Publications

2025

1. Biomed. Opt. Express

   Evaluation of radio frequency ablation in human left atrial tissues for atrial fibrillation using optical coherence tomography

   Ebenezer Raj Selvaraj Mercyshalinie, Dylan O. Patterson, Bornface M. Mutembei, Avery D. Ladymon, Feng Yan, Kaustubh Pandit, Hayden Peek, Kar-Ming A. Fung, Qinghao Zhang, Chen Wang, Yan Cui, Junyuan Liu, Ronghao Liu, Paulo Martins, Stavros Stavrakis, Ke Zhang, David R. Miller, and Qinggong Tang

   Biomed. Opt. Express, Oct 2025

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   Despite its widespread adoption, the success of radiofrequency (RF) ablation is often limited by challenges in achieving durable, transmural lesions while avoiding complications such as incomplete ablation or over-ablation. Optical coherence tomography (OCT) offers high-resolution visualization of cardiac tissue, enabling real-time assessment of lesion depth. Therefore, we investigated the impact of RF ablation on donated human left atrial tissue using an OCT imaging system to assess lesion formation in a controlled laboratory setting. RF ablation lesions were created at durations of 20, 40, 60, 80, and 100 seconds (s), and their effects were quantified by calculating the attenuation coefficient from OCT images. To identify tissue regions in the image, a U-Net model was employed for segmentation, achieving a mean intersection over union (IoU) of 0.9748 with an inference time of 82 milliseconds. Our results demonstrated clear differences in tissue response before and after ablation, with distinct lesion characteristics across the tested durations. One-way ANOVA analysis yielded a p-value of 1.09 × 10−8, confirming statistically significant differences among the ablation durations. These findings highlight the potential of SD-OCT for precise, real-time monitoring of ablation effects. Future work aims to integrate OCT with ablation catheters for clinical applications, enhancing the precision of catheter-based treatments for conditions like atrial fibrillation.

2. Advanced Science

   A Minimally Invasive Framework Reveals Region-Specific Cerebrovascular Remodeling in Aging Using Intravital Functional Ultrasound Imaging and Ultrasound Localization Microscopy (fUS-ULM)

   Sharon Negri, Adam Nyul-Toth, Madison Milan, Eva Troyano-Rodriguez, Sherwin Tavakol, Jennifer Ihuoma, Zeke Reyff, Rakesh Rudraboina, Rafal Gulej, Raymond Jang, Anna Csiszar, Zoltan Ungvari, Audrey Cleuren, David R Miller, Andriy Yabluchanskiy, Mickael Tanter, and Stefano Tarantini

   Advanced Science, Sep 2025

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   Abstract Aging impairs cerebrovascular structure and function, contributing to cognitive decline and dementia. Here, a novel, high-resolution, intravital imaging platform is presented that combines functional ultrasound (fUS) and ultrasound localization microscopy (ULM) through a chronically implanted, polymethylpentene (TPX) cranial window, a transparent implant that enables ultrasound imaging through the skull. This approach enables intravital, longitudinal, minimally invasive assessment of cerebrovascular structure and function across cortical and deep brain regions. Leveraging this platform, a new method is developed to estimate resting cerebral blood flow (CBF) by integrating microbubble (MB) velocity data from fUS with microvascular geometry derived from ULM. Notably, a significant age-related decline in the cortical arteriole-to-venule ratio (AVR) is discovered, introducing a novel biomarker of structural cerebrovascular remodeling. It is also validated that fUS can reliably assess neurovascular coupling (NVC) responses in aged mice. This study establishes a powerful, non-invasive, and repeatable investigative tool for future preclinical studies aimed at evaluating the efficacy of therapeutic interventions targeting vascular contributions to cognitive impairment and neurodegeneration.

