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Standardized reporting of multiparametric prostate MRI (mpMRI) is widespread and follows international standards (Pi-RADS). However, quantitative measurements from mpMRI are not widely comparable. Although T2 mapping sequences can provide repeatable quantitative image measurements and extract reliable imaging biomarkers from mpMRI, they are often time-consuming. We therefore investigated the value of quantitative measurements on a highly accelerated T2 mapping sequence, in order to establish a threshold to differentiate benign from malignant lesions. For this purpose, we evaluated a novel, highly accelerated T2 mapping research sequence that enables high-resolution image acquisition with short acquisition times in everyday clinical practice. In this retrospective single-center study, we included 54 patients with clinically indicated MRI of the prostate and biopsy-confirmed carcinoma (n = 37) or exclusion of carcinoma (n = 17). All patients had received a standard of care biopsy of the prostate, results of which were used to confirm or exclude presence of malignant lesions. We used the linear mixed-effects model-fit by REML to determine the difference between mean values of cancerous tissue and healthy tissue. We found good differentiation between malignant lesions and normal appearing tissue in the peripheral zone based on the mean T2 value. Specifically, the mean T2 value for tissue without malignant lesions was (151.7 ms [95% CI: 146.9-156.5 ms] compared to 80.9 ms for malignant lesions [95% CI: 67.9-79.1 ms]; p < 0.001). Based on this assessment, a limit of 109.2 ms is suggested. Aditionally, a significant correlation was observed between T2 values of the peripheral zone and PI-RADS scores (p = 0.0194). However, no correlation was found between the Gleason Score and the T2 relaxation time. Using REML, we found a difference of -82.7 ms in mean values between cancerous tissue and healthy tissue. We established a cut-off-value of 109.2 ms to accurately differentiate between malignant and non-malignant prostate regions. The addition of T2 mapping sequences to routine imaging could benefit automated lesion detection and facilitate contrast-free multiparametric MRI of the prostate., Competing Interests: Declarations. Ethics Approval: For this IRB approved (No. 19-299), retrospective case-control study, the hospital's PACS was searched by an independent investigator for prostate MRIs between 08/2018 and 07/2019. Consent to Participate: For the retrospective case-control study, no consent to participate was needed. Consent to Publish: For the anonymized data, no consent to publish is needed. Competing Interests: R.S. and T.H. are employed by Siemens Healthineers. T.P. receives funding from Berlin Institute of Health (Advanced Clinician Scientist Grant, Platform Grant), Ministry of Education and Research (BMBF, 01KX2021 (RACOON), 01KX2121 („NUM 2.0“, RACOON), 68GX21001A, 01ZZ2315D), German Research Foundation (DFG, SFB 1340/2), European Union (H2020, CHAIMELEON: 952172, DIGITAL, EUCAIM:101100633) and reports research agreements (no personal payments, outside of submitted work) with AGO, Aprea AB, ARCAGY-GINECO, Astellas Pharma Global Inc. (APGD), Astra Zeneca, Clovis Oncology, Inc., Holaira, Incyte Corporation, Karyopharm, Lion Biotechnologies, Inc., MedImmune, Merck Sharp & Dohme Corp, Millennium Pharmaceuticals, Inc., Morphotec Inc., NovoCure Ltd., PharmaMar S.A. and PharmaMar USA, Inc., Roche, Siemens Healthineers, and TESARO Inc., and fees for a book translation (Elsevier B.V.). A.M.B.: Bayer, Guebert, Siemens Healthineers (Consulting fees and travel Support)., (© 2024. The Author(s).)

Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) opens new possibilities in multimodal multiparametric (m2p) image analyses. But even the simultaneous acquisition of positron emission tomography (PET) and magnetic resonance imaging (MRI) does not guarantee perfect voxel-by-voxel co-registration due to organs and distortions, especially in diffusion-weighted imaging (DWI), which would be, however, crucial to derive biologically meaningful information. Thus, our aim was to optimize fusion and voxel-wise analyses of DWI and standardized uptake values (SUVs) using a novel software for m2p analyses. Using research software, we evaluated the precision of image co-registration and voxel-wise analyses including the rigid and elastic 3D registration of DWI and [18F]-Fluorodeoxyglucose (FDG)-PET from an integrated PET/MR system. We analyzed DWI distortions with a volume-preserving constraint in three different 3D-printed phantom models. A total of 12 PET/MR-DWI clinical datasets (bronchial carcinoma patients) were referenced to the T1 weighted-DIXON sequence. Back mapping of scatterplots and voxel-wise registration was performed and compared to the non-optimized datasets. Fusion was rated using a 5-point Likert scale. Using the 3D-elastic co-registration algorithm, geometric shapes were restored in phantom measurements; the measured ADC values did not change significantly (F = 1.12, p = 0.34). Reader assessment showed a significant improvement in fusion precision for DWI and morphological landmarks in the 3D-registered datasets (4.3 ± 0.2 vs. 4.6 ± 0.2, p = 0.009). Most pronounced differences were noted for the chest wall ( p = 0.006), tumor ( p = 0.007), and skin contour ( p = 0.014). Co-registration increased the number of plausible ADC and SUV combinations by 25%. The volume-preserving elastic 3D registration of DWI significantly improved the precision of fusion with anatomical sequences in phantom and clinical datasets. The research software allowed for a voxel-wise analysis and visualization of [18F]FDG-PET/MR data as a "combined diffusivity-metabolic index" (cDMI). The clinical value of the optimized PET/MR biomarker can thus be tested in future PET/MR studies.

