Characterization of carotid plaques using chemical exchange saturation transfer imaging.

PURPOSE: The preoperative assessment of carotid plaques is necessary to render revascularization safe and effective. The aim of this study is to evaluate the usefulness of chemical exchange saturation transfer (CEST)-MRI, particularly amide proton transfer (APT) imaging as a preoperative carotid plaque diagnostic tool. METHODS: We recorded the APT signal intensity on concentration maps of 34 patients scheduled for carotid endarterectomy. Plaques were categorized into group A (APT signal intensity ≥ 1.90 E-04; n = 12) and group B (APT signal intensity < 1.90 E-04; n = 22). Excised plaques were subjected to histopathological assessment and, using the classification promulgated by the American Heart Association, they were classified as intraplaque hemorrhage-positive [type VI-positive (tVI+)] and -negative [no intraplaque hemorrhage (tVI-)]. RESULTS: Of the 34 patients, 22 (64.7%) harbored tVI+- and 12 (35.3%) had tVI- plaques. The median APT signals were significantly higher in tVI+- than tIVI- patients (2.43 E-04 (IQR = 0.98-4.00 E-04) vs 0.54 E-04 (IQR = 0.14-1.09 E-04), p < .001). Histopathologically, the number of patients with tVI+ plaques was significantly greater in group A (100%, n = 12) than group B (45%, n = 22) (p < .01). The number of symptomatic patients or asymptomatic patients with worsening stenosis was also significantly greater in group A than group B (75% vs 36%, p < .01). CONCLUSION: In unstable plaques with intraplaque hemorrhage and in patients with symptoms or progressive stenosis, the ATP signals were significantly elevated. CEST-MRI studies has the potential for the preoperative assessment of the plaques' characteristics.

Conversion map from quantitative parameter mapping to myelin water fraction: comparison with R1·R2* and myelin water fraction in white matter.

OBJECTIVE: To clarify the relationship between myelin water fraction (MWF) and R1⋅R2* and to develop a method to calculate MWF directly from parameters derived from QPM, i.e., MWF converted from QPM (MWFQPM). MATERIALS AND METHODS: Subjects were 12 healthy volunteers. On a 3 T MR scanner, dataset was acquired using spoiled gradient-echo sequence for QPM. MWF and R1⋅R2* maps were derived from the multi-gradient-echo (mGRE) dataset. Volume-of-interest (VOI) analysis using the JHU-white matter (WM) atlas was performed. All the data in the 48 WM regions measured VOI were plotted, and quadratic polynomial approximations of each region were derived from the relationship between R1·R2* and the two-pool model-MWF. The R1·R2* map was converted to MWFQPM map. MWF atlas template was generated using converted to MWF from R1·R2* per WM region. RESULTS: The mean MWF and R1·R2* values for the 48 WM regions were 11.96 ± 6.63%, and 19.94 ± 4.59 s-2, respectively. A non-linear relationship in 48 regions of the WM between MWF and R1·R2* values was observed by quadratic polynomial approximation (R2 ≥ 0.963, P < 0.0001). DISCUSSION: MWFQPM map improved image quality compared to the mGRE-MWF map. Myelin water atlas template derived from MWFQPM may be generated with combined multiple WM regions.

Determination of Alzheimer's disease based on morphology and atrophy using machine learning combined with automated segmentation.

