About

Raag Airan is an Associate Professor of Radiology (Neuroimaging and Neurointervention) and, by courtesy, of Materials Science & Engineering and of Psychiatry and Behavioral Sciences at Stanford University. His research focuses on neuroimaging and neurointervention, integrating materials science and engineering principles with radiology to advance understanding and treatment of neurological conditions. His interdisciplinary role bridges the fields of materials science, engineering, and medical imaging, contributing to innovative approaches in neurotechnology and neurotherapeutics.

Research topics

• Medicine
• Radiology
• Computer Science
• Internal medicine
• Neuroscience
• Psychology
• Pharmacology
• Business
• Nanotechnology
• Cardiology
• Materials science
• Pathology
• Finance
• Biomedical engineering
• Chemistry

Selected publications

• Ethological profiling defines pain behaviors and parses analgesia from drug side effects in a mouse model of complex regional pain syndrome

  Pain · 2026-05-05 · 1 citations

  articleOpen access

  ABSTRACT: Complex regional pain syndrome (CRPS) is a form of chronic postinjury pain affecting the extremities with contributions from the somatic and sympathetic nervous systems. The mouse tibial fracture-cast model was developed to enable preclinical study of CRPS mechanisms and guide condition-specific drug development. Given the inherent limitations of reflex pain measures in mice, we sought to holistically characterize pain-like behaviors in this model in neutral and aversive environments using quantitative behavior analysis with LabGym, a user-friendly automation tool that requires no special equipment or extensive computational resources. This study shows that tibial fracture-cast injury causes distinct changes in naturalistic and nocifensive behaviors in male and female mice in neutral and aversive environments, demonstrating reliable behavioral categorization using robust learning-based holistic assessment. As proof-of-concept for therapeutic testing, we leveraged this behavioral evaluation to characterize the peripheral vs central effects of targeting alpha-2 receptors (α2-AR) with dexmedetomidine (DEX), a selective α2-AR agonist with analgesic, sedative, and anxiolytic properties. We found that DEX reduced mechanical allodynia primarily through central α2-ARs. Dexmedetomidine also decreased motion metrics, grooming, and rearing in an open field and distinctly affected the quality and quantity of grooming in an aversive environment, and systemic α2-AR antagonists did not suppress this effect. Importantly, we also determined that the sedative effects of DEX were attenuated in injured compared with uninjured mice, consistent with known sympathetic nervous system activation in CRPS. Overall, this study highlights the use of automated behavioral testing to parse analgesia from sedation in a unique preclinical pain model.

  PublisherDOI

• Is Ketamine an Opioid?

  Biological Psychiatry · 2026-01-14

  articleSenior author
  PublisherDOI

• Profiling the effects of subanesthetic ketamine on naturalistic behavior and brain microstructure

  Stanford Digital Repository · 2026-03-13

  dissertationOpen access
  PublisherDOI

• Abstract DP346: From Microstructure to Molecules: Mechanisms of Stem Cell–Driven White Matter Repair After Chronic Stroke

