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Background: Given that changes in brain water content are often correlated with disease, investigating water content non-invasively and in vivo could lead to a better understanding of the pathogenesis of several neurologic diseases., Purpose: To adapt a super-resolution-based technique, previously developed for humans, to the rat brain and report in vivo high-resolution (HR) water content maps in comparison with ex vivo wet/dry methods., Study Type: Prospective., Animal Model: Eight healthy male Wistar rats., Field Strength/sequence: 9.4-T, multi-echo gradient-echo (mGRE) sequence., Assessment: Using super-resolution reconstruction (SRR), a HR mGRE image (200 μm isotropic) was reconstructed from three low-resolution (LR) orthogonal whole-brain images in each animal, which was followed by water content mapping in vivo. The animals were subsequently sacrificed, the brains excised and divided into five regions (front left, front right, middle left, middle right, and cerebellum-brainstem regions), and the water content was measured ex vivo using wet/dry measurements as the reference standard. The water content values of the in vivo and ex vivo methods were then compared for the whole brain and also for the different regions separately., Statistical Tests: Friedman's non-parametric test was used to test difference between the five regions, and Pearson's correlation coefficient was used for correlation between in vivo and ex vivo measurements. A P-value <0.05 was considered statistically significant., Results: Water content values derived from in vivo MR measurements showed strong correlations with water content measured ex vivo at a regional level (r = 0.902). Different brain regions showed significantly different water content values. Water content values were highest in the frontal brain, followed by the midbrain, and lowest in the cerebellum and brainstem regions., Data Conclusion: An in vivo technique to achieve HR isotropic water content maps in the rat brain using SRR was adopted in this study. The MRI-derived water content values obtained using the technique showed strong correlations with water content values obtained using ex vivo wet/dry methods., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 1., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: Robustness of radiomic features in physiological tissue is an important prerequisite for quantitative analysis of tumor biology and response assessment. In contrast to previous studies which focused on different tumors with mostly short scan-re-scan intervals, this study aimed to evaluate the robustness of radiomic features in cancer-free patients and over a clinically encountered inter-scan interval., Materials and Methods: Patients without visible tumor burden who underwent at least two portal-venous phase dual energy CT examinations of the abdomen between May 2016 and January 2020 were included, while macroscopic tumor burden was excluded based upon follow-up imaging for all patients (≥3 months). Further, patients were excluded if no follow-up imaging was available, or if the CT protocol showed deviations between repeated examinations. Circular regions of interest were placed and proofread by two board-certified radiologists (4 years and 5 years experience) within the liver (segments 3 and 6), the psoas muscle (left and right), the pancreatic head, and the spleen to obtain radiomic features from normal-appearing organ parenchyma using PyRadiomics. Radiomic feature robustness was tested using the concordance correlation coefficient with a threshold of 0.75 considered indicative for deeming a feature robust., Results: In total, 160 patients with 480 repeated abdominal CT examinations (range: 2-4 per patient) were retrospectively included in this single-center, IRB-approved study. Considering all organs and feature categories, only 4.58 % (25/546) of all features were robust with the highest rate being found in the first order feature category (20.37 %, 22/108). Other feature categories (grey level co-occurrence matrix, grey level dependence matrix, grey level run length matrix, grey level size zone matrix, and neighborhood gray-tone difference matrix) yielded an overall low percentage of robust features (range: 0.00 %-1.19 %). A subgroup analysis revealed the reconstructed field of view and the X-ray tube current as determinants of feature robustness (significant differences in subgroups for all organs, p < 0.001) as well as the size of the region of interest (no significant difference for the pancreatic head with p = 0.135, significant difference with p < 0.001 for all other organs)., Conclusion: Radiomic feature robustness obtained from cancer-free subjects with repeated examinations using a consistent protocol and CT scanner was limited, with first order features yielding the highest proportion of robust features., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nils Große Hokamp: Research support, talk honoraria (Philips), consultancy (Bristol Myers Squibb); David Zopfs: Research support, talk honoraria (Philips); Kristina Sonnabend: Employee (Philips); Clemens Hentschke: Employee (Mint Medical GmbH); Bettina Baeßler: Speaker (Bayer Vital GmbH), founder and CEO of Lernrad GmbH; Liliana Lourenco Caldeira: Research support (Philips)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Positron emission tomography (PET) is currently considered the non-invasive reference standard for lymph node (N-)staging in lung cancer. However, not all patients can undergo this diagnostic procedure due to high costs, limited availability, and additional radiation exposure. The purpose of this study was to predict the PET result from traditional contrast-enhanced computed tomography (CT) and to test different feature extraction strategies., Methods: In this study, 100 lung cancer patients underwent a contrast-enhanced 18 F-fluorodeoxyglucose (FDG) PET/CT scan between August 2012 and December 2019. We trained machine learning models to predict FDG uptake in the subsequent PET scan. Model inputs were composed of (i) traditional "hand-crafted" radiomics features from the segmented lymph nodes, (ii) deep features derived from a pretrained EfficientNet-CNN, and (iii) a hybrid approach combining (i) and (ii)., Results: In total, 2734 lymph nodes [555 (20.3%) PET-positive] from 100 patients [49% female; mean age 65, SD: 14] with lung cancer (60% adenocarcinoma, 21% plate epithelial carcinoma, 8% small-cell lung cancer) were included in this study. The area under the receiver operating characteristic curve (AUC) ranged from 0.79 to 0.87, and the scaled Brier score (SBS) ranged from 16 to 36%. The random forest model (iii) yielded the best results [AUC 0.871 (0.865-0.878), SBS 35.8 (34.2-37.2)] and had significantly higher model performance than both approaches alone (AUC: p < 0.001, z = 8.8 and z = 22.4; SBS: p < 0.001, z = 11.4 and z = 26.6, against (i) and (ii), respectively)., Conclusion: Both traditional radiomics features and transfer-learning deep radiomics features provide relevant and complementary information for non-invasive N-staging in lung cancer.