BACKGROUND: To evaluate the degree of cerebral atrophy for Alzheimer's disease (AD), voxel-based morphometry has been performed with magnetic resonance imaging. Detailed morphological changes in a specific tissue area having the most evidence of atrophy were not considered by the machine-learning technique. PURPOSE: To develop a machine-learning system that can capture morphology features for determination of atrophy of brain tissue in early-stage AD and classification of healthy participants or patients. MATERIAL AND METHODS: Three-dimensional T1-weighted (3D-T1W) data were obtained from AD Neuroimaging Initiative (200 healthy controls and 200 patients with early-stage AD). Automated segmentation of 3D-T1W data was performed. Deep learning (DL) and support vector machine (SVM) were trained using 66-segmented volume values as input and AD diagnosis as output. DL was performed using 66 volume values or gray matter (GM) and white matter (WM) volume values. SVM learning was performed using 66 volume values and six regions with high variable importance. 3D convolutional neural network (3D-CNN) was trained using the segmented images. Accuracy and area under curve (AUC) were obtained. Variable importance was evaluated from logistic regression analysis. RESULTS: DL for GM and WM volume values, accuracy 0.6; SVM for all volume values, accuracy 0.82 and AUC 0.81; DL for all volume values, accuracy 0.82 and AUC 0.8; 3D-CNN using segmental images of the whole brain, accuracy 0.5 and AUC 0.51. SVM using volume values of six regions, accuracy 0.82; image-based 3D-CNN, highest accuracy 0.69. CONCLUSION: Our results show that atrophic features are more considerable than morphological features in the early detection of AD.

Differences between professionals in treatment planning for patients with stage III lung cancer using treatment-planning QA software.

Background: The quality of treatment planning for stage III non-small cell lung cancer varies within and between facilities due to the different professions involved in planning. Dose estimation parameters were calculated using a feasibility dose-volume histogram (FDVH) implemented in the treatment planning quality assurance software PlanIQ. This study aimed to evaluate differences in treatment planning between occupations using manual FDVH-referenced treatment planning to identify their characteristics. Materials and methods: The study included ten patients with stage III non-small cell lung cancer, and volumetric-modulated arc therapy was used as the treatment planning technique. Fifteen planners, comprising five radiation oncologists, five medical physicists, and five radiological technologists, developed treatment strategies after referring to the FDVH. Results: Medical physicists had a higher mean dose at D98% of the planning target volume (PTV) and a lower mean dose at D2% of the PTV than those in other occupations. Medical physicists had the lowest irradiation lung volumes (V5 Gy and V13 Gy) compared to other professions, and radiation oncologists had the lowest V20 Gy and mean lung dose. Radiological technologists had the highest irradiation volumes for dose constraints at all indexes on the normal lung volume. Conclusions: The quality of the treatment plans developed in this study differed between occupations due to their background expertise, even when an FDVH was used as a reference. Therefore, discussing and sharing knowledge and treatment planning techniques among professionals is essential to determine the optimal treatment plan for each facility and patient.

Development of Correction for Signal-to-Noise Ratio Using a T2* With Improved Phase Method.

OBJECTIVE: This study aims to improve the signal-to-noise ratio (SNR) of the phase image focusing T2 and to develop an improved phase (iPhase) image acquired high SNR. METHODS: The iPhase images of phantom and brain were acquired with multi-echo spoiled gradient-echo. The phantom component was a gadopentetate dimeglumine (Gd-DTPA) solution made of different concentrations (0.1, 0.5, and 1 wt%) and Gd-DTPA (0.1, 0.5, and 1 wt%) with agar (1.0 wt%). We applied the iPhase image to susceptibility weighed image (SWI) and evaluated SNR of SWI. RESULTS: In phantom study, SNRs of conventional SWI at each sample were 19.8, 15.7, 7.4, 20.0, 17.4, and 27.3, respectively. Signal-to-noise ratios of SWI derived from iPhase method were 29.5, 33.7, 21.7, 28.5, 24.3, and 14.7, respectively. Then, the SNR showed an improvement of 196% at maximum (for the Gd-DTPA 1 wt% sample). In healthy volunteer study, SWI derived from iPhase method had the good contrast between white matter and gray matter. CONCLUSIONS: The iPhase image was able to improve the phase SNR. Moreover, iPhase method makes it possible to obtain a high SNR image when applying to SWI.

Electronic Transitions in Conformationally Controlled Peralkylated Hexasilanes.

