The increasing use of mouse models for human brain disease studies presents an emerging need for a new functional imaging modality. Using optical excitation and acoustic detection, we developed a functional connectivity photoacoustic tomography system, which allows noninvasive imaging of resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight functional regions, including the olfactory bulb, limbic, parietal, somatosensory, retrosplenial, visual, motor, and temporal regions, as well as in several subregions. The borders and locations of these regions agreed well with the Paxinos mouse brain atlas. By subjecting the mouse to alternating hyperoxic and hypoxic conditions, strong and weak functional connectivities were observed, respectively. In addition to connectivity images, vascular images were simultaneously acquired. These studies show that functional connectivity photoacoustic tomography is a promising, noninvasive technique for functional imaging of the mouse brain.fcPAT | RSFC | mouse brain functional imaging | hyperoxia | hypoxia

We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively decoupled by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area had a clear vascular pattern and spread wider than the somatosensory region. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

Photoacoustic imaging (PAI) is an emerging medical imaging modality capable of providing high spatial resolution of Ultrasound (US) imaging and high contrast of optical imaging. Delay-and-Sum (DAS) is the most common beamforming algorithm in PAI. However, using DAS beamformer leads to low resolution images and considerable contribution of off-axis signals. A new paradigm namely delay-multiply-and-sum (DMAS), which was originally used as a reconstruction algorithm in confocal microwave imaging, was introduced to overcome the challenges in DAS. DMAS was used in PAI systems and it was shown that this algorithm results in resolution improvement and sidelobe degrading. However, DMAS is still sensitive to high levels of noise, and resolution improvement is not satisfying. Here, we propose a novel algorithm based on DAS algebra inside DMAS formula expansion, double stage DMAS (DS-DMAS), which improves the image resolution and levels of sidelobe, and is much less sensitive to high level of noise compared to DMAS. The performance of DS-DMAS algorithm is evaluated numerically and experimentally. The resulted images are evaluated qualitatively and quantitatively using established quality metrics including signal-to-noise ratio (SNR), full-width-half-maximum (FWHM) and contrast ratio (CR). It is shown that DS-DMAS outperforms DAS and DMAS at the expense of higher computational load. DS-DMAS reduces the lateral valley for about 15 dB and improves the SNR and FWHM better than 13% and 30%, respectively. Moreover, the levels of sidelobe are reduced for about 10 dB in comparison with those in DMAS.

Spontaneous fluctuations of resting state functional MRI (rsfMRI) have been widely used to understand the macro-connectome of the human brain. However, these fluctuations are not synchronized among subjects, which leads to limitations and makes utilization of first-level model-based methods challenging. Considering this limitation of rsfMRI data in the time domain, we propose to transfer the spatiotemporal information of the rsfMRI data to another domain, the connectivity domain, in which each value represents the same effect across subjects. Using a set of seed networks and a connectivity index to calculate the functional connectivity for each seed network, we transform data into the connectivity domain by generating connectivity weights for each subject. Comparison of the two domains using a data-driven method suggests several advantages in analyzing data using data-driven methods in the connectivity domain over the time domain. We also demonstrate the feasibility of applying model-based methods in the connectivity domain, which offers a new pathway for the use of first-level model-based methods on rsfMRI data. The connectivity domain, furthermore, demonstrates a unique opportunity to perform first-level feature-based data-driven and model-based analyses. The connectivity domain can be constructed from any technique that identifies sets of features that are similar across subjects and can greatly help researchers in the study of macro-connectome brain function by enabling us to perform a wide range of model-based and data-driven approaches on rsfMRI data, decreasing susceptibility of analysis techniques to parameters that are not related to brain connectivity information, and evaluating both static and dynamic functional connectivity of the brain from a new perspective.