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Kothapalli, S.-R.

Publications and source records attributed to Kothapalli, S.-R..

5 recordsLinked to original sources

Simultaneous Functional Ultrasound, Intrinsic Optical Signal and Widefield Calcium Neuroimaging

Functional ultrasound (fUS) maps cerebral blood volume (CBV) but lacks molecular and neuronal specificity. By simultaneously integrating fUS with optical imaging, we show that fUS-derived CBV correlates with both optically measured hemoglobin and neuronal calcium activity in awake mice. We further derive hemodynamic response functions linking calcium activity to CBV during spontaneous and sensory-evoked activity. Application to a mouse glioblastoma model demonstrates utility for studying neurovascular dysfunction in complex neuropathologies.

neuroscience↗

Integrated Ultrasound Neuromodulation and Optical Neuroimaging in Awake Mice using a Transparent Ultrasound Transducer Cranial Window

Ultrasound neuromodulation is a rapidly advancing, non-invasive technique with significant therapeutic potential for treating various neurological disorders. Although extensive in vitro and in vivo studies have provided valuable insights into its modulatory effects, the underlying mechanisms remain poorly understood, limiting its clinical translation. Optical neuroimaging techniques can help investigate these mechanisms; however, the opacity and bulkiness of conventional ultrasound transducers pose significant challenges for their integration with in vivo ultrasound neuromodulation studies, particularly in awake rodents. To address these limitations, we propose a straightforward solution: a miniaturized lithium niobate-based transparent ultrasound transducer (TUT) integrated as a thinned-skull cranial window for ultrasound stimulation while facilitating multimodal optical neuroimaging in awake mice brain. Using laser speckle contrast imaging and intrinsic optical signal imaging, we studied changes in brain hemodynamics in response to various ultrasound stimulation sequences. Our experiments demonstrated that TUT cranial window can robustly induce neuromodulatory effects with observed increase in both cerebral blood flow and total hemoglobin, with peak and cumulative hemodynamic changes directionally correlated with ultrasound stimulation duration and intensity. Overall, these findings highlight that TUT cranial window can seamlessly integrate ultrasound stimulation and optical neuroimaging in awake mouse brain models, offering promising prospects for uncovering the underlying mechanisms of ultrasound neuromodulation.

neuroscience↗

Awake mouse brain photoacoustic and optical imaging through a transparent ultrasound cranial window

Optical resolution photoacoustic microscopy (OR-PAM) can map the cerebral vasculature at capillary level resolution. However, the OR-PAM setups bulky imaging head makes awake mouse brain imaging challenging and inhibits its integration with other optical neuroimaging modalities. Moreover, the glass cranial windows used for optical microscopy are unsuitable for OR-PAM due to the acoustic impedance mismatch between the glass plate and the tissue. To overcome these challenges, we propose a lithium niobate based transparent ultrasound trans-ducer (TUT) as a cranial window on a thinned mouse skull. The TUT cranial window simplifies the imaging head considerably due to its dual functionality as an optical window and ultrasound transducer. The window remains stable for six weeks, with no noticeable inflammation and minimal bone regrowth. The TUT windows potential is demonstrated by imaging the awake mouse cerebral vasculature using OR-PAM, intrinsic optical signal imaging and two-photon microscopy. The TUT cranial window can potentially also be used for ultrasound stimulation and simultaneous multimodal imaging of the awake mouse brain.

bioengineering↗

A Transparent Ultrasound Array for Real-time Optical, Ultrasound and Photoacoustic Imaging

Objective and Impact StatementSimultaneous imaging of ultrasound and optical contrasts can help map structural, functional and molecular biomarkers inside living subjects with high spatial resolution. There is a need to develop a platform to facilitate this multimodal imaging capability to improve diagnostic sensitivity and specificity. IntroductionCurrently, combining ultrasound, photoacoustic and optical imaging modalities is challenging because con-ventional ultrasound transducer arrays are optically opaque. As a result, complex geometries are used to co-align both optical and ultrasound waves in the same field of view. MethodsOne elegant solution is to make the ultrasound transducer transparent to light. Here, we demonstrate a novel transparent ultrasound transducer (TUT) liner array fabricated using a transparent lithium niobate piezoelectric material for real-time multimodal imaging. ResultsThe TUT array consisted of 64 elements and centered at [~] 6 MHz frequency. We demonstrate a quad-mode ultrasound, Doppler ultrasound, photoacoustic and fluorescence imaging in real-time using the TUT array directly coupled to the tissue mimicking phantoms. ConclusionThe TUT array successfully showed a multimodal imaging capability, and has potential applications in diagnosing cancer, neuro and vascular diseases, including image-guided endoscopy and wearable imaging.

bioengineering↗

Modeling Combined Ultrasound and Photoacoustic Imaging: Simulations aiding Device Development and Deep Learning

Combined ultrasound and photoacoustic (USPA) imaging has attracted several clinical applications due to its ability to simultaneously display structural and molecular information of deep biological tissue in real time. However, the depth dependent optical attenuation and the unknown optical and acoustic heterogeneities, limit the USPA imaging performance, especially from deeper tissue regions. Novel instrumentation, image reconstruction and deep learning methods are currently being explored to improve the USPA image quality. Effective implementation of these approaches requires a reliable USPA simulation tool capable of generating US based anatomical and PA based molecular information. Here, we developed a hybrid USPA simulation platform by integrating finite element models of light and ultrasound propagation. The feasibility of modeling US combined with optical fluence dependent multispectral PA imaging is demonstrated using in silico homogeneous and heterogeneous prostate tissue. The platform allows optimization of device design parameters, such as the aperture size and frequency of light source and ultrasound detector arrays. In addition, the potential of this simulation platform to generative massive USPA datasets aiding the data driven deep-learning enhanced USPA imaging has been validated using both simulations and experiments.

bioengineering↗