Evaluation of Hemodynamics in a Murine Hindlimb Ischemia Model Using Spatial Frequency Domain Imaging.

BACKGROUND AND OBJECTIVES: Spatial frequency domain imaging (SFDI), an optical imaging technique capable of quantitatively measuring tissue hemodynamics over a large field-of-view, has captured the interest of scientists and clinicians due to its ability to image rapidly and noninvasively. The goal of this study was to apply SFDI in a preclinical murine model to assess its ability to measure hemodynamic changes due to hindlimb ischemia in vivo longitudinally. STUDY DESIGN/MATERIALS AND METHODS: Complete unilateral femoral artery ligation was performed on a total of nine C57BL/6J mice to induce ischemia in the left hindlimb. Changes in vascular perfusion in each mouse were monitored through SFDI acquisition of both the ischemic and control limbs throughout the course of 4 weeks. High-frequency pulsed-wave Doppler ultrasound was also acquired to confirm occlusion of the left femoral artery post-ligation compared with the control limb, while histological analysis was used to quantify femoral artery lumen shape and size. RESULTS: Tissue oxygen saturation in the ischemic limb normalized to the control limb decreased from a ratio of 0.96 ± 0.06 at baseline to 0.86 ± 0.10 at day 1, then 0.94 ± 0.06 at day 3, followed by 0.95 ± 0.14 at day 7, 0.91 ± 0.09 at day 14, 0.90 ± 0.09 at day 21, and 1.01 ± 0.09 at day 28. CONCLUSION: The results of this study indicate the utility of SFDI to detect hemodynamic changes in a preclinical murine model, as well as how to effectively use this tool to extract information regarding ischemia-induced hindlimb changes. In our model, we observed a decline in tissue oxygen saturation within one day post-ischemic injury, followed by a return to baseline values over the 4-week study period. While reducing skin artifacts and modifying camera hardware could still improve this murine imaging approach, our multimodality study presented here suggests that SFDI can be used to reliably characterize ischemia-mediated changes in a clinically relevant mouse model of peripheral arterial disease. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Automatic Segmentation for Analysis of Murine Cardiac Ultrasound and Photoacoustic Image Data Using Deep Learning.

OBJECTIVE: Although there are methods to identify regions of interest (ROIs) from echocardiographic images of myocardial tissue, they are often time-consuming and difficult to create when image quality is poor. Further, while myocardial strain from ultrasound (US) images can be estimated, US alone cannot obtain functional information, such as oxygen saturation (sO2). Photoacoustic (PA) imaging, however, can be used to quantify sO2 levels within tissue non-invasively. METHODS: Here, we leverage deep learning methods to improve segmentation of the anterior wall of the left ventricle and apply both strain and oxygen saturation analysis via segmentation of murine US and PA images. RESULTS: Data revealed that training on US/PA images using a U-Net deep neural network can be used to create reproducible ROIs of the anterior wall of the left ventricle in a murine image dataset. Accuracy and Dice score metrics were used to evaluate performance of the neural network on each image type. We report an accuracy of 97.3% and Dice score of 0.84 for ultrasound, 95.6% and 0.73 for photoacoustic, and 96.5% and 0.81 for combined ultrasound and photoacoustic images. CONCLUSION: Rapid segmentation via such methods can assist in quantification of strain and oxygenation.

Neurovascular Hypoxia Trajectories Assessed by Photoacoustic Imaging in a Murine Model of Cardiac Arrest and Resuscitation.

Cardiac arrest is a common cause of death annually mainly due to postcardiac arrest syndrome that leads to multiple organ global hypoxia and dysfunction after resuscitation. The ability to quantify vasculature changes and tissue oxygenation is crucial to adapt patient treatment in order to minimize major outcomes after resuscitation. For the first time, we applied high-resolution ultrasound associated with photoacoustic imaging (PAI) to track neurovascular oxygenation and cardiac function trajectories in a murine model of cardiac arrest and resuscitation. We report the preservation of brain oxygenation is greater compared to that in peripheral tissues during the arrest. Furthermore, distinct patterns of cerebral oxygen decay may relate to the support of vital brain functions. In addition, we followed trajectories of cerebral perfusion and cardiac function longitudinally after induced cardiac arrest and resuscitation. Volumetric cerebral oxygen saturation (sO2) decreased 24 h postarrest, but these levels rebounded at one week. However, systolic and diastolic cardiac dysfunction persisted throughout and correlated with cerebral hypoxia. Pathophysiologic biomarker trends, identified via cerebral PAI in preclinical models, could provide new insights into understanding the pathophysiology of cardiac arrest and resuscitation.

Neurovascular hypoxia after mild traumatic brain injury in juvenile mice correlates with heart-brain dysfunctions in adulthood.

AIM: Retrospective studies suggest that mild traumatic brain injury (mTBI) in pediatric patients may lead to an increased risk of cardiac events. However, the exact functional and temporal dynamics and the associations between heart and brain pathophysiological trajectories are not understood. METHODS: A single impact to the left somatosensory cortical area of the intact skull was performed on juvenile mice (17 days postnatal). Cerebral 3D photoacoustic imaging was used to measure the oxygen saturation (sO2 ) in the impacted area 4 h after mTBI followed by 2D and 4D echocardiography at days 7, 30, 90, and 190 post-impact. At 8 months, we performed a dobutamine stress test to evaluate cardiac function. Lastly, behavioral analyses were conducted 1 year after initial injury. RESULTS: We report a rapid and transient decrease in cerebrovascular sO2 and increased hemoglobin in the impacted left brain cortex. Cardiac analyses showed long-term diastolic dysfunction and a diminished systolic strain response under stress in the mTBI group. At the molecular level, cardiac T-p38MAPK and troponin I expression was pathologic modified post-mTBI. We found linear correlations between brain sO2 measured immediately post-mTBI and long-term cardiac strain after 8 months. We report that initial cerebrovascular hypoxia and chronic cardiac dysfunction correlated with long-term behavioral changes hinting at anxiety-like and memory maladaptation. CONCLUSION: Experimental juvenile mTBI induces time-dependent cardiac dysfunction that corresponds to the initial neurovascular sO2 dip and is associated with long-term behavioral modifications. These imaging biomarkers of the heart-brain axis could be applied to improve clinical pediatric mTBI management.

Real-time biofeedback device for gait rehabilitation of post-stroke patients.

In this work, we develop a device, called 'Walk-Even', that can provide real-time feedback to correct gait asymmetry commonly exhibited in post-stroke survivors and persons with certain neurological disorders. The device computes gait parameters, including gait time, swing time, and stance time of each leg, to detect gait asymmetry and provide corresponding real-time biofeedback by means of auditory and electrotactile stimulation to actively correct the user's gait. The system consists of customized force-sensor-embedded insoles adjustable to fit any shoe size, electrotactile and auditory feedback circuits, microcontroller, and wireless XBee transceivers. The device also offers data saving capability. To validate its accuracy and reliability, we compared the gait measurements from our device with a commercial gait and balance assessment device, Zeno Walkway. The results show good correlation and agreement in a validity study with six healthy subjects and reliability study with seventeen healthy subjects. In addition, preliminary testing on six post-stroke patients after an 8-week training shows that the Walk-Even device helps to improve gait symmetry, foot pressure and forefoot loading of the affected side. Thus, initial testing indicates that the device is accurate in measuring the gait parameters and effective in improving gait symmetry using real-time feedback. The device is portable and low cost and has the potential for use in a non-clinical setting for patients that can walk independently without assistance. A more extensive testing with stroke patients is still ongoing.