arthrographies taken in 90° of flexion were evaluated to simulate knee position during arthroscopic surgery. Coronal and axial images were obtained in positions parallel and perpendicular to the long axis of the tibia, respectively. The anterior-to-posterior dimensions of the posteromedial and posterolateral compartments and popliteal artery locations were measured in the safe zone to establish transseptal portals. These dimensions were measured in axial images corresponding to the mid-PCL level. The average anterior-to-posterior dimension was 11.7 ± 2.9 mm in the posteromedial compartment versus 7.9 ± 1.8 mm in the posterolateral compartment. The anterior-to-posterior dimension was consistently greater in the posteromedial compartment, and the average ratio of the two dimensions was 1.5 ± 0.3. The average posterior deviation of the popliteal artery from the PCL was 27.1 ± 4.8 mm. The popliteal artery was always located lateral to the septum, and the lateral deviation on averaged measured 10.2 ± 4.0 mm. The safe margin of the posteromedial compartment is consistently wider than that of the posterolateral compartment, and the popliteal artery is consistently located lateral to the posterior septum. Therefore, injury to the popliteal artery can be avoided when penetrating the septum lateral to medial direction, even if the penetrating stick slips posteriorly. Diagnostic study, Level IV.