Brenda Yu

All Publications

• Quantitative Profiling of the Effects of Subanesthetic Ketamine on Naturalistic Behavior and Brain Microstructure Ewbank, S., Hart, A., Muwanga, G., Gopal, D., Roy, K., Yu, B., Laurent, R., Tawfik, V., Rodriguez, C., Mcnab, J., Airan, R. SPRINGERNATURE. 2024: 104

  View details for Web of Science ID 001421429700227

• SELECTIVELY ACTIVATING THE AFFECTIVE EFFICACY OF KETAMINE VIA REGIONALLY-TARGETED NONINVASIVE ULTRASONIC DRUG UNCAGING Yu, B., Roy, K., Ewbank, S., Purohit, M., Azadian, M., Xiang, Y., Wang, J., Airan, R. SPRINGERNATURE. 2024: 411-412

  View details for Web of Science ID 001407851100297

• Ultrasonic cerebrospinal fluid clearance improves outcomes in hemorrhagic brain injury models. bioRxiv : the preprint server for biology Azadian, M. M., Macedo, N., Yu, B. J., Fame, R. M., Airan, R. D. 2024

  Abstract

  Impaired clearance of the byproducts of aging and neurologic disease from the brain exacerbates disease progression and severity. We have developed a noninvasive, low intensity transcranial focused ultrasound protocol that facilitates the removal of pathogenic substances from the cerebrospinal fluid (CSF) and the brain interstitium. This protocol clears neurofilament light chain (NfL) - an aging byproduct - in aged mice and clears red blood cells (RBCs) from the central nervous system in two mouse models of hemorrhagic brain injury. Cleared RBCs accumulate in the cervical lymph nodes from both the CSF and interstitial compartments, indicating clearance through meningeal lymphatics. Treating these hemorrhagic brain injury models with this ultrasound protocol reduced neuroinflammatory and neurocytotoxic profiles, improved behavioral outcomes, decreased morbidity and, importantly, increased survival. RBC clearance efficacy was blocked by mechanosensitive channel antagonism and was effective when applied in anesthetized subjects, indicating a mechanosensitive channel mediated mechanism that does not depend on sensory stimulation or a specific neural activity pattern. Notably, this protocol qualifies for an FDA non-significant risk designation given its low intensity, making it readily clinically translatable. Overall, our results demonstrate that this low-intensity transcranial focused ultrasound protocol clears hemorrhage and other harmful substances from the brain via the meningeal lymphatic system, potentially offering a novel therapeutic tool for varied neurologic disorders.

  View details for DOI 10.1101/2024.06.02.597001

  View details for PubMedID 38895304

  View details for PubMedCentralID PMC11185536

• High-throughput ultrasound neuromodulation in awake and freely behaving rats. Brain stimulation Di Ianni, T., Morrison, K. P., Yu, B., Murphy, K. R., de Lecea, L., Airan, R. D. 2023; 16 (6): 1743-1752

  Abstract

  Transcranial ultrasound neuromodulation is a promising potential therapeutic tool for the noninvasive treatment of neuropsychiatric disorders. However, the expansive parameter space and difficulties in controlling for peripheral auditory effects make it challenging to identify ultrasound sequences and brain targets that may provide therapeutic efficacy. Careful preclinical investigations in clinically relevant behavioral models are critically needed to identify suitable brain targets and acoustic parameters. However, there is a lack of ultrasound devices allowing for multi-target experimental investigations in awake and unrestrained rodents. We developed a miniaturized 64-element ultrasound array that enables neurointerventional investigations with within-trial active control targets in freely behaving rats. We first characterized the acoustic field with measurements in free water and with transcranial propagation. We then confirmed in vivo that the array can target multiple brain regions via electronic steering, and verified that wearing the device does not cause significant impairments to animal motility. Finally, we demonstrated the performance of our system in a high-throughput neuromodulation experiment, where we found that ultrasound stimulation of the rat central medial thalamus, but not an active control target, promotes arousal and increases locomotor activity.