Supervised methods, such as those utilized in classification, prediction, and segmentation tasks for medical images, experience a decline in performance when the training and testing datasets violate the i.i.d (independent and identically distributed) assumption. Hence we adopted the CycleGAN(Generative Adversarial Networks) method to cycle training the CT(Computer Tomography) data from different terminals/manufacturers, which aims to eliminate the distribution shift from diverse data terminals. But due to the model collapse problem of the GAN-based model, the images we generated suffer serious radiology artifacts. To eliminate the boundary marks and artifacts, we adopted a score-based generative model to refine the images voxel-wisely. This novel combination of two generative models makes the transformation between diverse data providers to a higher fidelity level without sacrificing any significant features. In future works, we will evaluate the original datasets and generative datasets by experimenting with a broader range of supervised methods.

Positron emission tomography (PET) imaging with radiotracers that bind to fibrillary amyloid β (Aβ) deposits is an important tool for the diagnosis of Alzheimer's disease (AD) and for the recruitment of patients into clinical trials. However, it has been suggested that rather than the fibrillary Aβ deposits, it is smaller, soluble Aβ aggregates that exert a neurotoxic effect and trigger AD pathogenesis. The aim of the current study is to develop a PET probe that is capable of detecting small aggregates and soluble Aβ oligomers for improved diagnosis and therapy monitoring. An 18 F-labeled radioligand was prepared based on the Aβ-binding d-enantiomeric peptide RD2, which is currently being evaluated in clinical trials as a therapeutic agent to dissolve Aβ oligomers. 18 F-labeling was carried out using palladium-catalyzed S-arylation of RD2 with 2-[ 18 F]fluoro-5-iodopyridine ([ 18 F]FIPy). Specific binding of [ 18 F]RD2-cFPy to brain material from transgenic AD (APP/PS1) mice and AD patients was demonstrated with in vitro autoradiography. In vivo uptake and biodistribution of [ 18 F]RD2-cFPy were evaluated using PET analyses in wild-type and transgenic APP/PS1 mice. Although brain penetration and brain wash-out kinetics of the radioligand were low, this study provides proof of principle for a PET probe based on a d-enantiomeric peptide binding to soluble Aβ species., Competing Interests: Declaration of Competing Interest A.W. and D.W. are co-founders of Priavoid GmbH, Düsseldorf, Germany. A.W. is a part-time employee, and D.W. is a member of the supervisory board of Priavoid, which develops RD2 as a therapeutic compound. Priavoid holds no intellectual property concerning the development of RD2 as a diagnostic compound. All other authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

ClC-3 Cl - /H + exchangers are expressed in multiple endosomal compartments and likely modify intra-endosomal pH and [Cl - ] via the stoichiometrically coupled exchange of two Cl - ions and one H + . We studied pain perception in Clcn3 -/- mice and found that ClC-3 not only modifies the electrical activity of peripheral nociceptors but is also involved in inflammatory processes in the spinal cord. We demonstrate that ClC-3 regulates the number of Na v and K v ion channels in the plasma membrane of dorsal root ganglion (DRG) neurons and that these changes impair the age-dependent decline in excitability of sensory neurons. To distinguish the role of ClC-3 in Cl - /H + exchange from its other functions in pain perception, we used mice homozygous for the E281Q ClC-3 point mutation ( Clcn3 E281Q/E281Q ), which completely eliminates transport activity. Since ClC-3 forms heterodimers with ClC-4, we crossed these animals with Clcn4 -/- to obtain mice completely lacking in ClC-3-associated endosomal chloride-proton transport. The electrical properties of Clcn3 E281Q/E281Q /Clcn4 -/- DRG neurons were similar to those of wild-type cells, indicating that the age-dependent adjustment of neuronal excitability is independent of ClC-3 transport activity. Both Clcn3 -/- and Clcn3 E281Q/E281Q / Clcn4 -/- animals exhibited microglial activation in the spinal cord, demonstrating that competent ClC-3 transport is needed to maintain glial cell homeostasis. Our findings illustrate how reduced Cl - /H + exchange contributes to inflammatory responses and demonstrate a role for ClC-3 in the homeostatic regulation of neuronal excitability beyond its function in endosomal ion balance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sierra-Marquez, Willuweit, Schöneck, Bungert-Plümke, Gehlen, Balduin, Müller, Lampert, Fahlke and Guzman.)

