MR-Less Surface-Based Amyloid Assessment Based on 11C PiB PET

Background

β-amyloid (Aβ) plaques in brain''s grey matter (GM) are one of the pathological hallmarks of Alzheimer''s disease (AD), and can be imaged in vivo using Positron Emission Tomography (PET) with ¹¹C or ¹⁸F radiotracers. Estimating Aβ burden in cortical GM has been shown to improve diagnosis and monitoring of AD. However, lacking structural information in PET images requires such assessments to be performed with anatomical MRI scans, which may not be available at different clinical settings or being contraindicated for particular reasons. This study aimed to develop an MR-less Aβ imaging quantification method that requires only PET images for reliable Aβ burden estimations.

Materials and Methods

The proposed method has been developed using a multi-atlas based approach on ¹¹C-PiB scans from 143 subjects (75 PiB+ and 68 PiB- subjects) in AIBL study. A subset of 20 subjects (PET and MRI) were used as atlases: 1) MRI images were co-registered with tissue segmentation; 2) 3D surface at the GM-WM interfacing was extracted and registered to a canonical space; 3) Mean PiB retention within GM was estimated and mapped to the surface. For other participants, each atlas PET image (and surface) was registered to the subject''s PET image for PiB estimation within GM. The results are combined by subject-specific atlas selection and Bayesian fusion to generate estimated surface values.

Results

All PiB+ subjects (N = 75) were highly correlated between the MR-dependent and the PET-only methods with Intraclass Correlation (ICC) of 0.94, and an average relative difference error of 13% (or 0.23 SUVR) per surface vertex. All PiB- subjects (N = 68) revealed visually akin patterns with a relative difference error of 16% (or 0.19 SUVR) per surface vertex.

Conclusion

The demonstrated accuracy suggests that the proposed method could be an effective clinical inspection tool for Aβ imaging scans when MRI images are unavailable.     

Eleven ancestral gene families lost in mammals and vertebrates while otherwise universally conserved in animals

Background  

Gene losses played a role which may have been as important as gene and genome duplications and rearrangements, in modelling today species' genomes from a common ancestral set of genes. The set and diversity of protein-coding genes in a species has direct output at the functional level. While gene losses have been reported in all the major lineages of the metazoan tree of life, none have proposed a focus on specific losses in the vertebrates and mammals lineages. In contrast, genes lost in protostomes (i.e. arthropods and nematodes) but still present in vertebrates have been reported and extensively detailed. This probable over-anthropocentric way of comparing genomes does not consider as an important phenomena, gene losses in species that are usually described as "higher". However reporting universally conserved genes throughout evolution that have recently been lost in vertebrates and mammals could reveal interesting features about the evolution of our genome, particularly if these losses can be related to losses of capability.     

Insulin stimulates generation of intracellular mediators in rat heart

Insulin treatment of rats results in an increased amount or activity of insulin mediators in heart muscle. The mediators stimulated mitochondrial pyruvate dehydrogenase and inhibited glucagon-stimulated adenylate cyclase. The mediators were copurified by ultrafiltration, ethanol extraction, Dowex cation-exchange, and QAE-Sephadex anion-exchange chromatography. The activities of the two mediators were separated by Sephadex G-10 chromatography. Fasting rats for 72 h diminished the mediator response to insulin treatment. These results, taken together with previous reports, indicate that insulin generates a number of mediators which have a ubiquitous tissue distribution. The activity of these mediators, like insulin responsiveness, is altered by the metabolic state of the animal.     

The control and biological importance of intratumoural aromatase in breast cancer

The existence of aromatase activity in human breast carcinomas has been established for about 20 years but the clinical and biological importance of this remains unclear. A number of studies in clinical material suggest that aromatase activity may be a prerequisite of response to aromatase inhibitors and that aromatase activity may be enhanced in those tumours relapsing during treatment with one such inhibitor, aminoglutethimide. These results would carry more significance, however, if it was demonstrable that the growth of breast carcinomas is affected by the conversion of androgens to oestrogens by intratumoural aromatase. We have tried to address this by establishing model systems with aromatase-transfected MCF7 breast cancer cells. We have demonstrated that these cells can be stimulated mitogenically with androgen and that this proliferation is suppressible with aromatase inhibitors. Similarly the growth of aromatase transfected cells but not wild type cells as xenografts is supported by androstenedione and inhibitable by both the steroidal aromatase inhibitor, 4-hydroxyandrostenedione and the non-steroidal inhibitor, CGS 20267. Work with the former of these, which is a suicide inhibitor allowed us to demonstrate that growth can proceed with aromatase activity approximating to the highest level seen in breast carcinomas indicating that at least at this extreme level the intratumoural conversion of androgens to oestrogens may indeed be able to support tumour growth. Further work with this model system should allow us to define the minimal amount of intratumoural activity which can support tumour growth.     

Variability of Euphausia superba populations near Elephant Island and the South Shetlands: 1981 vs. 1984

Summary March 1981 and 1984 Euphausia superba populations were compared using acoustics and net catches near Elephant Island, the South Shetlands, and in the Bransfield Strait. In 1981, krill tended to form large, thick swarms and in 1984, smaller, more dispersed, shallower patches. March body lengths of juvenile-adult krill were 22–59 mm in 1981 and 13–59 mm in 1984. Near Elephant I. in 1981, krill >45 mm were most numerous; in 1984 sizes <45 mm were dominant. In March 1984, the larger (>45 mm) body-size group was prereproductive and occurred from just west of Elephant I. westward into waters north of the South Shetlands; in 1981 the larger krill were postreproductive and more widely distributed in the Elephant I. area. Overall, netted postlarval krill, 1981 vs. 1984, averaged 73 vs. 48 individuals/m², or 54 vs. 16 g/m²; acoustic biomass estimates were 229 vs. 134–201 g/m². Larvae near Elephant I. averaged >2000/m² in 1981 vs. <1/m² in 1984—compatible with respective March reproductive states. Net-type comparisons revealed short-term (15 min to 6h) variability of a similar scale in both MOCNESS and bongo net catches, but bongo abundances averaged greater. Variation in maturity composition across 1981 swarms, patches, and random transects was like variation among the random 1984 tows; spatial distributions were more heterogeneous in 1984. The March 1984 krill of 20–44 mm (Year-2, mode 34 mm) relate to November 1983 krill of 9–30 mm (mode 21 mm), indicating growth averaging 12 mm during the season. Body-lengths and size-frequency modes of Year-2 and combined Years-3,3+ krill from comparable Feb-Mar data collected since 1968 suggest trends between times when (1) Year-2 krill average small and peak reproduction seems to be late in the season and/or weak (1979, 1982–1984), and (2) Year-2 krill are larger, and reproduction is possibly earlier and more successful (1976, 1980, 1981).