Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy

High-speed high-resolution imaging of the whole-brain hemodynamics is urgently needed to facilitate the next level of neurovascular research. Image acquisition speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, and displaying fast pathophysiological dynamics on a micro and macro-level, enabling advances in current queries in neurovascular and brain metabolism research, including stroke, dementia and acute brain injury. Further, real-time oxygen saturation of hemoglobin (sO2) imaging to differentiate arteries from veins and capture fast-paced oxygen delivery dynamics is needed to solve pertinent questions in these fields and beyond. Here, we present a novel ultrafast functional photoacoustic microscopy (UFF-PAM) to image the whole-brain hemodynamics and oxygen delivery. UFF-PAM takes advantage of several key engineering innovations, including Raman-shifter-based dual-wavelength laser excitation, water-immersible 12-facet-polygon scanner, high-sensitivity ultrasound transducer, and deep-learning-based image upsampling. A volumetric imaging rate of 2 Hz has been achieved over a field of view (FOV) of 11× 7.5 × 1.5 mm3 with a high spatial resolution of ~10 µm. Using the UFF-PAM system, we have demonstrated proof-of-concept functional studies on the mouse brains in response to systemic hypoxia, sodium nitroprusside, and stroke. We observed the mouse brain’s fast morphological and functional changes over the entire cortex, including vasoconstriction, vasodilation, and deoxygenation. More interestingly, for the first time, under the whole-brain FOV and micro-vessel resolution, we captured the vasoconstriction and oxygenation change simultaneously in the spreading depolarization (SD) wave. Our work provides a great potential for fundamental brain research under various pathological and physiological conditions.

Ultrasonographic Changes in Brain Hemodynamics in Patients with Parkinson’s Disease and Risk Factors for Cerebrovascular Disease: A Pilot Study

Recent epidemiological studies have revealed a correlation between atypical features and worse functional outcomes in Parkinson’s disease (PD) patients with cerebrovascular disease (CVD). We aimed to evaluate the brain hemodynamics of PD patients with risk factors for CVD using Doppler ultrasonography. In this prospective pilot study, we randomly included 27 outpatients diagnosed with PD. Transcranial color-coded sonography (TCCS) examinations were performed, obtaining measurements of middle cerebral artery mean flow velocities (Vm), the resistance index (RI), and the pulsatility index (PI). The breath-holding index (BHI) was used to assess cerebrovascular reactivity (cVR). Standardized functional scales (UPDRS III, Hoehn & Yahr scale, and MoCA) were administered. The patients were divided into two groups: those with two or more vascular risk factors (PDvasc) and those with fewer than two vascular risk factors (PDnvasc). Patients in the PDvasc group showed higher PI (1.00 vs. 0.85; p = 0.020 ), RI (0.59 vs. 0.5; p = 0.05 ), H&Y mean (2.4 vs. 1.4; p = 0.036 ), higher frequency of altered cVR (90.9% vs. 25.0%; p = 0.001 ), and lower BHI (0.46 vs. 1.01; p = 0.027 ). We also divided the patients in other two groups: one with patients with classical and another with akinetic-rigid PD clinical type. Patients with the akinetic-rigid type of PD had significantly higher RI (0.60 vs. 0.51; p = 0.03 ), PI (0.99 vs. 0.77; p = 0.03 ), higher frequency of altered cVR (80% vs. 35%; p = 0.02 ), and lower BHI (0.48 vs. 0.96; p = 0.05 ) than patients with classic-type PD. We concluded that TCCS displays impaired cerebrovascular reactivity and a more severe disease pattern in Parkinsonian patients with two or more risk factors for CVD and in the akinetic-rigid type. Doppler ultrasonography may be a useful tool in a clinical setting to investigate PD patients.

Hemodynamics disorders in vertebra-basilar region in patients with vibration disease, caused by local vibration (data of rheography and transcranial dopplerography)

Brain hemodynamics was studied in vertebra-basilar region in patients with vibration disease, resulting from local vibration. High percentage of clinical and roentgenologic manifestations of cervical octeochondrosis was revealed, as well as incidence increase of cephalgia syndrome while vibration disease progressing. Analysis of rheographic curves (deviation by E.Enin) and transcranial dopplerosonograms showed cerebral circulation dificiency in vertebrabasilar region. The highest level of hemodynamic disorders was marked in vertebral arteries. It is not excluded, that one of the factors, enfluencing hemodynamics disorders, is pathology of the vertebral column.

