skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Multiparametric Brain Hemodynamics Imaging Using a Combined Ultrafast Ultrasound and Photoacoustic System
Abstract Studying brain‐wide hemodynamic responses to different stimuli at high spatiotemporal resolutions can help gain new insights into the mechanisms of neuro‐ diseases and ‐disorders. Nonetheless, this task is challenging, primarily due to the complexity of neurovascular coupling, which encompasses interdependent hemodynamic parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral oxygen saturation (SO2). The current brain imaging technologies exhibit inherent limitations in resolution, sensitivity, and imaging depth, restricting their capacity to comprehensively capture the intricacies of cerebral functions. To address this, a multimodal functional ultrasound and photoacoustic (fUSPA) imaging platform is reported, which integrates ultrafast ultrasound and multispectral photoacoustic imaging methods in a compact head‐mountable device, to quantitatively map individual dynamics of CBV, CBF, and SO2as well as contrast agent enhanced brain imaging at high spatiotemporal resolutions. Following systematic characterization, the fUSPA system is applied to study brain‐wide cerebrovascular reactivity (CVR) at single‐vessel resolution via relative changes in CBV, CBF, and SO2in response to hypercapnia stimulation. These results show that cortical veins and arteries exhibit differences in CVR in the stimulated state and consistent anti‐correlation in CBV oscillations during the resting state, demonstrating the multiparametric fUSPA system's unique capabilities in investigating complex mechanisms of brain functions.  more » « less
Award ID(s):
2238878
PAR ID:
10515387
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Science
Volume:
11
Issue:
31
ISSN:
2198-3844
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Acoustically detecting the optical absorption contrast, photoacoustic imaging (PAI) is a highly versatile imaging modality that can provide anatomical, functional, molecular, and metabolic information of biological tissues. PAI is highly scalable and can probe the same biological process at various length scales ranging from single cells (microscopic) to the whole organ (macroscopic). Using hemoglobin as the endogenous contrast, PAI is capable of label-free imaging of blood vessels in the brain and mapping hemodynamic functions such as blood oxygenation and blood flow. These imaging merits make PAI a great tool for studying ischemic stroke, particularly for probing into hemodynamic changes and impaired cerebral blood perfusion as a consequence of stroke. In this narrative review, we aim to summarize the scientific progresses in the past decade by using PAI to monitor cerebral blood vessel impairment and restoration after ischemic stroke, mostly in the preclinical setting. We also outline and discuss the major technological barriers and challenges that need to be overcome so that PAI can play a more significant role in preclinical stroke research, and more importantly, accelerate its translation to be a useful clinical diagnosis and management tool for human strokes. 
    more » « less
  2. Multi-parametric photoacoustic microscopy (PAM) has emerged as a promising new technique for high-resolution quantification of hemodynamics and oxygen metabolism in the mouse brain. In this work, we have extended the scope of multi-parametric PAM to longitudinal, cortex-wide, awake-brain imaging with the use of a long-lifetime (24 weeks), wide-field (5 × 7 mm 2 ), light-weight (2 g), dual-transparency ( i.e., light and ultrasound) cranial window. Cerebrovascular responses to the window installation were examined in vivo, showing a complete recovery in 18 days. In the 22-week monitoring after the recovery, no dura thickening, skull regrowth, or changes in cerebrovascular structure and function were observed. The promise of this technique was demonstrated by monitoring vascular and metabolic responses of the awake mouse brain to ischemic stroke throughout the acute, subacute, and chronic stages. Side-by-side comparison of the responses in the ipsilateral (injury) and contralateral (control) cortices shows that despite an early recovery of cerebral blood flow and an increase in microvessel density, a long-lasting deficit in cerebral oxygen metabolism was observed throughout the chronic stage in the injured cortex, part of which proceeded to infarction. This longitudinal, functional-metabolic imaging technique opens new opportunities to study the chronic progression and therapeutic responses of neurovascular diseases. 