2024

1. World Neurosurgery: X

   Laser speckle contrast imaging versus microvascular Doppler sonography in aneurysm surgery: A prospective study

   Alexis Dimanche, Johannes Goldberg, David R. Miller, David Bervini, Andreas Raabe, and Andrew K. Dunn

   World Neurosurgery: X, Jul 2024

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   Objective This study aimed to compare microvascular Doppler sonography (MDS) and laser speckle contrast imaging (LSCI) for assessing vessel patency and aneurysm occlusion during microsurgical clipping of intracranial aneurysms. Methods MDS and LSCI were used after clip placement during six neurovascular procedures including six patients, and agreement between the two techniques was assessed. LSCI was performed in parallel or right after MDS evaluation. The Doppler response was assessed through listening while flow in the LSCI videos was evaluated by three blinded neurovascular surgeons after the surgery. Statistical analysis determined the agreement between the techniques in assessing flow in 18 regions of interest (ROIs). Results Agreement between MDS and LSCI in assessing vessel patency was observed in 87 % of the ROIs. LSCI accurately identified flow in 93.3 % of assessable ROIs, with no false positive or negative measurements. Three ROIs were not assessable with LSCI due to motion artifacts or poor image quality. No complications were observed. Conclusions LSCI demonstrated high agreement with MDS in assessing vessel patency during microsurgical clipping of intracranial aneurysms. It provided continuous, real-time, full-field imaging with high spatial resolution and temporal resolution. While MDS allowed evaluation of deep vascular regions, LSCI complemented it by offering unlimited assessment of surrounding vessels.

2. Optica Biophotonics Congress

   Imaging partial pressure of oxygen using three-photon microscopy at 1670 nm

   Mohammed Alfadhel, Thomas Troxler, Srinivasa Rao Allu, Luca Ravotto, Qi Pian, Buyin Fu, Steven Hou, David R. Miller, Mohammad A. Yaseen, Sergei A. Vinogradov, and Sava Sakadzic

   In Optica Biophotonics Congress: Biomedical Optics 2024 (Translational, Microscopy, OCT, OTS, BRAIN), Jul 2024

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   Three-photon microscopy shows potential to probe much deeper brain structures than previously possible with two-photon microscopy. Here we demonstrate the first intravascular measurements of pO2 in subcortical vasculature in awake mice using three-photon phosphorescence lifetime microscopy (3PLM) and a phosphorescent probe Oxyphor 2P.

3. Neurosurgery

   Intraoperative laser speckle contrast imaging to assess vessel flow in neurosurgery: a pilot study

   Johannes Goldberg, David R Miller, Alexis Dimanche, Cédric Kissling, Timothy Müller, Mandy D Müller, Christopher Marvin Jesse, Michael Murek, David Bervini, Andrew K Dunn, and others

   Neurosurgery, May 2024

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2023

1. Frontiers in Surgery

   Continuous hemodynamics monitoring during arteriovenous malformation microsurgical resection with laser speckle contrast imaging: case report

   Alexis Dimanche, David R. Miller, Johannes Goldberg, Andreas Raabe, Andrew K. Dunn, and David Bervini

   Frontiers in Surgery, Dec 2023

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   AVM surgery is challenging due to progressive and often unforeseeable flow changes during its resection which involve both the AVM and the surrounding brain tissue. Hence, accurate monitoring of blood flow is crucial to minimize complications and improve outcomes. The following case report illustrates the usefulness of complimentary non-invasive tools that can provide real time blood flow assessment. We present a case demonstrating the application of laser speckle contrast imaging (LSCI) in evaluating vessel flow dynamics during AVM surgery. A 30-year-old female presented with sudden headaches, nausea, vomiting, and vertigo. Emergency imaging revealed a ruptured cerebellar AVM necessitating surgical intervention. LSCI was integrated into the surgical workflow, providing continuous visualization of relative cerebral blood flow (rCBF) of vessels surrounding the AVM. Before AVM resection, LSCI measurements revealed the arterialized vasculature supplying the AVM nidus; measurements after AVM resection showed significant hemodynamic changes including normal flow in the initially arterialized AVM draining veins and adjacent arterial branches. LSCI also detected blood flow alterations during temporary occlusion, enabling assessment of downstream vascular regions. In conclusion, we provide an example supporting the utility of LSCI for real-time hemodynamic monitoring during AVM resection surgery. LSCI offers non-invasive, continuous, and immediate blood flow information, complementing conventional imaging methods like indocyanine green angiography. Additionally, our findings suggest that LSCI has the potential to provide a non-invasive means of identifying the specific superficial vessel branches or cortical areas that receive blood supply from a particular vessel.