Alzheimer's disease (AD) is characterized by formation of amyloid plaques and neurofibrillary tangles in the brain, which can be mimicked by transgenic mouse models. Here, we report on the characterization of amyloid load in the brains of two transgenic amyloidosis models using positron emission tomography (PET) with florbetaben (FBB), an 18 F-labeled amyloid PET tracer routinely used in AD patients. Young, middle-aged, and old homozygous APP/PS1 mice (ARTE10), old hemizygous APPswe/PS1ΔE9, and old wild-type control mice were subjected to FBB PET using a small animal PET/computed tomography scanner. After PET, brains were excised, and ex vivo autoradiography was performed. Plaque pathology was verified on brain sections with histological methods. Amyloid plaque load increased progressively with age in the cortex and hippocampus of ARTE10 mice, which could be detected with both in vivo FBB PET and ex vivo autoradiography. FBB retention showed significant differences to wild-type controls already at 9 months of age by both in vivo and ex vivo analyses. An excellent correlation between data derived from PET and autoradiography could be obtained ( r Pearson = 0.947, p < 0.0001). Although amyloid load detected by FBB in the brains of old APPswe/PS1ΔE9 mice was as low as values obtained with young ARTE10 mice, statistically significant discrimination to wild-type animals was reached ( p < 0.01). In comparison to amyloid burden quantified by histological analysis, FBB retention correlated best with total plaque load and number of congophilic plaques in the brains of both mouse models. In conclusion, the homozygous ARTE10 mouse model showed superior properties over APPswe/PS1ΔE9 mice for FBB small animal amyloid PET imaging. The absolute amount of congophilic dense-cored plaques seems to be the decisive factor for feasibility of amyloidosis models for amyloid PET analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Willuweit, Schöneck, Schemmert, Lohmann, Bremen, Honold, Burda, Jiang, Beer, Ermert, Willbold, Shah and Langen.)

Understanding the physiopathology of Alzheimer's disease (AD) has improved substantially based on studies of mouse models mimicking at least one aspect of the disease. Many transgenic lines have been established, leading to amyloidosis but lacking neurodegeneration. The aim of the current study was to generate a novel mouse model that develops neuritic plaques containing the aggressive pyroglutamate modified amyloid-β (pEAβ) species in the brain. The TAPS line was developed by intercrossing of the pEAβ-producing TBA2.1 mice with the plaque-developing line APPswe/PS1ΔE9. The phenotype of the new mouse line was characterized using immunostaining, and different cognitive and general behavioral tests. In comparison to the parental lines, TAPS animals developed an earlier onset of pathology and increased plaque load, including striatal pEAβ-positive neuritic plaques, and enhanced neuroinflammation. In addition to abnormalities in general behavior, locomotion, and exploratory behavior, TAPS mice displayed cognitive deficits in a variety of tests that were most pronounced in the fear conditioning paradigm and in spatial learning in comparison to the parental lines. In conclusion, the combination of a pEAβ- and a plaque-developing mouse model led to an accelerated amyloid pathology and cognitive decline in TAPS mice, qualifying this line as a novel amyloidosis model for future studies.

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1 H (400 MHz) and inner low-pass coil for 23 Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than -13.7 dB for 1 H and -27 dB for 23 Na. Signal-to-noise ratios (SNRs) were calculated and 23 Na flip angle maps were acquired. 23 Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo 1 H and 23 Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23 Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Positron emission tomography (PET) using O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of (18)F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy., Methods: F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10-11 days of tumor growth, the animals underwent dynamic PET after injection of (18)F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of (18)F-FET uptake (18-61 min p.i.) and the slope of the time-activity-curves (TAC) (18-61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC)., Results: The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7 ± 2.8 %; p < 0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r = 0.77; p < 0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (-8.2 ± 6.1 %; p < 0.03), but did not influence the slope of the tumor TAC., Conclusion: TBR of (18)F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation.

A measurement system for quantitative determination of both surface and bulk contributions to the photo-thermal absorption in DUV optics was developed. It is based upon a Hartmann-Shack wavefront sensor with a sensitivity of ~λ/10000 rms, accomplishing precise on-line monitoring of wavefront deformations of a collimated test laser beam transmitted perpendicular through the excimer laser-irradiated site of a cuboid sample. Caused by the temperature dependence of the refractive index as well as thermal expansion, the initially plane wavefront of the test laser is distorted into a cylindrical shape, with bending ends towards the surface. Sign and magnitude depend on index change and expansion. By comparison with thermal theory, this transient wavefront distortion yields a quantitative absolute measure of bulk and surface absorption losses in the sample. First rresults for fused silica are presented.