Aim: The purpose of this IRB-approved, retrospective study was to compare image quality between 2D and high-resolution 3D, T2-weighted (T2WI) magnetic resonance imaging (MRI) sequences and to investigate the additional value of ultra-high b-value diffusion-weighted imaging (DWI; b=2,000 mm/s 2 ) for both rectal cancer staging and evaluating treatment response., Materials and Methods: From 12 February to 24 August 2016, 26 consecutive patients (22 males, four females; mean age: 61.9±14.0 years) with histologically-proven rectal cancer. In total 31 examinations [12 prior to and 19 after chemoradiation (CRT)] were included. The patients underwent pelvic MRI on a 3.0-T scanner (Magnetom Skyra, Erlangen, Germany). Three radiologists (3, 4, and 5 years of experience in MRI, respectively) independently assessed all images and rated the image quality of DWI (b=800 mm/s 2 ), apparent diffusion coefficient map, DWI (b=2,000 mm/s 2 ), 3D sagittal T2WI, 3D axial T2WI, 2D sagittal T2WI, and 2D axial T2WI of each patient, respectively. In addition, signal intensity ratios (SIR) were calculated between rectal cancer and obturator internus muscle (background) in all patients after CRT on DWI (b=2,000 mm/s 2 ) and correlated with histopathological regression grade (RG)., Results: Tumor delineation was significantly better by 2D T2WI than 3D T2WI both before and after CRT (before CRT: Z=-3.2, p=0.02; after CRT: Z=-4.408, p<0.001; all: Z=-5.192; p<0.001) and was the preferred method, although image quality ratings were not significantly different (3D sagittal: 4.00±0.48; 2D sagittal: 4.03±0.34, p=0.713; 3D axial: 3.85±0.61, 2D axial: 3.78±0.64, p=0.537). Independent t-test showed significantly higher SIR between those with RG 1 or 2 (moderate response: mean score=2.02) and those with RG 3+4 (good response: mean score=0.8) (t=3.044, p=0.011). In those with RG 4 (complete response), SIR of b2000 was 0.946 compared to a 1.41 average of the whole cohort. In two patients, tumor was invisible on b2000 following CRT (RG 3 and 4, respectively). Interobserver agreement was mostly good (κ≥0.6) regarding image quality assessment, except for poor agreement (κ=0.4) in DWI (b2000) between the two less-experienced readers., Conclusion: In conclusion, 3D T2WI might be useful for evaluating response to neoadjuvant therapy in a comprehensive, cost-effective protocol, where 2D imaging seems to be preferable. In addition, DWI (b2000) may be beneficial in assessing both the primary and the residual tumor after CRT in rectal cancer and SIR may be helpful in assessing response to CRT., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Purpose: Conventional MR imaging typically yields normal images of the brain or indicates lesions in areas of high aquaporin expression in patients with neuromyelitis optica. Diffusional kurtosis imaging was applied in patients with neuromyelitis optica to determine whether this technique could detect alterations in diffusion and diffusional kurtosis parameters in normal-appearing white matter and to explore the relationship between diffusional kurtosis imaging and DTI parameters., Materials and Methods: Thirteen patients with neuromyelitis optica and 13 healthy controls underwent MR imaging of the brain with conventional and diffusional kurtosis imaging sequences. Tract-based spatial statistics and region-of-interest-based analyses were conducted to identify differences between patients with neuromyelitis optica and controls through conventional DTI and diffusional kurtosis imaging parameters. The parameters were correlated to determine the potential relationship between them., Results: Compared with healthy controls, several diffusional kurtosis imaging and DTI parameters were altered in various fiber tracts of patients with neuromyelitis optica (P < .05). A significant decrease (P < .05) in radial kurtosis was observed in the corpus callosum and anterior corona radiata and left optic radiation. Differences (P < .1) in mean kurtosis were found in patients with neuromyelitis optica. We found a negative correlation between diffusional kurtosis imaging (radial kurtosis, axial kurtosis, mean kurtosis) and the corresponding DTI parameters (radial diffusivity, axial diffusivity, mean diffusivity). Positive correlations were found for radial kurtosis and mean kurtosis with fractional anisotropy., Conclusions: This study demonstrated differences in conventional diffusion and diffusional kurtosis parameters, especially radial kurtosis, in the normal-appearing white matter of patients with neuromyelitis optica compared with healthy controls. Larger studies of patients with neuromyelitis optica should be performed to assess the potential clinical impact of these findings., (© 2014 by American Journal of Neuroradiology.)