    more » « less
  3. Autoregulation and neurovascular coupling are key mechanisms that modulate myogenic tone (MT) in vessels to regulate cerebral blood flow (CBF) during resting state and periods of increased neural activity, respectively. To determine relative contributions of distinct vascular zones across different cortical depths in CBF regulation, we developed a simplified yet detailed and computationally efficient model of the mouse cerebrovasculature. The model integrates multiple simplifications and generalizations regarding vascular morphology, the hierarchical organization of mural cells, and potentiation/inhibition of MT in vessels. Our analysis showed that autoregulation is the result of the synergy between these factors, but achieving an optimal balance across all cortical depths and throughout the autoregulation range is a complex task. This complexity explains the non-uniformity observed experimentally in capillary blood flow at different cortical depths. In silico simulations of cerebral autoregulation support the idea that the cerebral vasculature does not maintain a plateau of blood flow throughout the autoregulatory range and consists of both flat and sloped phases. We learned that small-diameter vessels with large contractility, such as penetrating arterioles and precapillary arterioles, have major control over intravascular pressure at the entry points of capillaries and play a significant role in CBF regulation. However, temporal alterations in capillary diameter contribute moderately to cerebral autoregulation and minimally to functional hyperemia. In addition, hemodynamic analysis shows that while hemodynamics within capillaries remain relatively stable across all cortical depths throughout the entire autoregulation range, significant variability in hemodynamics can be observed within the first few branch orders of precapillary arterioles or transitional zone vessels. The computationally efficient cerebrovasculature model, proposed in this study, provides a novel framework for analyzing dynamics of the CBF regulation where hemodynamic and vasodynamic interactions are the foundation on which more sophisticated models can be developed. 
    more » « less
  4. Introduction Multi-series CT (MSCT) scans, including non-contrast CT (NCCT), CT Perfusion (CTP), and CT Angiography (CTA), are widely used in acute stroke imaging. While each scan has its advantage in disease diagnosis, the varying image resolution of different series hinders the ability of the radiologist to discern subtle suspicious findings. Besides, higher image quality requires high radiation doses, leading to increases in health risks such as cataract formation and cancer induction. Thus, it is highly crucial to develop an approach to improve MSCT resolution and to lower radiation exposure. Hypothesis MSCT imaging of the same patient is highly correlated in structural features, the transferring and integration of the shared and complementary information from different series are beneficial for achieving high image quality. Methods We propose TL-GAN, a learning-based method by using Transfer Learning (TL) and Generative Adversarial Network (GAN) to reconstruct high-quality diagnostic images. Our TL-GAN method is evaluated on 4,382 images collected from nine patients’ MSCT scans, including 415 NCCT slices, 3,696 CTP slices, and 271 CTA slices. We randomly split the nine patients into a training set (4 patients), a validation set (2 patients), and a testing set (3 patients). In preprocessing, we remove the background and skull and visualize in brain window. The low-resolution images (1/4 of the original spatial size) are simulated by bicubic down-sampling. For training without TL, we train different series individually, and for with TL, we follow the scanning sequence (NCCT, CTP, and CTA) by finetuning. Results The performance of TL-GAN is evaluated by the peak-signal-to-noise ratio (PSNR) and structural similarity (SSIM) index on 184 NCCT, 882 CTP, and 107 CTA test images. Figure 1 provides both visual (a-c) and quantity (d-f) comparisons. Through TL-GAN, there is a significant improvement with TL than without TL (training from scratch) for NCCT, CTP, and CTA images, respectively. These significances of performance improvement are evaluated by one-tailed paired t-tests (p < 0.05). We enlarge the regions of interest for detail visual comparisons. Further, we evaluate the CTP performance by calculating the perfusion maps, including cerebral blood flow (CBF) and cerebral blood volume (CBV). The visual comparison of the perfusion maps in Figure 2 demonstrate that TL-GAN is beneficial for achieving high diagnostic image quality, which are comparable to the ground truth images for both CBF and CBV maps. Conclusion Utilizing TL-GAN can effectively improve the image resolution for MSCT, provides radiologists more image details for suspicious findings, which is a practical solution for MSCT image quality enhancement. 
    more » « less
  5. Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the entire brain. Because of the potential significance of blood flow and oxygen supply simulations for illuminating spatiotemporal regulation inside the cortical microanatomy, there is a need to create mathematical models of the entire cerebral circulation with realistic anatomical detail. Our hypothesis is that an anatomically accurate reconstruction of the cerebrocirculatory architecture will inform about possible regulatory mechanisms of the neurovascular interface. In this article, we introduce large-scale networks of the murine cerebral circulation spanning the Circle of Willis, main cerebral arteries connected to the pial network down to the microcirculation in the capillary bed. Several multiscale models were generated from state-of-the-art neuroimaging data. Using a vascular network construction algorithm, the entire circulation of the middle cerebral artery was synthesized. Blood flow simulations indicate a consistent trend of higher hematocrit in deeper cortical layers, while surface layers with shorter vascular path lengths seem to carry comparatively lower red blood cell (RBC) concentrations. Moreover, the variability of RBC flux decreases with cortical depth. These results support the notion that plasma skimming serves a self-regulating function for maintaining uniform oxygen perfusion to neurons irrespective of their location in the blood supply hierarchy. Our computations also demonstrate the practicality of simulating blood flow for large portions of the mouse brain with existing computer resources. The efficient simulation of blood flow throughout the entire middle cerebral artery (MCA) territory is a promising milestone towards the final aim of predicting blood flow patterns for the entire brain. 
    more » « less