  Stroke · 2026-01-29

  article

  Introduction: Intraparenchymal transplantation of human neural stem cells (hNSCs) has shown safety and evidence of clinical efficacy in early chronic stroke trials, affecting distributed brain networks beyond the graft site. White matter, essential for communication within these networks, is profoundly disrupted after stroke, yet the spatiotemporal effects of transplanted hNSCs on its microstructural and cellular repair remain unknown. Here, we combined longitudinal diffusion MRI (dMRI) with high-resolution spatial transcriptomics to define mechanisms of hNSC-driven white matter repair. Methods: Adult male Sprague Dawley rats were subjected to 30 min of transient middle cerebral artery occlusion (MCAo) followed 1 month later by ipsilesional striatal injection (Tx) of embryonic-derived hNSCs (NR1) or vehicle. Rats underwent MRI (T2w, FLAIR, DWI, DTI) on a 7T Bruker BioSpec and a battery of neurobehavior tests over a 4-month post-stroke period. dMRI was processed via an atlas-registered pipeline for unbiased ROI- and voxel-wise analyses. 10X Genomics Xenium in situ transcriptomics was performed on coronal brain slices at Tx-site at 1 day and 3 months post-Tx. Results: NR1-treated rats exhibited significantly greater functional recovery than vehicle (p < 0.01). Stroke produced bilateral reductions in fractional anisotropy (FA) and quantitative anisotropy (QA) across major white-matter tracts including corpus callosum (CC) that were partially reversed by NR1; early dMRI changes (1–7 days) predicted long-term outcomes. In CC, NR1 accelerated oligodendrocyte lineage maturation and initiation of myelination (Sox10, Olig2, Enpp6, Bcas1, Plp1, Mag) with enrichment of axon ensheathment and lipid biosynthesis at 1 day. By 3 months, the NR1 group exhibited a mature myelin and compaction signatures (Plp1, Mag, Tspan2, Cryab, Klk6), whereas vehicle animals displayed higher chronic stress signaling (inflammasome, ER/UPR, oxidative/mitochondrial) and comparatively weaker structural myelin gene expression. Cell-state profiling indicated persistent glial activation in both groups, with vehicle skewed toward astrocyte/microglial stress and NR1 favoring immunoregulatory microglia and myelin-supportive signaling. Conclusion: NR1 transplantation drives coordinated microstructural recovery and oligodendrocyte-mediated remyelination of white matter after chronic stroke, linking early dMRI signatures to durable pro-myelinating transcriptional programs.

  PublisherDOI

• Abstract WP381: Spatiotemporal imaging and molecular signatures of stem cell transplant-driven recovery in stroke-injured brains

  Stroke · 2025-01-30

  article

  Introduction: Intraparenchymal transplantation (tx) of human neural stem cells is in clinical trial for chronic ischemic stroke, but the mechanisms of action are unknown. Here we use longitudinal MR imaging and spatial transcriptomics in a rodent stroke model to investigate the regenerative responses of cell therapy on regional and molecular levels. Methods: Adult male Sprague Dawley rats were subjected to 30 min of stroke (tMCAo) followed 1 month later by transplantation of embryonic-derived neural stem cells (NR1) or buffer into the ipsilesional striatum. We combined longitudinal MRI scans (T2w, FLAIR, DWI, SWI, DTI) with neurobehavior (whisker paw test, cylinder test, EBST, corner turn test, T-maze) and spatiotemporal transcriptomics. Results: NR1 transplantation significantly improved motor, sensorimotor and cognitive performance compared to the vehicle group (p<0.01). Most NR1-treated rats (94%) exhibited a new cortical T2-FLAIR signal, associated with positive outcomes, compared to 33% in the vehicle group. Additionally, the NR1-induced FLAIR signal was more hyperintense and persisted longer than in the vehicle group. Unbiased spatial transcriptomics of the cortical FLAIR region revealed a microglia/inflammation-associated signature including pathways involved in phagocytosis, immune cell response, cytokine signaling, and ER stress. DTI analysis of corticospinal, corticostriatal, nigrostriatal, spinothalamic, and callosal interhemispheric pathways showed that quantitative anisotropy (QA) values in the vehicle group remained stable from pre-transplant to 3 months post-transplant. In contrast, NR1-treated rats had higher pre-transplant QA values, which dropped below vehicle levels by day 7 post-transplant, but then significantly increased by 3 months, exceeding pre-transplant levels. This suggests substantial white matter recovery and fiber tract regeneration in the NR1-treated rats. Conclusion: Our study demonstrates T2-FLAIR may be a potential prognostic marker following stem cell transplantation, with further molecular analysis needed to deepen our understanding of brain restoration. Monitoring pre-transplant and early post-intervention QA values may enable patient selection and predict both early and long-term responses to cell therapy.

