Noninvasive high-speed photoacoustic tomography of cerebral hemodynamics in awake-moving rats.
Ontology highlight
ABSTRACT:
SUBMITTER: Tang J
PROVIDER: S-EPMC4527999 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Significance: Having a clear understanding of functional hyperemia is crucial for functional brain imaging and neurological disease research. Vasodilation induced by sensory stimulus propagates from the arterioles to the upstream pial arteries in a retrograde fashion. As retrograde vasodilation occurs briefly in the early stage of functional hyperemia, an imaging technique with a high temporal resolution is required for its measurement. Aim: We aimed to present an imaging method to measure stimulus-induced retrograde vasodilation in awake animals. Approach: An imaging method based on optical coherence tomography angiography, which enables a high-speed and label-free vessel diameter measurement, was developed and applied for the investigation. Results: The propagation speed of retrograde vasodilation of pial artery was measured in awake mice. Other characteristics of functional hyperemia such as temporal profile and amplitude of the vascular response were also investigated. Conclusions: Our results provide detailed information of stimulus-induced hemodynamic response in the brain of awake mice and suggest the potential utility of our imaging method for the study of functional hyperemia in normal and diseased brain.
| S-EPMC7481125 | biostudies-literature
Project description:Photoacoustic computed tomography (PACT) has generated increasing interest for uses in preclinical research and clinical translation. However, the imaging depth, speed, and quality of existing PACT systems have previously limited the potential applications of this technology. To overcome these issues, we developed a three-dimensional photoacoustic computed tomography (3D-PACT) system that features large imaging depth, scalable field of view with isotropic spatial resolution, high imaging speed, and superior image quality. 3D-PACT allows for multipurpose imaging to reveal detailed angiographic information in biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualize whole brain vasculatures and hemodynamics. In the human breast, an in vivo imaging depth of 4 cm is achieved by scanning the breast within a single breath hold of 10 s. Here, we introduce the 3D-PACT system to provide a unique tool for preclinical research and an appealing prototype for clinical translation.
| S-EPMC7873071 | biostudies-literature
Project description:Understanding the relationship between brain function and natural behavior remains a significant challenge in neuroscience because there are very few convincing imaging/recording tools available for the evaluation of awake and freely moving animals. Here, we employed a miniaturized head-mounted scanning photoacoustic imaging (hmPAI) system to image real-time cortical dynamics. A compact photoacoustic (PA) probe based on four in-house optical fiber pads and a single custom-made 48-MHz focused ultrasound transducer was designed to enable focused dark-field PA imaging, and miniature linear motors were included to enable two-dimensional (2D) scanning. The total dimensions and weight of the proposed hmPAI system are only approximately 50 × 64 × 48 mm and 58.7 g (excluding cables). Our ex vivo phantom experimental tests revealed that a spatial resolution of approximately 0.225 mm could be achieved at a depth of 9 mm. Our in vivo results further revealed that the diameters of cortical vessels draining into the superior sagittal sinus (SSS) could be clearly imaged and continuously observed in both anesthetized rats and awake, freely moving rats. Statistical analysis showed that the full width at half maximum (FWHM) of the PA A-line signals (relative to the blood vessel diameter) was significantly increased in the selected SSS-drained cortical vessels of awake rats (0.58 ± 0.17 mm) compared with those of anesthetized rats (0.31 ± 0.09 mm) (p < 0.01, paired t-test). In addition, the number of pixels in PA B-scan images (relative to the cerebral blood volume (CBV)) was also significantly increased in the selected SSS-drained blood vessels of awake rats (107.66 ± 23.02 pixels) compared with those of anesthetized rats (81.99 ± 21.52 pixels) (p < 0.01, paired t-test). This outcome may result from a more active brain in awake rats than in anesthetized rats, which caused cerebral blood vessels to transport more blood to meet the increased nutrient demand of the tissue, resulting in an obvious increase in blood vessel volume. This hmPAI system was further validated for utility in the brains of awake and freely moving rats, showing that their natural behavior was unimpaired during vascular imaging, thereby providing novel opportunities for studies of behavior, cognition, and preclinical models of brain diseases.
