Non-invasive Deep-Brain Imaging with 3D Integrated Photoacoustic Tomography and Ultrasound Localization Microscopy (3D-PAULM).

Photoacoustic computed tomography (PACT) is a proven technology for imaging hemodynamics in deep brain of small animal models. PACT is inherently compatible with ultrasound (US) imaging, providing complementary contrast mechanisms. While PACT can quantify the brain's oxygen saturation of hemoglobin (sO2), US imaging can probe the blood flow based on the Doppler effect. Further, by tracking gas-filled microbubbles, ultrasound localization microscopy (ULM) can map the blood flow velocity with sub-diffraction spatial resolution. In this work, we present a 3D deep-brain imaging system that seamlessly integrates PACT and ULM into a single device, 3D-PAULM. Using a low ultrasound frequency of 4 MHz, 3D-PAULM is capable of imaging the whole-brain hemodynamic functions with intact scalp and skull in a totally non-invasive manner. Using 3D-PAULM, we studied the mouse brain functions with ischemic stroke. Multi-spectral PACT, US B-mode imaging, microbubble-enhanced power Doppler (PD), and ULM were performed on the same mouse brain with intrinsic image co-registration. From the multi-modality measurements, we future quantified blood perfusion, sO2, vessel density, and flow velocity of the mouse brain, showing stroke-induced ischemia, hypoxia, and reduced blood flow. We expect that 3D-PAULM can find broad applications in studying deep brain functions on small animal models.

Docosahexaenoic acid attenuates adipose tissue angiogenesis and insulin resistance in high fat diet-fed middle-aged mice via a sirt1-dependent mechanism.

SCOPE: Docosahexaenoic acid (DHA; C22: 6, n-3), one of PUFAs, exerts beneficial effects on inflammatory diseases, obesity and diabetes. Angiogenesis in adipose tissue has a major role in the development of obesity and its related metabolic complications. Inhibition of angiogenesis is an emerging strategy for the novel treatment for obesity. Thus, we examined the effect of DHA on angiogenesis in adipose tissues and investigated the underlying mechanisms. METHODS AND RESULTS: In high-fat diet (HFD) fed middle-aged mice, DHA inhibited the macrophage-derived inflammation and angiogenesis in adipose tissues, reduced adipocyte size and body fat composition and improved insulin sensitivity. Moreover, DHA reversed the HFD-induced reduction of Sirt1 in adipose tissues. Interestingly, the effects of DHA were attenuated by lentivirus-mediated Sirt1 knockdown with increasing expression of markers of macrophage-derived inflammation and angiogenesis, associated with impaired insulin sensitivity. CONCLUSION: Overall, our findings demonstrated that DHA reduced angiogenesis of adipose tissues and attenuated insulin resistance in HFD-induced obese mice via the activation of Sirt1.