Relationship between assistant's lens exposure and dose information during computed tomography examinations.

According to International Commission of Radiological Protection, the equivalent dose limit for the eye lens for occupational exposure is recommended to be 20 mSv yr-1, averaged over 5 years, with no single year above 50 mSv. Some studies reported the measurement of assistant's lens exposure in diagnostic computed tomography (CT) examinations, but further investigation is still required in the association between the lens dose for assistants and various dose parameters. Therefore, we measured the assistant's lens exposure using small optically stimulated luminescence dosimeters. The type of occupation, type of assistance, total scan time, total mAs, total scan length, and dose-length product (DLP) were recorded and analyzed in association with air kerma at the lens position. The assistance was classified into four types: 'assisted ventilation,' 'head holding,' 'body holding,' and 'raising patient's arm.' The air kerma of lens position was not significantly different for each assistance type (p< 0.05, Kruskal-Wallis test). Further, the lens doses for assistants correlated with DLP, but with various strengths of correlation with the assistance type and were influenced by the distance from the CT gantry. In conclusion, lens dose during assistance and DLP demonstrated the strongest correlation. 'Raising patient's arm' and 'head holding' exhibited stronger correlations, which required less table movement during the CT scan than 'assisted ventilation' and 'body holding'.

A novel simultaneous three-dimensional volumetric morphological imaging and T2-mapping method, multi-interleaved X-prepared turbo-spin echo with intuitive relaxometry provides more accurate quantification of cervical spinal nerves.

PURPOSE: MIXTURE is a simultaneous morphological and quantitative imaging sequence developed by Philips that provides high-resolution T2 maps from the imaged series. We aimed to compare the T2 maps of MIXTURE and SHINKEI-Quant (S-Q) in the cervical spine and to examine their usefulness in the functional diagnosis of cervical radiculopathy. METHODS: Seven healthy male volunteers (mean age: 31 ± 8.0 years) and one patient with cervical disc herniation (44 years old, male) underwent cervical spine magnetic resonance imaging (MRI), and T2-mapping of each was performed simultaneously using MIXTURE and S-Q in consecutive sequences in one imaging session. The standard deviation (SD) of the T2 relaxation times and T2 relaxation times of the bilateral C6 and C7 dorsal root ganglia (DRG) and C5/6 level cervical cord on the same slice in the 3D T2-map of the cervical spine coronal section were measured and compared between MIXTURE and S-Q. RESULTS: T2 relaxation times were significantly shorter in MIXTURE than in S-Q for all C6, C7 DRG, and C5/6 spinal cord measurements. The SD values of the T2 relaxation times were significantly lower for MIXTURE in the C5/6 spinal cord and C7 DRG. In cervical disc herniation, MRI showed multiple intervertebral compression lesions with spinal canal stenosis at C5/6 and disc herniation at C6/7. CONCLUSION: MIXTURE is useful for preoperative functional diagnosis. T2-mapping using MIXTURE can quantify cervical nerve roots more accurately than the S-Q method and is expected to be clinically applicable to cervical radiculopathy.

A novel PET probe to selectively image heat shock protein 90α/ß isoforms in the brain.

