Cerebrovascular dysfunction plays a role not only in vascular causes of cognitive impairment but also in Alzheimer's disease (AD). We hypothesized that cerebral autoregulation is impaired in patients with AD compared to subjects with mild cognitive impairment (MCI) and controls. Dynamic cerebral autoregulation (dCA) was investigated in 17 AD patients, 19 MCI subjects, and 20 controls (C). Groups were matched for age, gender, and level of education. Electrocardiogram and non-invasive finger arterial blood pressure were measured and transcranial doppler ultrasonography was used to measure cerebral blood flow velocity in right and left middle cerebral artery (MCA). Cerebrovascular resistance index (CVRi) was also computed. dCA in supine position was quantified based on spontaneous blood pressure variations by computation of the linear transfer function between arterial blood pressure and MCA cerebral blood flow velocity. dCA gain and phase were evaluated for different frequency bands. Results were also evaluated using a 3-parameter windkessel model (WKM). CVRi was significantly higher in AD (2.9 ± 0.2) compared to both MCI (2.3 ± 0.1, p = 0.02) and C (2.1 ± 0.1 mmHgs/cm, p = 0.002). Five MCI patients who converted to AD during the course of the study also had higher CVRi compared to non-converters (2.8 ± 0.6 versus 2.1 ± 0.5 mmHgs/cm, p < 0.05). No significant differences in dCA gain and phase were found. In terms of the WKM approach, in the order C→MCI→AD groups showed about equal arterial resistance and peripheral compliance, but increased peripheral vasculature resistance (26 ± 2 versus 36 ± 3 mmHgs/ml in C resp. AD, p = 0.004). In conclusion, AD patients compared to MCI patients and controls have increased CVRi, whereas dCA parameters do not seem to differentiate AD patients. For MCI patients, CVRi might have predictive value in developing AD.

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Background Dosimetry after peptide receptor radionuclide therapy (PRRT) is increasing; however, comparing or pooling of dosimetric results can be challenging since different approaches are used. The aim of this study was to perform a head-to-head comparison of post-PRRT curve fitting and dosimetry obtained from two commercial software Hybrid Viewer Dosimetry and PLANET Dose. Methods Post-therapy imaging included planar scintigraphy at 0.5, 4, 24 and 72 h post-injection of [177Lu]Lu-DOTA-TATE for kinetics and SPECT/CT at 24 h for quantification. On planar imaging, 2 cm regions-of-interest were positioned within the inferior pole of the kidneys and kidney cortex was segmented on low-dose CT. On both planar and SPECT/CT, 2 cm spheres were positioned in the proximal humerus (red marrow equivalent) and in the region with the highest uptake in tumour lesions. TACs were estimated with mono- and bi-exponential fits in both software systems, after which tissue absorbed (kidney, red marrow, tumour) and biological effective doses (kidney) were calculated. Agreement-ICC, Spearman correlation and Bland-Altman plots were used to compare results. Results Mono-exponential fits showed the most comparable correlation between the measured and fitted data between both software. The ICC between absorbed dose outcomes was > 0.7 in tumour lesions and kidneys, but negative for the red marrow. Spearman correlation was > 0.9 for mono-exponential fits in kidneys and tumour lesions, and −0.7 in red marrow. Bi-exponential fits resulted in lower correlations and agreement values. Concordance between both software packages concerning the number of PRRT cycles with 7.4 GBq was observed based on a biological effective dose limit of 27 Gy to the kidneys. Conclusion [177Lu]Lu-DOTA-TATE dosimetry results of two software packages were comparable in the same dataset, despite the limited number of imaging time-points. However, these results should be verified in a larger cohort before pooling of clinical data, as the obtained results will depend on acquisition protocol, timing and lesions definition.

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