Aim: To evaluate the impact of computed b = 1400 s/mm(2) (C-b1400) vs measured b = 1400 s/mm(2) (M-b1400) diffusion-weighted images (DWI) on lesion detection rate, image quality and quality of lesion demarcation using a modern 3T-MR system based on a small-field-of-view sequence (sFOV)., Methods: Thirty patients (PSA: 9.5 ± 8.7 ng/mL; 68 ± 12 years) referred for magnetic resonance imaging (MRI) of the prostate were enrolled in this study. All measurements were performed on a 3T MR system. For DWI, a single-shot EPI diffusion sequence (b = 0, 100, 400, 800 s/mm²) was utilized. C-b1400 was calculated voxelwise from the ADC and diffusion images. Additionally, M-b1400 was acquired for evaluation and comparison. Lesion detection rate and maximum lesion diameters were obtained and compared. Image quality and quality of lesion demarcation were rated according to a 5-point Likert-type scale. Ratios of lesion-to-bladder as well as prostate-to-bladder signal intensity (SI) were calculated to estimate the signal-to-noise-ratio (SNR)., Results: Twenty-four lesions were detected on M-b1400 images and compared to C-b1400 images. C-b1400 detected three additional cancer suspicious lesions. Overall image quality was rated significantly better and SI ratios were significantly higher on C-b1400 (2.3 ± 0.8 vs 3.1 ± 1.0, P < 0.001; 5.6 ± 1.8 vs 2.8 ± 0.9, P < 0.001). Comparison of lesion size showed no significant differences between C- and M-b1400 (P = 0.22)., Conclusion: Combination of a high b-value extrapolation and sFOV may contribute to increase diagnostic accuracy of DWI without an increase of acquisition time, which may be useful to guide targeted prostate biopsies and to improve quality of multiparametric MRI (mMRI) especially under economical aspects in a private practice setting.

The Tietê River and its tributary Pinheiros River receive a highly complex organic and inorganic pollutants load from sanitary sewage and industrial sources, as well as agricultural and agroindustrial activities. The aim of the present study was to evaluate the embryotoxic and teratogenic effects of sediments from selected locations in the Tietê River Basin by means of the sediment contact embryo toxicity assay with Danio rerio, in order to provide a comprehensive and realistic insight into the bioavailable hazard potential of these sediment samples. Lethal and sub-lethal effects were recorded, and high embryo toxicity could be found in the samples not only in the vicinity of the megacity São Paulo (Billings reservoir and Pinheiros River samples), but also downstream (in the reservoirs Barra Bonita, Promissão and Três Irmãos). Results confirm that most toxicity is due to the discharges of the metropolitan area of São Paulo. However, they also indicate additional sources of pollutants along the river course, probably from industrial, agricultural and agroindustrial residues, which contribute to the degradation of each area. The sediment contact fish embryo test showed to be powerful tool to detect embryo toxicity in sediments, not only by being a sensitive method, but also for taking into account bioavailability. This test provides an ecological highly realistic and relevant exposure scenario, and should therefore be added in ecotoxicological sediment quality assessments., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: BIBF 1120 is an oral, potent angiokinase inhibitor targeting receptors of the vascular endothelial growth factors, platelet-derived growth factors, and fibroblast growth factors. This phase I, accelerated titration study assessed the maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamic effects of BIBF 1120., Patients and Methods: Sixty-one patients with advanced cancers received BIBF 1120 in successive cohorts. Twenty-five received 50 to 450 mg once daily and 36 received 150 to 300 mg twice daily in 4-week treatment courses interspersed by 1 week of washout. Dynamic contrast-enhanced magnetic resonance imaging assessed antiangiogenic effect in 42 patients., Results: Most frequent BIBF 1120-related adverse events were mostly mild to moderate (Common Toxicity Criteria grade 1-2) nausea (68.9%), vomiting (45.9%), and diarrhea (44.3%). The majority of dose-limiting adverse events of Common Toxicity Criteria grade 3 or 4 were reversible liver enzyme elevations. The maximum tolerated dose was 250 mg of BIBF 1120 for once and twice daily dosing. BIBF 1120 was absorbed moderately fast (t(max) = 1-3 hours at steady state), with no deviation from dose linearity and no decrease of exposure over time. The gMean terminal half-life was from 13 to 19 hours. One complete and two partial responses occurred in patients with renal cell cancer (n = 2) and colorectal cancer (n = 1). Dynamic contrast-enhanced magnetic resonance imaging showed a significant reduction in tumor blood flow in 55% of evaluable patients., Conclusions: BIBF 1120 dosed continuously displayed a favorable safety and pharmacokinetics profile, and first efficacy signals were observed. Twice daily dosing permitted increased drug exposure without additional toxicity. Two hundred milligrams BIBF 1120 twice daily is the recommended dose for phase II monotherapy studies.