  PublisherDOI

• Developing algorithmic psychiatry via multi-level spanning computational models

  Cell Reports Medicine · 2025-04-28 · 3 citations

  reviewOpen access

  Modern psychiatry faces challenges in translating neurobiological insights into treatments for severe illnesses. The mid-20th century witnessed the rise of molecular mechanisms as pathophysiological and treatment models, with recent holistic proposals keeping this focus unaltered. In this perspective, we explore how psychiatry can utilize systems neuroscience to develop a vertically integrated understanding of brain function to inform treatment. Using schizophrenia as a case study, we discuss scale-related challenges faced by researchers studying molecules, circuits, networks, and cognition and clinicians operating within existing frameworks. We emphasize computation as a bridging language, with algorithmic models like hierarchical predictive processing offering explanatory potential for targeted interventions. Developing such models will not only facilitate new interventions but also optimize combining existing treatments by predicting their multi-level effects. We conclude with the prognosis that the future is bright, but that continued investment in research closely driven by clinical realities will be critical.

  PublisherDOI

• Cross-species quantification of the effect of ketamine on gray matter microstructure in obsessive-compulsive disorder

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  articleSenior author

  Motivation: Obsessive-compulsive disorder (OCD) is a chronic illness which may involve aberrant gray matter morphology. Ketamine, a rapid-acting antidepressant which induces structural neuroplasticity, decreases OCD symptoms. Therefore, gray matter microstructure could give insights and biomarkers for OCD symptom reduction. Goal(s): To characterize microstructure in OCD and how ketamine modulates it. Approach: Diffusion tensor and neurite orientation density and dispersion imaging were assessed in human OCD patients and OCD model mice before and after ketamine. Results: OCD patients and model mice show altered microstructure within cortico-striato-thalamo-cortical circuitry, primarily concentrated in subcortex for mice and cortex for humans. Ketamine-treated OCD model mice show increased neurite density. Impact: Gold standard approaches for preclinically quantifying drug-induced structural neuroplasticity involve histology and therefore cannot be applied for clinical purposes. We investigated across species whether gray matter microstructure quantification could bridge this gap in the context of ketamine's rapid anti-obsessional effects.

  PublisherDOI

• Combination of Neuronavigation-Guided Focused Ultrasound and Bevacizumab for Patients With Recurrent Glioblastoma: A Pilot Study

  Neurosurgery · 2025-11-24 · 1 citations

  articleOpen access

  BACKGROUND AND OBJECTIVES: Combining focused ultrasound (FUS)-induced blood-brain barrier opening with bevacizumab (BEV) has demonstrated survival benefits in preclinical models. This study aimed to evaluate the safety and feasibility of repeated FUS-BEV treatments in patients with recurrent glioblastoma and to explore imaging and serum biomarkers in relation to disease status. METHODS: This was a prospective, single-arm, open-label pilot trial. The primary end point was 6-month progression-free survival (PFS). Disease progression was assessed according to the Response Assessment in Neuro-Oncology criteria by independent radiological review. Radiological response was evaluated using fluid-attenuated inversion-recovery sequences to compare FUS-exposed vs nonexposed regions. Plasma cell-free DNA (cfDNA) concentrations were measured before and after FUS treatment. RESULTS: Between July 2020 and August 2023, 6 patients received a median of 14.5 sessions of biweekly FUS-BEV (10 mg/kg). The median PFS was 11 months, with a 6-month PFS rate of 66.7%. The only FUS-related adverse event was transient scalp heating (grade 1; 1.9%). A fluid-attenuated inversion recovery normalization effect emerged within 1 month after treatment. Plasma cfDNA increased significantly post-FUS, with total cfDNA rising 2.03 ± 0.76-fold, EGFR cfDNA 1.77 ± 0.76-fold, and HMBS cfDNA 1.68 ± 0.66-fold. CONCLUSION: Repeated FUS-BEV treatment is safe and feasible in patients with recurrent glioblastoma. Randomized controlled trials are warranted to confirm its therapeutic efficacy and validate imaging and liquid biopsy biomarkers.