BACKGROUND: Heat shock proteins (HSPs) are present throughout the brain. They function as molecular chaperones, meaning they help with the folding and unfolding of large protein complexes. These chaperones are vital in the development of neuropathological conditions such as Alzheimer's disease and Lewy body disease, with HSP90, a specific subtype of HSP, playing a key role. Many studies have shown that drugs that inhibit HSP90 activity have beneficial effects in the neurodegenerative diseases. Therefore, HSP90 PET imaging ligand can be used effectively to study HSP90 in neurodegenerative diseases. Among four HSP90 isoforms, two cytosolic isoforms (HSP90α and HSP90ß) thought to be involved in the structural homeostasis of the proteins related to the neurodegenerative diseases. Currently, no useful PET imaging ligands selectively targeting the two cytosolic isoforms of HSP90 have been available yet. RESULTS: In this study, we developed a novel positron emission tomography (PET) imaging ligand, [11C]BIIB021, by 11C-radiolabeling (a positron emitter with a half-life of 20.4 min) 6-Chloro-9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine (BIIB021), an inhibitor with a high affinity for and selectivity to HSP90α and HSP90ß. [11C]BIIB021 was synthesized with a high yield, molar activity and radiochemical purity. [11C]BIIB021 showed a high binding affinity for rat brain homogenate as well as human recombinant HSP90α and HSP90ß proteins. Radioactivity was well detected in the rat brain (SUV 1.4). It showed clear specific binding in PET imaging of healthy rats and autoradiography of healthy rat and human brain sections. Radiometabolite was detected in the brain, however, total distribution volume was well quantified using dual-input graphical model. Inhibition of p-glycoprotein increased brain radioactivity concentrations. However, total distribution volume values with and without p-glycoprotein inhibition were nearly the same. CONCLUSIONS: We have developed a new PET imaging agent, [11C]BIIB021, specifically targeting HSP90α/ß. We have been successful in synthesizing [11C]BIIB021 and in vitro and in vivo imaging HSP90α/ß. However, the quantification of HSP90α/ß is complicated by the presence of radiometabolites in the brain and the potential to be a substrate for p-glycoprotein. Further efforts are needed to develop radioligand suitable for imaging of HSP90α/ß.

Strong Diagnostic Performance of Single Energy 256-row Multidetector Computed Tomography with Deep Learning Image Reconstruction in the Assessment of Myocardial Fibrosis.

Objective Although magnetic resonance imaging (MRI) is the gold standard for evaluating abnormal myocardial fibrosis and extracellular volume (ECV) of the left ventricular myocardium (LVM), a similar evaluation has recently become possible using computed tomography (CT). In this study, we investigated the diagnostic accuracy of a new 256-row multidetector CT with a low tube-voltage single energy scan and deep-learning-image reconstruction (DLIR) in detecting abnormal late enhancement (LE) in LVM. Methods We evaluated the diagnostic performance of CT for detecting LE in LVM and compared the results with those of MRI as a reference. We also measured the ECV of the LVM on CT and compared the results with those on MRI. Patients or Materials We analyzed 50 consecutive patients who underwent cardiac CT, including a late-phase scan and MRI, within three months of suspected cardiomyopathy. All patients underwent 256-slice CT (Revolution CT Apex; GE Healthcare) with a low tube-voltage (70 kV) single energy scan and DLIR for a late-phase scan. Results In patient- and segment-based analyses, the sensitivity, specificity, and accuracy of detection of LE on CT were 94% and 85%, 100% and 95%, and 96% and 93%, respectively. The ECV of LVM per patient on CT and MRI was 33.0% ±6.2% and 35.9% ±6.1%, respectively. These findings were extremely strongly correlated, with a correlation coefficient of 0.87 (p <0.0001). The effective radiation dose on late-phase scanning was 2.4±0.9 mSv. Conclusion The diagnostic performance of 256-row multislice CT with a low tube voltage and DLIR for detecting LE and measuring ECV in LVM is credible.

Discovery and SAR of JTE-151: A Novel RORγ Inhibitor for Clinical Development.

A number of RORγ inhibitors have been reported over the past decade. There were also several examples advancing to human clinical trials, however, none of them has reached the market yet, suggesting that there could be common obstacles for their future development. As was expected from the general homology of nuclear receptor ligands, insufficient selectivity as well as poor physicochemical properties were identified as potential risks for a RORγ program. Based on such considerations, we conducted a SAR investigation by prioritizing drug-like properties to mitigate such potential drawbacks. After an intensive SAR exploration with strong emphasis on "drug-likeness" indices, an orally available RORγ inhibitor, JTE-151, was finally generated and was advanced to a human clinical trial. The compound was confirmed to possess highly selective profiles along with good metabolic stability, and most beneficially, no serious adverse events (SAE) and good PK profiles were observed in the human clinical trial.

