Cerebral blood flow recorded at high sensitivity in two dimensions using high resolution optical imaging

Knowledge about sensory-evoked blood-flow changes is essential for constraining hemodynamic response models used to interpret functional brain imaging signals, such as fMRI. Here, we extracted 2-dimensional blood-flow and its temporal modulations from high-resolution optical imaging data in the awake monkey. Optical imaging allows to track moving erythrocytes (or small clusters thereof), thus providing, albeit noisy, information about their velocity in individual blood vessels, across the whole imaged area. Here, we illustrate the algorithms that allowed us to extract, at the single micro-vessel level, red blood cell (RBC) motion information from the noisy optical signals. For this purpose, we developed an algorithm that is both robust and computationally efficient, using the structure tensor, known to detect an average direction of image intensity gradient. This structure tensor tool is applied to detect trajectory directions in the spatio-temporal data. Since blood-flow modulation by the cardiac pulsation was clearly detected, our method should be applicable also to study blood-flow modulations by neuronal activity, and their spatio-temporal patterns

The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined

Fine-Scale Spatial Organization of Face and Object Selectivity in the Temporal Lobe: Do Functional Magnetic Resonance Imaging, Optical Imaging, and Electrophysiology Agree?

The spatial organization of the brain's object and face representations in the temporal lobe is critical for understanding high-level vision and cognition but is poorly understood. Recently, exciting progress has been made using advanced imaging and physiology methods in humans and nonhuman primates, and the combination of such methods may be particularly powerful. Studies applying these methods help us to understand how neuronal activity, optical imaging, and functional magnetic resonance imaging signals are related within the temporal lobe, and to uncover the fine-grained and large-scale spatial organization of object and face representations in the primate brain

In Vivo Vascular Imaging with Photoacoustic Microscopy

Photoacoustic (PA) tomography (PAT) has received extensive attention in the last decade for its capability to provide label-free structural and functional imaging in biological tissue with highly scalable spatial resolution and penetration depth. Compared to modern optical modalities, PAT offers speckle-free images and is more sensitive to optical absorption contrast (with 100% relative sensitivity). By implementing different regimes of optical wavelength, PAT can be used to image diverse light-absorbing biomolecules. For example, hemoglobin is of particular interest in the visible wavelength regime owing to its dominant absorption, and lipids and water are more commonly studied in the near-infrared regime. In this dissertation, one challenge was to quantitatively investigate red-blood-cell dynamics in nailfold capillaries with single-cell resolution PA microscopy (PAM). We recruited healthy volunteers and measured multiple hemodynamic parameters based on individual red blood cells (RBCs). Statistical analysis revealed the process of oxygen release and changes in flow speed for RBCs in a capillary. For the first time on record, oxygen release from individual RBCs in human capillaries was imaged with nearly real-time speed, and the work paved the way for our following study of a specific blood disorder. We next conducted a pilot study on sickle cell disease (SCD), measuring and comparing the parameters related to RBC dynamics between healthy subjects and patients with SCD. In the patient group, we found that capillaries tended to be more tortuous, dilated, and had higher number density. In addition, abnormal RBCs tended to have lower oxygenation in the inlet of a capillary, from where they flowed slower and released a larger fraction of oxygen than normal RBCs. As the only imaging modality able to observe the real-time dynamics of the oxygen release of individual RBCs, PAM provides medically valuable information for diagnostic purposes. As the last focus of this dissertation, we tackled the limited view problem in PAM by introducing an off-axis illumination technique for complementing the original detection view. We demonstrated this technique numerically and then experimentally on phantoms and animals. This simple but very effective method revealed abundant vertical vasculature in a mouse brain that had long been missed by conventional top-illumination PAM. This technique greatly advances future studies on neurovascular responses in mouse brains

Deep convolutional neural networks for segmenting 3D in vivo multiphoton images of vasculature in Alzheimer disease mouse models

The health and function of tissue rely on its vasculature network to provide reliable blood perfusion. Volumetric imaging approaches, such as multiphoton microscopy, are able to generate detailed 3D images of blood vessels that could contribute to our understanding of the role of vascular structure in normal physiology and in disease mechanisms. The segmentation of vessels, a core image analysis problem, is a bottleneck that has prevented the systematic comparison of 3D vascular architecture across experimental populations. We explored the use of convolutional neural networks to segment 3D vessels within volumetric in vivo images acquired by multiphoton microscopy. We evaluated different network architectures and machine learning techniques in the context of this segmentation problem. We show that our optimized convolutional neural network architecture, which we call DeepVess, yielded a segmentation accuracy that was better than both the current state-of-the-art and a trained human annotator, while also being orders of magnitude faster. To explore the effects of aging and Alzheimer's disease on capillaries, we applied DeepVess to 3D images of cortical blood vessels in young and old mouse models of Alzheimer's disease and wild type littermates. We found little difference in the distribution of capillary diameter or tortuosity between these groups, but did note a decrease in the number of longer capillary segments ($>75\mu m$) in aged animals as compared to young, in both wild type and Alzheimer's disease mouse models.Comment: 34 pages, 9 figure