| S-EPMC8615926 | biostudies-literature
Project description:Conventional methods for breast tumor margins assessment need a long turnaround time, which may lead to re-operation for patients undergoing lumpectomy surgeries. Photoacoustic tomography (PAT) has been shown to visualize adipose tissue in small animals and human breast. Here, we demonstrate a customized multimodal ultrasound and PAT system for intraoperative breast tumor margins assessment using fresh lumpectomy specimens from 66 patients. The system provides the margin status of the entire excised tissue within 10 minutes. By subjective reading of three researchers, the results show 85.7% [95% confidence interval (CI), 42.0% - 99.2%] sensitivity and 84.6% (95% CI, 53.7% - 97.3%) specificity, 71.4% (95% CI, 30.3% - 94.9%) sensitivity and 92.3% (95% CI, 62.1% - 99.6%) specificity, and 100% (95% CI, 56.1% - 100%) sensitivity and 53.9% (95% CI, 26.1% - 79.6%) specificity respectively when cross-correlated with post-operational histology. Furthermore, a machine learning-based algorithm is deployed for margin assessment in the challenging ductal carcinoma in situ tissues, and achieved 85.5% (95% CI, 75.2% - 92.2%) sensitivity and 90% (95% CI, 79.9% - 95.5%) specificity. Such results present the potential of using mutlimodal ultrasound and PAT as a high-speed and accurate method for intraoperative breast tumor margins evaluation.
| S-EPMC6703831 | biostudies-literature
Project description:Objective: Cerebral autoregulation limits the variability of cerebral blood flow (CBF) in the presence of systemic arterial blood pressure (ABP) changes. Monitoring cerebral autoregulation is important in the Neurocritical Care Unit (NCCU) to assess cerebral health. Here, our goal is to identify optimal frequency-domain near-infrared spectroscopy (FD-NIRS) parameters and apply a hemodynamic model of coherent hemodynamics spectroscopy (CHS) to assess cerebral autoregulation in healthy adult subjects and NCCU patients. Methods: In five healthy subjects and three NCCU patients, ABP oscillations at a frequency around 0.065 Hz were induced by cyclic inflation-deflation of pneumatic thigh cuffs. Transfer function analysis based on wavelet transform was performed to measure dynamic relationships between ABP and oscillations in oxy- (O), deoxy- (D), and total- (T) hemoglobin concentrations measured with different FD-NIRS methods. In healthy subjects, we also obtained the dynamic CBF-ABP relationship by using FD-NIRS measurements and the CHS model. In healthy subjects, an interval of hypercapnia was performed to induce cerebral autoregulation impairment. In NCCU patients, the optical measurements of autoregulation were linked to individual clinical diagnoses. Results: In healthy subjects, hypercapnia leads to a more negative phase difference of both O and D oscillations vs. ABP oscillations, which are consistent across different FD-NIRS methods and are highly correlated with a more negative phase difference CBF vs. ABP. In the NCCU, a less negative phase difference of D vs. ABP was observed in one patient as compared to two others, indicating a better autoregulation in that patient. Conclusions: Non-invasive optical measurements of induced phase difference between D and ABP show the strongest sensitivity to cerebral autoregulation. The results from healthy subjects also show that the CHS model, in combination with FD-NIRS, can be applied to measure the CBF-ABP dynamics for a better direct measurement of cerebral autoregulation.
| S-EPMC8637213 | biostudies-literature
Project description:PurposeTo demonstrate the application of phase-variance optical coherence tomography (pvOCT) for contrast agent-free in vivo imaging of volumetric retinal microcirculation in the human foveal region and for extraction of foveal avascular zone dimensions.MethodsA custom-built, high-speed Fourier-domain OCT retinal imaging system was used to image retinas of two healthy subjects and eight diabetic patients. Through the acquisition of multiple B-scans for each scan location, phase differences between consecutive scans were extracted and used for phase-variance contrast, identifying motion signals from within blood vessels and capillaries. The en face projection view of the inner retinal layers segmented out from volumetric pvOCT data sets allowed visualization of a perfusion network with the foveal avascular zone (FAZ). In addition, the authors presented 2D retinal perfusion maps with pseudo color-coded depth positions of capillaries.ResultsRetinal vascular imaging with pvOCT provides accurate measurements of the FAZ area and its morphology and a volumetric perfusion map of microcapillaries. In this study using two images from each fundus fluorescein angiography (FA) and pvOCT, the measured average areas of the FAZ from two healthy subjects were below 0.22 mm(2), and each of eight diabetic patients had an enlarged FAZ area, larger than 0.22 mm(2). Moreover, the FAZ areas demonstrated a significant correlation (r = 0.91) between measurements from FA and pvOCT.ConclusionsThe high-speed pvOCT allows contrast agent-free visualization of capillary networks in the human foveal region that is analogous to fundus FA imaging. This could allow for noninvasive diagnosis and progression monitoring of diabetic retinopathy in clinical settings.