Noradrenaline transporter PET reflects neurotoxin-induced noradrenaline level decrease in the rat hippocampus.

BACKGROUND: The neuropathological changes of early Alzheimer's disease (AD) include neurodegenerative loss of noradrenaline neurons in the locus coeruleus with decreasing noradrenaline availability in their projection areas such as the hippocampus. This diminishing noradrenaline availability is thought to play an important role pathophysiologically in the development of cognitive impairment in AD, because noradrenaline is not only essential for maintaining cognitive functions such as memory, learning and attention, but also its anti-inflammatory action, where its lack is known to accelerate the progression of AD in the mouse model. Therefore, the availability of in vivo biomarkers of the integrity of noradrenaline neurons may be beneficial for furthering our understanding of the role played by the noradrenaline system in the progressive cognitive dysfunction seen in AD patients. In this study, we investigated if PET imaging of noradrenaline transporters can predict the level of noradrenaline in the brain. Our hypothesis was PET measured noradrenaline transporter densities could predict the level of noradrenaline concentrations in the rat hippocampus after lesioning of noradrenaline neurons in this region. RESULTS: We chemically lesioned the hippocampus of rats (n = 15) by administering a neurotoxin, DSP-4, in order to selectively damage axonal terminals of noradrenergic neurons. These rats then underwent PET imaging of noradrenaline transporters using [11C]MRB ((S,S)-[11C]Methylreboxetine). To validate our hypothesis, postmortem studies of brain homogenates of these rats were performed to measure both noradrenaline transporter and noradrenaline concentrations. [11C]MRB PET showed decreased noradrenaline transporter densities in a DSP-4 dose-dependent manner in the hippocampus of these rats. In turn, these PET measured noradrenaline transporter densities correlated very well with in vitro measured noradrenaline concentrations as well as in vitro transporter densities. CONCLUSIONS: [11C]MRB PET may be used as an in vivo biomarker of noradrenaline concentrations in the hippocampus of the neurodegenerating brain. Further studies appear warranted to extend its applicability to AD studies.

Structural Dissection of Epsin-1 N-Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature.

Spatiotemporal structural alterations in cellular membranes are the hallmark of many vital processes. In these cellular events, the induction of local changes in membrane curvature often plays a pivotal role. Many amphiphilic peptides are able to modulate membrane curvature, but there is little information on specific structural factors that direct the curvature change. Epsin-1 is a representative protein thought to initiate invagination of the plasma membrane upon clathrin-coated vesicles formation. Its N-terminal helical segment (EpN18) plays a key role in inducing positive membrane curvature. This study aimed to elucidate the essential structural features of EpN18 in order to better understand general curvature-inducing mechanisms, and to design effective tools for rationally controlling membrane curvature. Structural dissection of peptides derived from EpN18 revealed the decisive contribution of hydrophobic residues to (i) enhancing membrane interactions, (ii) helix structuring, (iii) inducing positive membrane curvature, and (iv) loosening lipid packing. The strongest effect was obtained by substitution with leucine residues, as this EpN18 analog showed a marked ability to promote the influx of octa-arginine cell-penetrating peptides into living cells.

Modulation of AMPK/ TET2/ 5-hmC axis in response to metabolic alterations as a novel pathway for obesity-related colorectal cancer development.

Obesity is a major risk factor for colorectal cancer (CRC). Sustained hyperglycemia destabilizes tumor suppressor ten-eleven translocation (TET) 2, which is a substrate of AMPK, thereby dysregulating 5-hydroxymethylcytosine (5-hmC). However, the role played by this novel pathway in the development of obesity-related CRC is unclear. In this study, we aimed to evaluate the expression levels of TET2 and 5-hmC in obesity-related CRC and the effects of TET2 expression on the proliferation of CRC cells. To this end, surgically resected CRC samples from seven obese patients (Ob-CRC) and seven non-obese patients (nOb-CRC) were analyzed, and expression levels of the TET family and 5-hmC were compared between the groups. A decrease was observed in TET2 mRNA levels and 5-hmC levels in Ob-CRC compared to that in nOb-CRC. Furthermore, we used CRC cell lines to investigate the relationship between insulin, proliferation, and TET expression and AMPK. In cell lines, glucose and insulin treatments suppressed the expression of TET2 and increased cell proliferation. Downregulation of TET2 using siRNA also induced cell proliferation. An AMPK activator inhibited insulin- or glucose-stimulated cell proliferation and restored TET2 expression. We propose the AMPK-TET2-5-hmC axis as a novel pathway and potential therapeutic target in obesity-related CRC development.