2. Sedation with dexmedetomidine decreases skin perfusion in cats

   Danielle L. Hollenbeck, Bradley T. Simon, Elizabeth M. Scallan, Kelley M. Thieman-Mankin, David R. Miller, Andrew K. Dunn, and Vanna M. Dickerson

   American Journal of Veterinary Research, Dec 2023

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3. Considerations for Intraoperative Laser Speckle Contrast Imaging for Vessel Flow Visualization

   Alexis Dimanche, David R. Miller, and Andrew K. Dunn

   In 2023 IEEE Biomedical Circuits and Systems Conference (BioCAS), Oct 2023

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   Laser speckle contrast imaging (LSCI) has emerged as a promising non-invasive optical technique for assessing blood flow dynamics in clinical settings, including neurosurgery. This study aimed to illustrate the challenges and limitations associated with intraoperative LSCI-based blood flow assessment. A custom microscope-integrated LSCI device was utilized in 20 neurosurgical procedures, providing real-time high-resolution imaging. Two clinical observations were reported, highlighting the impact of static scattering and limited penetration depth on LSCI measurements. Calcified vessel walls affected the speckle contrast values, emphasizing the importance of precise thresholding for meaningful blood flow visualization and intraoperative display. Furthermore, LSCI demonstrated limited capability in assessing blood flow within thick vessels such as the carotid artery. The results shed light on the potential applications and limitations of LSCI in surgical interventions, emphasizing the need for further research. Overall, LSCI shows promise as a valuable tool for evaluating tissue perfusion and vessel flow, but careful consideration of its limitations is crucial for successful implementation in clinical practice.

4. Multi-modal microvascular cerebral blood flow velocity mapping with 14T single-vessel MRI and optical microscopy in the mouse brain

   D. R. Miller, X. A. Zhou, S. Liang, Z. Xie, B. Fu, P. Shin, Q. Pian, Y. Jiang, A. Liu, J. Tang, A. Devor, X. Yu, and S. Sakadzic

   bioRxiv, Nov 2023

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   In this study, we imaged the same penetrating cortical vessels in a mouse using ultrahigh field single-vessel MRI at 14 T and high-resolution optical microscopy imaging. The optical imaging was performed through a chronic sealed cranial window, while the single-vessel MRI was facilitated by a custom-designed, chronically implanted radiofrequency coil surrounding the window. The MRI and optical imaging were performed sequentially focused on the same penetrating cortical arterioles and surfacing venules within the whisker barrel cortex. With MRI, we obtained high-resolution multi-gradient echo (MGE) images and single-vessel phase contrast (PC) velocity maps. With optical imaging, we acquired microvascular angiograms using 2-Photon Microscopy (2PM) and Optical Coherence Tomography (OCT) and measured the blood flow velocity using Dynamic Light Scattering OCT (DLS-OCT). The MGE images, PC-based MRI velocity maps, OCT angiograms, and DLS-OCT velocity maps were coregistered with the 2PM microvascular angiograms. Using these tools, we cross-validated blood flow velocity in the penetrating cortical arterioles and surfacing venules measured by single-vessel MRI and OCT at rest. Our novel method demonstrates the possibility of combining ultrahigh field single-vessel MRI and high-resolution optical methods (e.g., 2PM and OCT) for studying brain structure and function with single microvessel precision.Competing Interest StatementThe authors have declared no competing interest.