In Vivo Imaging of Cerebral Energy Metabolism with Two-Photon Fluorescence Lifetime Microscopy of NADH

Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism

Transient hypercapnia reveals an underlying cerebrovascular pathology in a murine model for HIV-1 associated neuroinflammation: role of NO-cGMP signaling and normalization by inhibition of cyclic nucleotide phosphodiesterase-5

Cerebral blood flow (CBF) is known to be dysregulated in persons with human immunodeficiency virus 1 (HIV-1), for uncertain reasons. This is an important issue because impaired vasoreactivity has been associated with increased risk of ischemic stroke, elevated overall cardiovascular risk and cognitive impairment

Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions

Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO2 range with a p50 of 3.4±0.6 mm Hg, thereby establishing a nearly binary reporter of significant, metabolically limiting hypoxia. The transient cortical tissue boundaries of NADH fluorescence exhibit remarkably delineated geometrical patterns, which define the limits of tissue oxygen diffusion from the cortical microcirculation and bear a striking resemblance to the ideal Krogh tissue cylinder. The visualization of microvessels and their regional contribution to oxygen delivery establishes penetrating arterioles as major oxygen sources in addition to the capillary network and confirms the existence of cortical oxygen fields with steep microregional oxygen gradients. Thus, two-photon NADH imaging can be applied to expose vascular supply regions and to localize functionally relevant microregional cortical hypoxia with micrometer spatial resolution

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts

Automated and assisted identification of stroke using feature-based brain imaging

Provided herein are systems and methods for automated identification of volumes of interest in volumetric brain images using artificial intelligence (AI) enhanced imaging to diagnose and treat acute stroke. The methods can include receiving image data of a brain having header data and voxel values that represent an interruption in blood supply of the brain when imaged, extracting the header data from the image data, populating an array of cells with the voxel values, applying a segmenting analysis to the array to generate a segmented array, applying a morphological neighborhood analysis to the segmented array to generate a features relationship array, where the features relationship array includes features of interest in the brain indicative of stroke, identifying three-dimensional (3D) connected volumes of interest in the features relationship array, and generating output, for display at a user device, indicating the identified 3D volumes of interest

Automated and assisted identification of stroke using feature-based brain imaging

Provided herein are systems and methods for automated identification of volumes of interest in volumetric brain images using artificial intelligence (AI) enhanced imaging to diagnose and treat acute stroke. The methods can include receiving image data of a brain having header data and voxel values that represent an interruption in blood supply of the brain when imaged, extracting the header data from the image data, populating an array of cells with the voxel values, applying a segmenting analysis to the array to generate a segmented array, applying a morphological neighborhood analysis to the segmented array to generate a features relationship array, where the features relationship array includes features of interest in the brain indicative of stroke, identifying three-dimensional (3D) connected volumes of interest in the features relationship array, and generating output, for display at a user device, indicating the identified 3D volumes of interest

Apparent Reversal of Early Ischemic Changes on Non‐Contrast Computed Tomography Following Successful Endovascular Reperfusion

Early ischemic changes seen on non‐contrast computed tomography secondary to cerebral edema is believed to indicate irreversible cellular injury. Computed tomography perfusion may overpredict the infarct core in patients with large vessel occlusion presenting in acute phase as these changes are potentially reversible if successful endovascular reperfusion is performed in a timely manner. This has led to the concept of “ghost infarct core” which is the mismatch in the infarct core as seen on follow‐up imaging. We present a case which potentially supports the concept of “ghost infarct core” evaluated not only by computed tomography perfusion but also non‐contrast computed tomography in a patient with large vessel occlusion following successful thrombectomy