  PublisherDOI

• Ethological profiling of pain and analgesia in a mouse model of complex regional pain syndrome

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-01

  preprint

  ABSTRACT Complex regional pain syndrome (CRPS) is a form of chronic post-injury pain affecting the extremities. The mouse tibial fracture- cast model was developed to enable preclinical study of CRPS mechanisms and guide condition-specific drug development. Given the inherent limitations of reflex pain measures in mice, we sought to characterize pain-like behaviors in this model more holistically. We evaluated spontaneous and evoked pain and naturalistic behaviors after tibial fracture-cast injury in male mice in neutral and aversive environments using LabGym. Here, we report a unique ethological signature of pain in injured mice characterized by reflexive allodynia, thermal hyperalgesia, frequent grooming and reduced rearing in neutral and aversive environments, and decreased paw withdrawal and increased paw licking in an aversive environment. As proof-of-concept, we also leveraged this holistic behavioral evaluation for drug screening by characterizing the peripheral versus central effects of targeting alpha-2 receptors (α2-AR) in the tibial fracture-cast model. We evaluated the impact of systemic delivery of dexmedetomidine (DEX), a selective α2-AR agonist, with or without antagonists, on holistic behavioral metrics in injured male mice. We found that DEX reduced mechanical allodynia primarily via central α2-ARs. DEX also decreased motion metrics, grooming and rearing in an open field, and distinctly affected the quality and quantity of grooming in an aversive environment, and this effect was not suppressed by systemic α2-AR antagonists. Ultimately, this study holistically captures pain-related behaviors and provides a detailed characterization of the relative contributions of peripheral and central α2-ARs to alpha2-mediated analgesia in male mice after tibial fracture-cast injury.

  PublisherDOI

• Ketamine-induced static and dynamic functional connectivity changes are modulated by opioid receptors and biological sex in rats

  Neuropsychopharmacology · 2025-04-19 · 3 citations

  articleOpen access

  Subanesthetic ketamine is currently used as a rapid-acting treatment for varied neuropsychiatric disorders. However, the mechanistic underpinnings of its therapeutic action remain unclear, and emerging clinical and preclinical evidence highlights a potential involvement of the opioid system. We used pharmacological functional ultrasound imaging data acquired during and after ketamine administration in male and female rats pretreated with naltrexone, an opioid receptor antagonist, or vehicle. We found that ketamine-induced functional connectivity changes are modulated by opioid receptor blockade, and that these responses are dependent on biological sex. Specifically, naltrexone sex-dependently altered the connectivity patterns within the medial prefrontal cortex (mPFC), a key node of the brain's default-mode network, and between the mPFC and other functional nodes. Furthermore, ketamine produced an opioid-dependent shift toward states of increased dysconnectivity and brain entropy in male rats only. Our findings warrant further investigation into the neurophysiological underpinnings of ketamine action and potential sex-specific interactions with opioid receptors.

  PublisherOA PDFDOI

Recent grants

• NIH Grant RF1MH114252

  NIH · $1.6M · 2022

Frequent coauthors

• Peter C.M. van Zijl

  Johns Hopkins University

  25 shared

• Jay J. Pillai

  Mayo Clinic

  24 shared

• Haris I. Sair

  Johns Hopkins University

  23 shared

• Kim Butts Pauly

  21 shared

• Keyvan Farahani

  National Heart Lung and Blood Institute

  19 shared

• Vera A. Khokhlova

  Lomonosov Moscow State University

  18 shared

• Ari Partanen

  Profound Medical (Canada)

  18 shared

• Jeff W. M. Bulte

  Johns Hopkins Medicine

  16 shared

Education

• Ph.D., Materials Science and Engineering

  Stanford University

  2007

• M.S., Materials Science and Engineering

  Stanford University

  2003

• B.S., Materials Science and Engineering

  Stanford University

  2001