Evaluation of x-ray effective focal spot size dependency on x-ray exposure settings using edge response analysis.

The effective focal spot size of x-ray tubes is one of the major factors that substantially affect the resultant x-ray images, and it is known to be dependent on the x-ray exposure setting used. This study aims to evaluate the relationship between the effective focal spot size and the tube current and voltage and assess its reproducibility among several x-ray tubes. The evaluation was performed using edge response analysis, in which a 1-mm thick tungsten edge was projected onto a flat panel detector with a magnification factor of 2. The edge image was then differentiated to obtain the line spread function, followed by a detector blur-removing process through Fourier analysis to obtain the true focus profile. The resultant focal spot size increased as the tube current increased, whereas it decreased as the tube voltage increased, as expected. The rate of change was similar along the width and the length directions, while the small focus changed more significantly than the large focus. The reproducibility among four x-ray tubes of the same model was excellent as the maximum variation < 20%. In conclusion, the edge response method can provide useful information on the x-ray focal spot relationship with the x-ray exposure settings used, as well as its reproducibility among several x-ray tubes.

Linked color imaging improves the diagnostic accuracy of eosinophilic esophagitis.

Objectives: To assess the usefulness of linked color imaging (LCI), a recently developed image-enhanced endoscopy technique, in the endoscopic diagnosis of eosinophilic esophagitis (EoE). Methods: Thirty white light images (WLIs) and 30 WLI+LCI images collected from patients with and without EoE were randomly and blindly reviewed by 10 endoscopists, including four experts (Exs) and six non-Exs. Edema, ring, exudate furrows, and strictures were rated on the adjusted EoE endoscopic reference score; the diagnosis of EoE was assessed. Using the kappa value, inter- and intra-observer agreements were analyzed among endoscopists. Results: WLI+LCI images had a higher diagnostic accuracy for EoE than WLIs (0.85 vs. 0.70, respectively), especially in non-Exs or endoscopists with no experience with EoE patients. Inter-observer agreement for WLI+LCI images statistically surpassed WLIs for furrows (kappa, 0.73 vs. 0.67, respectively; p = 0.0013), stricture (kappa, 0.51 vs. 0.39, respectively; p = 0.0072), and diagnosis (kappa, 0.67 vs. 0.57, respectively; p < 0.0001) of EoE. The increase in inter-observer agreement in WLI+LCI images allowed for a reduction in the differences between the Exs and non-Ex endoscopists. Intra-observer agreement for WLI+LCI images surpassed WLIs for a ring (kappa, 0.62 vs. 0.43, p = 0.0052), and a similar trend was found in exudates, furrows, and diagnosis irrespective of the Exs or non-Exs. Conclusions: LCI can contribute to the improvement of the endoscopic diagnosis for EoE, with "moderate" to "substantial" consistency, by enhancing the visibility of abnormal findings, leading to reduced diagnostic disparities among endoscopists.

Methyl 1-(4-fluoro-benz-yl)-1H-indazole-3-carboxyl-ate.

The title compound, C16H13FN2O2, was synthesized by nucleophilic substitution of the indazole N-H hydrogen atom of methyl 1H-indazole-3-carboxyl-ate with 1-(bromo-meth-yl)-4-fluoro-benzene. In the crystal, some hydrogen-bond-like inter-actions are observed.

Usefulness of a lead-acrylic shield for reducing lens dose of assistant in x-ray CT examination.