Multimodal Autoencoder Predicts fNIRS Resting State From EEG Signals

In this work, we introduce a deep learning architecture for evaluation on multimodal electroencephalographic (EEG) and functional near-infrared spectroscopy (fNIRS) recordings from 40 epileptic patients. Long short-term memory units and convolutional neural networks are integrated within a multimodal sequence-to-sequence autoencoder. The trained neural network predicts fNIRS signals from EEG, sans a priori, by hierarchically extracting deep features from EEG full spectra and specific EEG frequency bands. Results show that higher frequency EEG ranges are predictive of fNIRS signals with the gamma band inputs dominating fNIRS prediction as compared to other frequency envelopes. Seed based functional connectivity validates similar patterns between experimental fNIRS and our model’s fNIRS reconstructions. This is the first study that shows it is possible to predict brain hemodynamics (fNIRS) from encoded neural data (EEG) in the resting human epileptic brain based on power spectrum amplitude modulation of frequency oscillations in the context of specific hypotheses about how EEG frequency bands decode fNIRS signals.

Hemodynamic Response to Three Types of Urban Spaces before and after Lockdown during the COVID-19 Pandemic

(1) Background: Prolonged lockdowns with stay-at-home orders have been introduced in many countries since the outbreak of the COVID-19 pandemic. They have caused a drastic change in the everyday lives of people living in urbanized areas, and are considered to contribute to a modified perception of the public space. As research related to the impact of COVID-19 restrictions on mental health and well-being emerges, the associated longitudinal changes of brain hemodynamics in healthy adults remain largely unknown. (2) Methods: this study examined the hemodynamic activation patterns of the prefrontal and occipital cortices of 12 participants (5 male, Mage = 47.80, SDage = 17.79, range 25 to 74, and 7 female, Mage = 39.00, SDage = 18.18, range 21 to 65) passively viewing videos from three urban sites in Singapore (Urban Park, Neighborhood Landscape and City Center) at two different time points—T1, before the COVID-19 pandemic and T2, soon after the lockdown was over. (3) Results: We observed a significant and marginally significant decrease in average oxyhemoglobin (Oxy-Hb) over time for each of the visual conditions. For both green spaces (Urban Park and Neighborhood Landscape), the decrease was in the visual cortex, while for the City Center with no green elements, the marginal decrease was observed in the visual cortex and the frontal eye fields. (4) Conclusions: The results suggest that the COVID-19-related lockdown experienced by urban inhabitants may have contributed to decreased brain hemodynamics, which are further related to a heightened risk of mental health disorders, such as depression or a decline in cognitive functions. Moreover, the busy City Center scenes induced a hemodynamic pattern associated with stress and anxiety, while urban green spaces did not cause such an effect. Urban green scenes can be an important factor to offset the negative neuropsychological impact of busy urban environments post-pandemic.

A Skull-Removed Chronic Cranial Window for Ultrasound and Photoacoustic Imaging of the Rodent Brain

Ultrasound and photoacoustic imaging are emerging as powerful tools to study brain structures and functions. The skull introduces significant distortion and attenuation of the ultrasound signals deteriorating image quality. For biological studies employing rodents, craniotomy is often times performed to enhance image qualities. However, craniotomy is unsuitable for longitudinal studies, where a long-term cranial window is needed to prevent repeated surgeries. Here, we propose a mouse model to eliminate sound blockage by the top portion of the skull, while minimum physiological perturbation to the imaged object is incurred. With the new mouse model, no craniotomy is needed before each imaging experiment. The effectiveness of our method was confirmed by three imaging systems: photoacoustic computed tomography, ultrasound imaging, and photoacoustic mesoscopy. Functional photoacoustic imaging of the mouse brain hemodynamics was also conducted. We expect new applications to be enabled by the new mouse model for photoacoustic and ultrasound imaging.

Hearing brain evaluated using near-infrared spectroscopy in congenital toxoplasmosis

Congenital toxoplasmosis (CT) is a known cause of hearing loss directly caused by Toxoplasma gondii. Hearing loss might result from sensory, neural, or sensorineural lesions. Early treated infants rarely develop hearing loss, but retinochoroidal lesions, intracranial calcifications and hydrocephalus are common. In this study, we aimed to evaluate the brain evoked hemodynamic responses of CT and healthy infants during four auditory stimuli: mother infant directed speech, researcher infant directed speech, mother reading and researcher recorded. Children underwent Transitionally Evoked Otoacoustic Emission Auditory Testing and Automated Brainstem Auditory Response tests with normal auditory results, but with a tendency for greater latencies in the CT group compared to the control group. We assessed brain hemodynamics with functional near-infrared spectroscopy (fNIRS) measurements from 61 infants, and we present fNIRS results as frequency maps of activation and deactivation for each stimulus. By evaluating infants in the three first months of life, we observed an individual heterogeneous brain activation pattern in response to all auditory stimuli for both groups. Each channel was activated or deactivated in less than 30% of children for all stimuli. There is a need of prospective studies to evaluate if the neurologic or auditory changes course with compromise of children outcomes.