The photophysical properties of oligosilanes show unique conformational dependence due to σ-electron delocalization. The excited states of the SAS, AAS, and AEA conformations of peralkylated n-hexasilanes, in which the SiSiSiSi dihedral angles are controlled into a syn (S), anti (A), or eclipsed (E) conformation, were investigated by using UV absorption, magnetic circular dichroism (MCD), and linear dichroism spectroscopy. Simultaneous Gaussian fitting of all three spectra identified a minimal set of transitions and the wavenumbers, oscillator strengths, and MCD B terms in all three compounds. The results compare well with those obtained by using the symmetry-adapted-cluster configuration interaction method and almost as well with those obtained by time-dependent density functional theory with the PBE0 functional. The conformational dependence of the transition energies and other properties of free-chain permethylated n-hexasilane, n-Si6 Me14 , was also examined as a function of dihedral angles, and the striking effects found were attributed to avoided crossings between configurations of σσ* and σπ* character.

Low-Lying π* Resonances of Standard and Rare DNA and RNA Bases Studied by the Projected CAP/SAC-CI Method.

Low-lying π* resonance states of DNA and RNA bases have been investigated by the recently developed projected complex absorbing potential (CAP)/symmetry-adapted cluster-configuration interaction (SAC-CI) method using a smooth Voronoi potential as CAP. In spite of the challenging CAP applications to higher resonance states of molecules of this size, the present calculations reproduce resonance positions observed by electron transmission spectra (ETS) provided the anticipated deviations due to vibronic effects and limited basis sets are taken into account. Moreover, for the standard nucleobases, the calculated positions and widths qualitatively agree with those obtained in previous electron scattering calculations. For guanine, both keto and enol forms were examined, and the calculated values of the keto form agree clearly better with the experimental findings. In addition to these standard bases, three modified forms of cytosine, which serve as epigenetic or biomarkers, were investigated: formylcytosine, methylcytosine, and chlorocytosine. Last, a strong correlation between the computed positions and the observed ETS values is demonstrated, clearly suggesting that the present computational protocol should be useful for predicting the π* resonances of congeners of DNA and RNA bases.

Hydrodynamic Tail Vein Injection as a Simple Tool for Yielding Extended Transgene Expression in Solid Tumors.

Hydrodynamic tail vein injection was considered an in vivo transfection method that yields a higher level of gene expression mainly in the liver. This method has been applied to cancer gene therapy targeting both hepatic and non-hepatic cancers. However, intratumor transgene expression in non-hepatic tumors has not been well studied. In this study, we showed an extended transgene expression of ß-galactosidase (LacZ), a nonsecretory protein, in a subcutaneously implanted murine solid tumor following the hydrodynamic injection of plasmid DNA (LacZ pDNA). Our result may indicate that the hydrodynamic injection method is a powerful tool that can be used to gain transgene expression not only in the liver but also in solid tumors.

Knowledge-based model building for treatment planning for prostate cancer using commercial treatment planning quality assurance software tools.

This study devised a method to efficiently launch the RapidPlan model for volumetric-modulated arc therapy for prostate cancer in small- and medium-sized facilities using high-quality treatment plans with the PlanIQ software as a reference. Treatment plans were generated for 30 patients with prostate cancer to construct the RapidPlan model using PlanIQ as a reference. In the context of PlanIQ-referenced treatment planning, treatment plans were developed, such that the feasibility dose-volume histogram of each organ-at-risk fell within F ≤ 0.1. For validation of the RapidPlan model, treatment plans were formulated for 20 patients using both RapidPlan and PlanIQ, and the differences were evaluated. The results of RapidPlan model validity assessment revealed that the RapidPlan-produced treatment plans exhibited higher quality in 11 of 20 patients. No significant differences were found between the treatment plans. In conclusion, high-quality treatment plans formulated using PlanIQ as reference facilitated efficient implementation of RapidPlan modeling.

Simplified assessment for chemical exchanged saturation transfer (CEST) imaging: local offset frequency and CEST effect.