In computed tomography (CT) examinations, the usefulness of protective glasses for reducing lens exposure to assistants has been reported. The present study aimed to compare the dose reduction effect for assistants with lead-acrylic shields and protective glasses (0.07 mm Pb, 0.5 mm Pb) during CT examination. The air dose distribution in a CT examination room with and without a lead-acrylic shield was compared. It was found that the amount of scattered radiation was significantly reduced by installing a lead-acrylic shield at the CT gantry aperture. Moreover, the reduction rate of air kerma at the assistant's lens was higher using the lead acrylic shield than with the protective glasses-95.7% during head holding and 76.1% during assisted ventilation.

Usefulness of Simultaneous Magnetic Resonance Neurography and Apparent T2 Mapping for the Diagnosis of Cervical Radiculopathy.

STUDY DESIGN: Retrospective observational study. PURPOSE: We investigated the correlation between T2 relaxation times and clinical symptoms in patients with cervical radiculopathy caused by cervical disk herniation. OVERVIEW OF LITERATURE: There are currently no imaging modalities that can assess the affected cervical nerve roots quantitatively. METHODS: A total of 14 patients with unilateral radicular symptoms and five healthy subjects were subjected to simultaneous apparent T2 mapping and neurography with nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement signaling (SHINKEI-Quant) using a 3-Tesla magnetic resonance imaging. The Visual Analog Scale (VAS) score for neck pain and upper arm pain was used to evaluate clinical symptoms. T2 relaxation times of the cervical dorsal root ganglia of the brachial plexus were measured bilaterally from C4 to C8 in patients with radicular symptoms and from C5 to C8 in healthy controls. The T2 ratio was calculated as the affected side to unaffected side. RESULTS: When comparing nerve roots bilaterally at each spinal level, no significant differences in T2 relaxation times were found between patients and healthy subjects. However, T2 relaxation times of nerve roots in the patients with unilateral radicular symptoms were significantly prolonged on the involved side compared with the uninvolved side (p<0.05). The VAS score for upper arm pain was not significantly correlated with the T2 relaxation times, but was positively correlated with the T2 ratio. CONCLUSIONS: In patients with cervical radiculopathy, the SHINKEI-Quant technique can be used to quantitatively evaluate the compressed cervical nerve roots. The VAS score for upper arm pain was positively correlated with the T2 ratio. This suggests that the SHINKEI-Quant is a potential tool for the diagnosis of cervical nerve entrapment.

Atypical jejunal follicular lymphoma with severe stricture.

The typical macroscopic appearance of gastrointestinal follicular lymphoma (FL) are multiple white granules or small white polyps, called multiple lymphomatous polyposis type, and subsequent mass lesions with or without ulceration; however, an ulcer type with a stricture is extremely rare. We report a case of a 79-year-old male with severe jejunal stricture due to FL with an uncommon chromosomal translocation t(2;18)(p12;q21). The patient was treated with jejunectomy subsequent rituximab monotherapy with a favorable response. The presence of the stricture made its endoscopic diagnosis confusing; however, it was certainly accompanied by the distinctive white granules on the surface of the tumor as seen in typical FL. With the possibility of an FL with stricture in mind, it is important to collect subtle endoscopic findings of the surrounding mucosa carefully, in order to arrive at an accurate endoscopic diagnosis and eventually to the proper therapeutic option.

Low serum pancreatic amylase levels as a novel latent risk factor for colorectal adenoma in non-alcohol drinkers.

