Interobserver Agreement of visual and semi-quantitative methods in 99mTc-Methoxy-Isobuty-Isonitrile (MIBI) imaging for risk stratification of hypofunctional thyroid nodules.

AIM: 99mTc-Methoxy-Isobuty-Isonitrile (MIBI) imaging is used for risk stratifications of hypofunctioning thyroid nodules (TNs). MIBI uptake in the nodular tissue is compared to the uptake in the paranodular thyroid tissue. MIBI imaging may be interpreted visually and/or semi-quantitatively. This study aimed to evaluate the interobserver agreement (IOA) of different methods of interpreting MIBI imaging (visual and semi-quantitative approaches). METHODS: MIBI imaging data from 2018 to 2020 were collected. Four readers with varying work experience prospectively evaluated MIBI images (planar, SPECT/CT) visually and semi-quantitatively (Wash-Out Index (WOI)). After identifying the nodules on 99mTc-pertechnetate scintigram, the readers evaluated MIBI imaging data by using early, late, early-to-late, and SPECT late acquisitions. Region of interests (ROIs) were defined for semi-quantitative analysis and average counts were calculated using the WOI formula (by Campenni et al.) 1 2. IOA was assessed using Fleiss Kappa, Pearson correlation and Analysis of Variance (ANOVA). RESULTS: 23 patients with hypofunctioning nodules were included. Kappa analysis revealed an IOA of 0.57 for all readers for early imaging (moderate agreement); perfect matches were found in 57%. For late imaging, the IOA was 0.48 (moderate) for all, with perfect matches in 48%. The visual pattern (early-to-late) exhibited an IOA of 0.45 for all, with perfect matches in 57%. SPECT/CT evaluation showed an overall IOA of 0.44, with perfect matches in 48%. The semi-quantitative approach WOI yielded an overall result of 0.64 (good agreement) and perfect matches in 91%. CONCLUSION: The IOA for WOI was higher than for visual methods. The WOI is independent of the reader's experience level. Visual analysis requires a certain level of experience from the reader.

Amyloid-precursor-protein-lowering small molecules for disease modifying therapy of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia in the elderly with progressive cognitive decline and memory loss. According to the amyloid-hypothesis, AD is caused by generation and subsequent cerebral deposition of ß-amyloid (Aß). Aß is generated through sequential cleavage of the transmembrane Amyloid-Precursor-Protein (APP) by two endoproteinases termed beta- and gamma-secretase. Increased APP-expression caused by APP gene dosage effects is a risk factor for the development of AD. Here we carried out a large scale screen for novel compounds aimed at decreasing APP-expression. For this we developed a screening system employing a cell culture model of AD. A total of 10,000 substances selected for their ability of drug-likeness and chemical diversity were tested for their potential to decrease APP-expression resulting in reduced Aß-levels. Positive compounds were further evaluated for their effect at lower concentrations, absence of cytotoxicity and specificity. The six most promising compounds were characterized and structure function relationships were established. The novel compounds presented here provide valuable information for the development of causal therapies for AD.