Time-resolved, contrast-enhanced 3D MR angiography combined with parallel imaging at 3T was applied to an intracranial arteriovenous malformation, a dural arteriovenous fistula, and an extracranial facial arteriovenous malformation. The temporal resolution was one image every 1.5 seconds. Arterial feeders were depicted in all three cases. Early venous drainage was observed in the intracerebral arteriovenous malformation and the dural arteriovenous fistula, but not in the facial arteriovenous malformation. All findings were concordant with conventional angiography.

We report a hemodynamical assessment of the blood turnover pattern as well as the imaging of cavernous hemangioma in a cavernous sinus using time-resolved contrast enhanced 2D projection MRA, also known as MR-DSA, and conventional digital subtraction angiography (DSA), before and after radiotherapy. MR-DSA showed very fast dynamical images of a contrast turnover pattern and was well matched with the findings obtained from DSA. MR-DSA is a non-invasive study, and can replace DSA in examining a vascular tumor for the initial work-up and follow-up examination.

We report the hemodynamic assessment in a patient with cerebral arteriovenous malformation using time-resolved magnetic resonance angiography (TRMRA), a non-invasive modality, and catheter-based digital subtraction angiography (DSA), before and after embolization. Comparison of the results showed that TR-MRA produced very fast dynamic images and the findings closely matched those obtained at DSA. For initial work-up and follow-up studies in patients with vascular lesions, TR-MRA and DSA are therefore comparable.

Cholinergic neurons of the mesopontine nuclei are strongly implicated in behavioral state regulation. One population of neurons in the cholinergic zone of the laterodorsal tegmentum and the pedunculopontine nuclei, referred to as rapid eye movement (REM)-on neurons, shows preferential discharge activity during REM sleep, and extensive data indicate a key role in production of this state. Another neuronal group present in the same cholinergic zone of the laterodorsal tegmentum and the pedunculopontine nuclei, referred to as Wake/REM-on neurons, shows preferential discharge activity during both wakefulness and REM sleep and is implicated in the production of electroencephalographic activation in both of these states. To test the hypothesis of differential serotonergic inhibition as an explanation of the different state-related discharge activity, we developed a novel methodology that enabled, in freely behaving animals, simultaneous unit recording and local perfusion of neuropharmacological agents using a microdialysis probe adjacent to the recording electrodes. Discharge activity of REM-on neurons was almost completely suppressed by local microdialysis perfusion of the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), although this agonist had minimal or no effect on the Wake/REM-on neurons. We conclude that selective serotonergic inhibition is a basis of differential state regulation in the mesopontine cholinergic nuclei, and that the novel methodology combining neurophysiological and neuropharmacological information from the freely behaving animal shows great promise for further insight into the neural basis of behavioral control.

Both subjective and electroencephalographic arousal diminish as a function of the duration of prior wakefulness. Data reported here suggest that the major criteria for a neural sleep factor mediating the somnogenic effects of prolonged wakefulness are satisfied by adenosine, a neuromodulator whose extracellular concentration increases with brain metabolism and which, in vitro, inhibits basal forebrain cholinergic neurons. In vivo microdialysis measurements in freely behaving cats showed that adenosine extracellular concentrations in the basal forebrain cholinergic region increased during spontaneous wakefulness as contrasted with slow wave sleep; exhibited progressive increases during sustained, prolonged wakefulness; and declined slowly during recovery sleep. Furthermore, the sleep-wakefulness profile occurring after prolonged wakefulness was mimicked by increased extracellular adenosine induced by microdialysis perfusion of an adenosine transport inhibitor in the cholinergic basal forebrain but not by perfusion in a control noncholinergic region.