BACKGROUND AND AIM: Obesity, insulin resistance, and metabolic alterations increase the risk of colorectal cancer and adenoma (CRA). Non-alcoholic fatty liver disease (NAFLD) or pancreatic disease (NAFPD) shares many risk factors with CRA that may have significant roles in its development; however, the relationship between CRA and NAFLD/NAFPD remains unclear. METHODS: This cross-sectional study recruited 712 eligible participants without current drinking who had undergone total colonoscopy as part of a health checkup. These participants were classified into a CRA group (n = 236) and a control group (n = 439), which consisted of individuals without CRA and a history of polyp resection. NAFLD and NAFPD were diagnosed based on abdominal ultrasonography findings. RESULTS: Non-alcoholic fatty liver disease was observed more frequently in individuals with CRA than in the control group (55.9% vs 41.6%, P < 0.01). There was no significant association between NAFPD and CRA; however, serum pancreatic amylase (P-amylase) levels were significantly lower in individuals with CRA. Although NAFLD was one of the factors increasing the presence of CRA (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.07-2.10), low P-amylase levels were significantly associated with the presence of CRA (OR, 1.73; 95% CI, 1.04-2.88) independent of age, sex, current smoking, obesity, metabolic alterations including insulin resistance, and NAFLD. CONCLUSIONS: Low serum P-amylase levels were a possible independent risk factor for CRA in the present study. The latent pancreatic exocrine-endocrine-gut relationship was considered a novel pathway involved in obesity-related CRA development, in non-alcoholic individuals.

The Quantity and Quality of Lumbar Muscles and Lumbopelvic Parameters in Patients With Degenerative Spondylolisthesis.

Introduction Lumbar degenerative spondylolisthesis (DS) is one of the most common causes of low back pain. The lumbar muscles, such as the psoas major (PM), erector spinae (ES), and multifidus (MF) muscles, play an important role in the stability and functional movement of the lumbar spine. The quantities and qualities of these muscles may be related to the occurrence of DS and lumbopelvic parameters, such as lumbar lordosis (LL) and sacral slope (SS). However,the influence of lumbar muscles on DS and lumbopelvic alignment is not well understood. Methods Patients with L4 DS (DS group, n=25) and without DS (non-DS group, n=25) were included. Using sagittal reconstructed CT images of patients who visited our hospital for reasons other than low back disorders, LL, upper lumbar lordosis ([ULL] L1-L4), lower lumbar lordosis ([LLL] L4-S1), and SS were examined. To evaluate the quantity and quality of lumbar muscles, the gross cross-sectional area (GCSA), functional cross-sectional area (FCSA), and fat infiltration (FI) of the PM, ES, and MF muscles were measured by CT images. The lumbopelvic parameters, FCSA, GCSA, and FI of lumbar muscles were compared between the two groups. Then, each lumbar muscle parameter was analyzed for correlation with DS and lumbopelvic parameters. Results DS patients displayed significantly greater ULL and lower FI of the PM and ES muscles than non-DS patients (p=0.0078, 0.031, and 0.010, respectively). The FI of the ES muscle was significantly correlated with the presence of DS (p=0.010). The FCSA of the ES and MF muscles and the GCSA of the MF muscle showed a significant correlation with LL and SS in the non-DS group (p<0.05), but not in the DS group.. Conclusion ULL was greater in L4 DS patients, possibly related to the better quality of the ES muscle. All DS patients showed mild (grade I) spondylolisthesis, suggesting the possibility that lumbar muscle quality is better in patients with mild DS than in those without DS. The ES and MF muscles may play an important role in maintaining the lumbar lordotic angle in non-DS patients but not in DS patients.

Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.

Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamous cell carcinoma (ESCC) tissues and adjacent non-neoplastic epithelium (NE), and immunohistochemical staining of the protein encoded by the target gene. All male patients (n = 117) were drinkers or smokers, whereas 45% of the female patients (n = 33) were not. Somatic variants were compared among three age-matched groups: 13 female ESCC patients with smoking and drinking habits (known-risk group, F-KR), 13 female ESCC patients without these habits (unknown-risk group, F-UR), and 27 males with ESCC and smoking and drinking habits (M-KR). In the NE, the frequencies of CDKN2A variants were significantly higher in F-UR than in F-KR and M-KR. In both ESCC and NE, p14ARF was significantly overexpressed in F-UR than in the other groups. In conclusion, CDKN2A might be important in ESCC development, independent of known risk factors.