The white matter is the structure of the brain that declines most with age-almost 30%, but little is known about the age-effect on the fibers that constitute the white matter. In the present study, the total length of myelinated fibers was measured with a newly developed stereologic method. Specimens came from 36 normal Danes (18 males and 18 females) with an age ranging between 18 and 93 years. Samples were taken systematically and randomly from the white matter, and the biopsy specimens were randomly rotated before sectioning to avoid bias due to the anisotropic nature of nerve fibers. The fibers were counted at light microscopic level at approximately 10,000x magnification, and the diameter of each counted fiber was measured to get the diameter distribution. Males were found to have a total myelinated fiber length of 176,000 km at the age of 20 and 97,200 km at the age of 80, whereas the total length in females was 149,000 km at the age of 20 and 82,000 km at the age of 80. This finding corresponds to a 10% decrease per decade or a total decrease of 45% from the age of 20 to 80 years, and a sex difference of 16%. The fiber diameter distribution showed that primarily the thinner fibers were lost with a relative preservation of the thicker ones. The marked loss of myelinated nerve fibers with age could explain some of the cognitive decline seen in the elderly.

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The serotonin 4 receptor (5-HT 4 receptor) is known to be involved in learning and memory. We evaluated for the first time the quantification of a novel 5-HT 4 receptor radioligand, 11 C-SB207145, for in vivo brain imaging with PET in humans. Methods: For evaluation of reproducibility, 6 subjects were scanned twice with 11 C-SB207145 on the same day. A further 2 subjects were scanned before and after blocking with the selective 5-HT 4 receptor inverse agonist piboserod (SB207266). Arterial blood samples were drawn for the calculation of metabolite-corrected arterial input functions. Regions of interest were delineated automatically on the individual's MR images coregistered to the PET images, and regional time-activity curves were extracted. Quantitative tracer kinetic modeling was investigated with 1-and 2-tissue-compartment models using plasma input functions and the simplified reference tissue model (SRTM). Results: 11 C-SB207145 readily entered the brain and showed a distribution consistent with the known localization of the 5-HT 4 receptor. Using plasma input models, the time-activity data were well described by the 2-tissue-compartment model in all regions and allowed for the estimate of binding potentials relative to the reference region (BP ND : striatum, 3.38 6 0.72; hippocampus, 0.82 6 0.19; parietal cortex, 0.30 6 0.08). Quantification with the 1-tissue-compartment model, 2-tissue-compartment model, and SRTM were associated with good test-retest reproducibility and time stability. However, the SRTM-generated BP ND values in the striatum were underestimated by 20%243% in comparison to the 2-tissue-compartment model. The blocking study with piboserod confirmed that the radioligand was selective for the 5-HT 4 receptor, that the cerebellum was a suitable reference region devoid of specific binding, and that nonspecific binding was constant across brain regions. Conclusion: In vivo imaging of cerebral 5-HT 4 receptors can be determined reliably using 11 C-207145 PET with arterial input in humans. SRTM showed high reproducibility and reliability but bias in the striatum, and therefore, the use of SRTM should be considered carefully for individual applications.

Aim: Positron emission tomography (PET) imaging is a useful tool for assisting in correct differentiation of tumor progression from reactive changes. O-(2-18F-fluoroethyl)-L-tyrosine (FET)-PET in combination with MRI can add valuable information for clinical decision making. Acquiring FET-PET/MRI simultaneously allows for a one-stop-shop that limits the need for a second sedation or anesthesia as with PET and MRI in sequence. PET/MRI is challenged by lack of a direct measure of photon attenuation. Accepted solutions for attenuation correction (AC) might not be applicable to pediatrics. The aim of this study was to evaluate the use of the subject-specific MR-derived AC method RESOLUTE, modified to a pediatric cohort, against the performance of an MR-AC technique based on deep learning in a pediatric brain tumor cohort.Methods: The modifications to RESOLUTE and the implementation of a deep learning method were performed using 79 pediatric patient examinations. We analyzed the 36 of these with active brain tumor area above 1 mL. We measured background (B), tumor mean and maximal activity (TMEAN, TMAX), biological tumor volume (BTV), and calculated the clinical metrics TMEAN/B and TMAX/B.Results: Overall, we found both RESOLUTE and our DeepUTE methodologies to accurately reproduce the CT-AC clinical metrics. Regardless of age, both methods were able to obtain AC maps similar to the CT-AC, albeit with DeepUTE producing the most similar based on both quantitative metrics and visual inspection. In the patient-by-patient analysis DeepUTE was the only technique with all patients inside the predefined acceptable clinical limits. It also had a higher precision with relative %-difference to the reference CT-AC (TMAX/B mean: -0.1%, CI: [-0.8%, 0.5%], p = 0.54) compared to RESOLUTE (TMAX/B mean: 0.3%, CI: [-0.6%, 1.2%], p = 0.67) and DIXON-AC (TMAX/B mean: 5.9%, CI: [4.5%, 7.4%], p < 0.0001).Conclusion: Overall, we found DeepUTE to be the AC method that most robustly reproduced the CT-AC clinical metrics per se, closely followed by RESOLUTE modified to pediatric cohorts. The added accuracy due to better noise handling of DeepUTE, ease of use, as well as the improved runtime makes DeepUTE the method of choice for PET/MRI attenuation correction.