Systematic investigation of changes in oxidized cerebral cytochrome c oxidase concentration during frontal lobe activation in healthy adults

Using transcranial near-infrared spectroscopy (NIRS) to measure changes in the redox state of cerebral cytochrome c oxidase (Δ[oxCCO]) during functional activation in healthy adults is hampered by instrumentation and algorithm issues. This study reports the Δ[oxCCO] response measured in such a setting and investigates possible confounders of this measurement. Continuous frontal lobe NIRS measurements were collected from 11 healthy volunteers during a 6-minute anagram-solving task, using a hybrid optical spectrometer (pHOS) that combines multi-distance frequency and broadband components. Only data sets showing a hemodynamic response consistent with functional activation were interrogated for a Δ[oxCCO] response. Simultaneous systemic monitoring data were also available. Possible influences on the Δ[oxCCO] response were systematically investigated and there was no effect of: 1) wavelength range chosen for fitting the measured attenuation spectra; 2) constant or measured, with the pHOS in real-time, differential pathlength factor; 3) systemic hemodynamic changes during functional activation; 4) changes in optical scattering during functional activation. The Δ[oxCCO] response measured in the presence of functional activation was heterogeneous, with the majority of subjects showing significant increase in oxidation, but others having a decrease. We conclude that the heterogeneity in the Δ[oxCCO] response is physiological and not induced by confounding factors in the measurements. © 2012 Optical Society of America

Use of functional near-infrared spectroscopy to evaluate cognitive change when using healthcare simulation tools

This is an accepted manuscript of an article published by BMJ on 01/11/2020, available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936993/ The accepted version of the publication may differ from the final published version.Background The use of brain imaging techniques in healthcare simulation is relatively rare. However, the use of mobile, wireless technique, such as functional nearinfrared spectroscopy (fNIRS), is becoming a useful tool for assessing the unique demands of simulation learning. For this study, this imaging technique was used to evaluate cognitive load during simulation learning events. Methods This study took place in relation to six simulation activities, paired for similarity, and evaluated comparative cognitive change between the three task pairs. The three paired tasks were: receiving a (1) face-toface and (2) video patient handover; observing a simulated scene in (1) two dimensions and (2) 360° field of vision; and on a simulated patient (1) taking a pulse and (2) taking a pulse and respiratory rate simultaneously. The total number of participants was n=12. Results In this study, fNIRS was sensitive to variations in task difficulty in common simulation tools and scenarios, showing an increase in oxygenated haemoglobin concentration and a decrease in deoxygenated haemoglobin concentration, as tasks increased in cognitive load. Conclusion Overall, findings confirmed the usefulness of neurohaemoglobin concentration markers as an evaluation tool of cognitive change in healthcare simulation. Study findings suggested that cognitive load increases in more complex cognitive tasks in simulation learning events. Task performance that increased in complexity therefore affected cognitive markers, with increase in mental effort required

High-speed extended-volume blood flow measurement using engineered point-spread function

Experimental characterization of blood flow in living organisms is crucial for understanding the development and function of cardiovascular systems, but there has been no technique reported for snapshot imaging of thick samples in large volumes with high precision. We have combined computational microscopy and the diffraction-free, self-bending property of Airy-beams to track fluorescent beads with sub-micron precision through an extended axial range (up to 600 \textmu m) within the flowing blood of 3 days post-fertilization (dpf) zebrafish embryos. The spatial trajectories of the tracer beads within flowing blood were recorded during transit through both cardinal and intersegmental vessels, and the trajectories were found to be consistent with the segmentation of the vasculature recorded using selective-plane illumination microscopy (SPIM). This method provides sufficiently precise spatial and temporal measurement of 3D blood flow that has the potential for directly probing key biomechanical quantities such as wall shear stress, as well as exploring the fluidic repercussions of cardiovascular diseases. Although we demonstrate the technique for blood flow, the ten-fold better enhancement in the depth range offers improvements in a wide range of applications of high-speed precision measurement of fluid flow, from microfluidics through measurement of cell dynamics to macroscopic aerosol characterizations