The aim of this study is to develop a novel phantom for the evaluation of clinical CEST imaging settings, e.g., B0 and B1 field inhomogeneities, CEST contrast, and post-processing. We made a phantom composed of two slice sections: a grid section for local offset frequency evaluation and a sample section for CEST effect evaluation using different concentrations of an egg white albumin solution. On a 3 Tesla MR scanner, a phantom study was performed using CEST imaging; the mean B1 amplitudes were set at 1.2 and 1.9 µT, and CEST images with and without B0 corrections were acquired. Next, region of interest (ROI) analysis was performed for each slice. Then, CEST images with and without B0 corrections were compared at each B1 amplitude. The B0 corrected Z-spectrums at each local region in the grid section showed a shifting of the curve bottom to 0 ppm. Z-spectrum at B1 = 1.9 µT showed a broader curve shape than that at 1.2 µT. Moreover, MTRasym values at 3.5 ppm for each albumin sample at B1 = 1.9 µT were about two times higher than those at 1.2 µT. Our phantom enabled us to evaluate and optimize B0 inhomogeneity and the CEST effect at the B1 amplitude.

A blurring correction method suitable to analyze quantitative x-ray images derived from energy-resolving photon counting detector.

Objective.The purpose of this study is to propose a novel blurring correction method that enables accurate quantitative analysis of the object edge when using energy-resolving photon counting detectors (ERPCDs). Although the ERPCDs have the ability to generate various quantitative analysis techniques, such as the derivations of effective atomic number (Zeff) and bone mineral density values, at the object edge in these quantitative images, accurate quantitative information cannot be obtained. This is because image blurring prevents the gathering of accurate primary x-ray attenuation information.Approach.We developed the following procedure for blurring correction. A 5 × 5 pixels masking region was set as the processing area, and the pixels affected by blurring were extracted from the analysis of pixel value distribution. The blurred pixel values were then corrected to the proper values estimated by analyzing minimum and/or maximum values in the set mask area. The suitability of our correction method was verified by a simulation study and an experiment using a prototype ERPCD.Main results. WhenZeffimage of aluminum objects (Zeff= 13) were analyzed without applying our correction method, regardless of raw data or correction data applying a conventional edge enhancement method, the properZeffvalues could not be derived for the object edge. In contrast, when applying our correction method, 82% of pixels affected by blurring were corrected and the properZeffvalues were calculated for those pixels. As a result of investigating the applicability limits of our method through simulation, it was proven that it works effectively for objects with 4 × 4 pixels or more.Significance. Our method is effective in correcting image blurring when the quantitative image is calculated based on multiple images. It will become an in-demand technology for putting a quantitative diagnosis into actual medical examinations.

Differences of white matter structure for diffusion kurtosis imaging using voxel-based morphometry and connectivity analysis.

Objectives: In a clinical study, diffusion kurtosis imaging (DKI) has been used to visualize and distinguish white matter (WM) structures' details. The purpose of our study is to evaluate and compare the diffusion tensor imaging (DTI) and DKI parameter values to obtain WM structure differences of healthy subjects. Methods: Thirteen healthy volunteers (mean age, 25.2 years) were examined in this study. On a 3-T MRI system, diffusion dataset for DKI was acquired using an echo-planner imaging sequence, and T1-weghted (T1w) images were acquired. Imaging analysis was performed using Functional MRI of the brain Software Library (FSL). First, registration analysis was performed using the T1w of each subject to MNI152. Second, DTI (eg, fractional anisotropy [FA] and each diffusivity) and DKI (eg, mean kurtosis [MK], radial kurtosis [RK], and axial kurtosis [AK]) datasets were applied to above computed spline coefficients and affine matrices. Each DTI and DKI parameter value for WM areas was compared. Finally, tract-based spatial statistics (TBSS) analysis was performed using each parameter. Results: The relationship between FA and kurtosis parameters (MK, RK, and AK) for WM areas had a strong positive correlation (FA-MK, R2 = 0.93; FA-RK, R2 = 0.89) and a strong negative correlation (FA-AK, R2 = 0.92). When comparing a TBSS connection, we found that this could be observed more clearly in MK than in RK and FA. Conclusions: WM analysis with DKI enable us to obtain more detailed information for connectivity between nerve structures. Advances in knowledge: Quantitative indices of neurological diseases were determined using segmenting WM regions using voxel-based morphometry processing of DKI images.

