Cardiovascular Applications of Hyperpolarized MRI

Many applications of MRI are limited by an inherently low sensitivity. Previous attempts to overcome this insensitivity have focused on the use of MRI systems with stronger magnetic fields. However, the gains that can be achieved in this way are relatively small and increasing the magnetic field invariably leads to greater technical challenges. More recently, the development of a range of techniques, which can be gathered under the umbrella term of “hyperpolarization,” has offered potential solutions to the low sensitivity. Hyperpolarization techniques have been demonstrated to temporarily increase the signal available in an MRI experiment by as much as 100,000-fold. This article outlines the main hyperpolarization techniques that have been proposed and explains how they can increase MRI signals. With particular emphasis on the emerging technique of dynamic nuclear polarization, the existing preclinical cardiovascular applications are reviewed and the potential for clinical translation is discussed

Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk

Rapid incision of the Mekong River in the middle Miocene linked to monsoonal precipitation

The uplift of orogenic plateaus has been assumed to be coincident with the fluvial incision of the gorges that commonly cut plateau margins. The Mekong River, which drains the eastern Qiangtang Terrane and southeastern Tibetan Plateau, is one of the ten largest rivers in the world by water and sediment discharge. When the Mekong River was established remains highly debated—with estimates that range from more than 55 to less than 5 million years ago—despite being a key constraint on the elevation history of the Tibetan Plateau. Here we report low-temperature thermochronology data from river bedrock samples that reveal a phase of rapid downward incision (>700 m) of the Mekong River during the middle Miocene about 17 million years ago, long after the uplift of the central and southeastern Tibetan Plateau. However, this coincides with a period of enhanced East Asian summer monsoon precipitation over the region compared with the early Miocene. Using stream profile modelling, we demonstrate that such an increase in precipitation could have produced the observed incision in the Mekong River. In the absence of an obvious tectonic contribution, we suggest that the rapid incision of the Tibetan Plateau and the establishment of the Mekong River in the middle Miocene may be attributed to increased erosion during a period of high monsoon precipitation