  View details for DOI 10.1016/j.brs.2023.11.014

  View details for PubMedID 38052373

• Pharmacokinetics-Pharmacodynamics Dissociation Indicative of Ketamine-Induced Plasticity as Revealed by Ultrasonic Ketamine Uncaging in Rat Medial Prefrontal Cortex Yu, B., Roy, K., Purohit, M., Xiang, Y., Azadian, M., Taoube, A., Kwan, A., Lopez, D., Airan, R. SPRINGERNATURE. 2023: 277-278

  View details for Web of Science ID 001126640300117

• Acoustomechanically activatable liposomes for ultrasonic drug uncaging. bioRxiv : the preprint server for biology Purohit, M. P., Roy, K. S., Xiang, Y., Yu, B. J., Azadian, M. M., Muwanga, G., Hart, A. R., Taoube, A. K., Lopez, D. G., Airan, R. D. 2023

  Abstract

  Ultrasound-activatable drug-loaded nanocarriers enable noninvasive and spatiotemporally-precise on-demand drug delivery throughout the body. However, most systems for ultrasonic drug uncaging utilize cavitation or heating as the drug release mechanism and often incorporate relatively exotic excipients into the formulation that together limit the drug-loading potential, stability, and clinical translatability and applicability of these systems. Here we describe an alternate strategy for the design of such systems in which the acoustic impedance and osmolarity of the internal liquid phase of a drug-loaded particle is tuned to maximize ultrasound-induced drug release. No gas phase, cavitation, or medium heating is necessary for the drug release mechanism. Instead, a non-cavitation-based mechanical response to ultrasound mediates the drug release. Importantly, this strategy can be implemented with relatively common pharmaceutical excipients, as we demonstrate here by implementing this mechanism with the inclusion of a few percent sucrose into the internal buffer of a liposome. Further, the ultrasound protocols sufficient for in vivo drug uncaging with this system are achievable with current clinical therapeutic ultrasound systems and with intensities that are within FDA and society guidelines for safe transcranial ultrasound application. Finally, this current implementation of this mechanism should be versatile and effective for the loading and uncaging of any therapeutic that may be loaded into a liposome, as we demonstrate for four different drugs in vitro, and two in vivo. These acoustomechanically activatable liposomes formulated with common pharmaceutical excipients promise a system with high clinical translational potential for ultrasonic drug uncaging of myriad drugs of clinical interest.

  View details for DOI 10.1101/2023.10.23.563690

  View details for PubMedID 37961368

  View details for PubMedCentralID PMC10634775

• Ketogenic Diet as a Metabolic Therapy for Bipolar Disorder: Clinical Developments Journal of Affective Disorders Reports Yu , B., Oz, R., Sethi, S. 2022

  View details for DOI 10.1016/j.jadr.2022.100457

• Increasing Diversity in Radiology and Molecular Imaging: Current Challenges. Molecular imaging and biology Fite, B. Z., Hinostroza, V. n., States, L. n., Hicks-Nelson, A. n., Baratto, L. n., Kallianos, K. n., Codari, M. n., Yu, B. n., Jha, P. n., Shams, M. n., Stoyanova, T. n., Chapelin, F. F., Liu, A. n., Rashidi, A. n., Soto, F. n., Quintana, Y. n., Davidzon, G. A., Marycz, K. n., Gibbs, I. C., Chonde, D. B., Patel, C. B., Daldrup-Link, H. E. 2021

  Abstract

  This paper summarizes the 2020 Diversity in Radiology and Molecular Imaging: What We Need to Know Conference, a three-day virtual conference held September 9-11, 2020. The World Molecular Imaging Society (WMIS) and Stanford University jointly organized this event to provide a forum for WMIS members and affiliates worldwide to openly discuss issues pertaining to diversity in science, technology, engineering, and mathematics (STEM). The participants discussed three main conference themes, "racial diversity in STEM," "women in STEM," and "global health," which were discussed through seven plenary lectures, twelve scientific presentations, and nine roundtable discussions, respectively. Breakout sessions were designed to flip the classroom and seek input from attendees on important topics such as increasing the representation of underrepresented minority (URM) members and women in STEM, generating pipeline programs in the fields of molecular imaging, supporting existing URM and women members in their career pursuits, developing mechanisms to effectively address microaggressions, providing leadership opportunities for URM and women STEM members, improving global health research, and developing strategies to advance culturally competent healthcare.

  View details for DOI 10.1007/s11307-021-01610-3

  View details for PubMedID 33903986