| S-EPMC3292386 | biostudies-literature
Project description:BACKGROUND:Marmosets are a powerful, emerging model for human behavior and neurological disorders. However, longitudinal imaging modalities that visualize both cellular structure and function within the cortex are not available in this animal model. Hence, we implemented an approach to quantify vascular topology, hemodynamics, and neural activity in awake marmosets using two-photon microscopy (2PM). NEW METHOD:Marmosets were acclimated to a custom stereotaxic system. AAV1-GCaMP5G was injected into somatosensory cortex to optically indicate neural activity, and a cranial chamber was implanted. RESULTS:Longitudinal 2PM revealed vasculature and neurons 500?m below the cortical surface. Vascular response and neural activity during sensory stimulation were preserved over 5 and 3 months, respectively, before optical quality deteriorated. Vascular remodeling including increased tortuosity and branching was quantified. However, capillary connectivity from arterioles to venules remained unchanged. Further, behavioral assessment before and after surgery demonstrated no impact on cognitive and motor function. Immunohistochemistry confirmed minimal astrocyte activation with no focal damage. Over 6 months, total cortical depth visualized decreased. When under anesthesia, the most prominent isoflurane-induced vasodilation occurred in capillaries and smaller arterioles. COMPARISON WITH EXISTING METHOD(S):These results demonstrate the capability to repeatedly observe cortical physiology in awake marmosets over months. CONCLUSIONS:This work provides a novel and insightful technique to investigate critical mechanisms in neurological disorders in awake marmosets without introducing confounds from anesthesia.
| S-EPMC5003758 | biostudies-literature
Project description:We applied high-speed photoacoustic microscopy (PAM) for both cortical microenvironment studies and dynamic brain studies, with micrometer-level optical resolution and a millisecond-level cross-sectional imaging speed over a millimeter-level field of view. We monitored blood flow redistribution in mini-stroke mouse models and cerebral autoregulation induced by a vasoactive agent. Our results collectively suggest that high-speed PAM is a promising tool for understanding dynamic neurophysiological phenomena, complementing conventional imaging modalities.
| S-EPMC5576888 | biostudies-literature
Project description:BackgroundLow-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia.ResultsWe developed a miniature tFUS headgear, operating at 600 kHz, which can be attached to the skull of Sprague-Dawley rats through an implanted pedestal, allowing the ultrasound to be transcranially delivered to motor cortical areas of unanesthetized freely-moving rats. Video recordings were obtained to monitor physical responses from the rat during acoustic brain stimulation. The stimulation elicited body movements from various areas, such as the tail, limbs, and whiskers. Movement of the head, including chewing behavior, was also observed. When compared to the light ketamine/xylazine and isoflurane anesthetic conditions, the response rate increased while the latency to stimulation decreased in the awake condition. The individual variability in response rates was smaller during the awake condition compared to the anesthetic conditions. Our analysis of latency distribution of responses also suggested possible presence of acoustic startle responses mixed with stimulation-related physical movement. Post-tFUS monitoring of animal behaviors and histological analysis performed on the brain did not reveal any abnormalities after the repeated tFUS sessions.ConclusionsThe wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.
| S-EPMC6146769 | biostudies-literature
Project description:Endoscopic integrated photoacoustic and ultrasound imaging has the potential for early detection of the cancer in the gastrointestinal tract. Currently, slow imaging speed is one of the limitations for clinical translation. Here, we developed a high speed integrated endoscopic PA and US imaging system, which is able to perform PA and US imaging simultaneously up to 50 frames per second. Using this system, the architectural morphology and vasculature of the rectum wall were visualized from a Sprague Dawley rat in-vivo.
| S-EPMC6707714 | biostudies-literature