An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. OBJECTIVE: This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). METHODS: EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. RESULTS: This trial began data collection in September 2021 and is expected to be completed in October 2023. CONCLUSIONS: This study can provide useful data to understand the characteristics of EPI-589. TRIAL REGISTRATION: Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42032.

Quantitative parameter mapping of contrast agent concentration and relaxivity and brain tumor extracellular pH.

In clinical magnetic resonance imaging, gadolinium-based contrast agents are commonly used for detecting brain tumors and evaluating the extent of malignancy. We present a new method to evaluate relaxivity (r1) and contrast agent concentration separately in contrast-enhanced lesions using quantitative parameter mapping (QPM). Furthermore, we also aimed to estimate the extracellular pH (pHe) of tumor lesions. We demonstrated that it is possible to evaluate pathophysiological tumor changes due to therapeutic efficacy by measuring r1 in contrast-enhanced lesions. In this study, the primary brain tumor group showed significantly higher r1 values than other brain disease groups (P < 0.001). Moreover, mean pHe value showed a trend for tumor malignancy having a lower pHe value and primary brain tumor having a significantly lower pHe than other brain diseases (P < 0.001). Our results might suggest that QPM can separately quantify r1 and CA concentration in brain tumors and that pHe brain tumor mapping could serve as a tumor biomarker. In conclusion, our method has potential clinical applications for assessing the treatment effects.

Myelin-weighted imaging derived from quantitative parameter mapping.

PURPOSE: We developed a novel method which is applicable to visualize contrast according to myelin components in the human brain using relaxation time derived from quantitative parameter mapping magnetic resonance imaging (QPM-MRI). MATERIALS AND METHODS: Using healthy volunteer data (n = 10), we verified that our method demonstrated that the myelin-weighted contrast increased proportionally by products R1 and R2*, i.e., QPM-myelin-weighted image, in which modified T1-weighted/T2-weighted (T1w/T2w) ratio mapping method was applied. We compared measurement values in white matter (WM) and gray matter (GM) regions of the T1w/T2w ratio and R1·R2* product maps of healthy volunteers. Linear regression analysis between each value. Mann Whitney U test between WM and GM signals in each myelin map. In addition, Additionally, QPM-myelin-weighted image was applied to a 32-year-old female MS patient. RESULTS: Linear regression analysis showed a highly significant correlation between conventional T1w/T2w ratios and R1·R2* products derived from QPM (R = 0.73, P < 0.0001). Moreover, there is a significant difference between WM and GM structures in each myelin images (both, P < 0.0001). Additionally, in a clinical case, MS lesions enabled observation of not only MS plaques but also heterogeneous myelin signal loss associated with demyelination more clearly than T2w image and conventional T1w/T2w ratio image. CONCLUSION: Our myelin-weighted imaging technique using QPM may be useful for myelin visualization and is expected to become independent of measurement conditions due to having quantitative characteristics of QPM itself.

Daily Dietary Supplementation with Steamed Soybean Improves Muscle Volume and Strength in Healthy People Lacking Exercise.

Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise.

A novel algorithm for extracting soft-tissue and bone images measured using a photon-counting type X-ray imaging detector with the help of effective atomic number analysis.

Most of the objects targeted for X-ray examination are composed of soft-tissue and bone. We aimed to develop an algorithm for generating X-ray images which can give quantitative information of soft-tissue and bone using an energy-resolving photon-counting type imaging detector. We used polychromatic X-rays for analysis in which both the beam hardening effect and detector response were properly corrected and then succeeded in virtually treating the amount of measured X-ray attenuation as if it were measured using monochromatic X-rays.

Effective atomic number image determination with an energy-resolving photon-counting detector using polychromatic X-ray attenuation by correcting for the beam hardening effect and detector response.

In this study, we propose an effective atomic number (Zeff) determination method based on a photon-counting technique. The proposed method can correct for the beam hardening effect and detector response based on polychromatic X-rays to allow high accuracy material identification. To demonstrate the effectiveness of our method, the procedure was applied to X-ray images acquired by a prototype energy-resolving photon-counting detector and we obtained an Zeff image with accuracy of Zeff ± 0.5 regardless of the mass thickness.