ABSTRACT
Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.
ABSTRACT
Purpose: Clinical myocardial perfusion SPECT is commonly performed using static imaging. Dynamic SPECT enables extraction of quantitative as well as relative perfusion information. We aimed to evaluate the ability of dynamic SPECT for regular perfusion assessment in comparison to conventional SPECT in the context of thallium-201. Methods: Simulations were performed utilizing a 4D-NCAT phantom for a dual-head gamma camera via the SIMIND Monte-Carlo simulator. 64s acquisition time-frames were used to track these dynamic changes. Different summations of time-frames were performed to create each dataset, which were compared to a standard static dataset. In addition, the effect of different delay-times post-injection was assessed. Twenty-segment analysis of perfusion was performed via the QPS analyser. Dynamic data were subsequently acquired in clinical studiesusing simulation-optimized protocols. Results: For different summations of time-frames, perfusion scores in the basal and mid regions revealed 14.4% and 7.3% increases in dynamic SPECT compared to conventional imaging, with maximum changes in the basal anterior, while the distal and apical segments did not show noticeable changes. Specifically, dynamic imaging including 4 to 6 time-frames yielded enhanced correlation [R=0.957] with conventional imaging, in comparision to the usage of less time frames. Greatest correlation with conventional imaging was obtained for post-injection delays of 320 to 448s [R=0.982 to R=0.988]. Conclusion: While dynamic SPECT opens up an important opportunity for quantitative assessment [e.g. via generation of kinetic parameters], it was shown to generate highly consistent perfusion information compared to established conventional imaging. Future work focuses on merging these two important capabilities