Research

New Modalities. New Physics. Built on the same chip lines making our phones. 

The Evidence

Near-infrared light has long been used in functional imaging — fNIRS systems measure how much light is absorbed by tissue to infer oxygen levels and blood flow. Openwater goes deeper. By recording the phase of coherent laser light — not just its intensity — we capture how light waves interfere after passing through tissue, revealing hemodynamic detail that absorption measurements alone cannot see: real-time blood flow, blood volume, and micromotion at a resolution that conventional fNIRS cannot approach.³

Focused ultrasound is being studied for over 180 diseases worldwide — 34 regulatory approvals, over one million patients treated.² Early pooled results from human trials have shown response rates exceeding 75% for mental diseases.¹

These fields are not new. Focused ultrasound and functional near-infrared imaging have been active areas of research for decades. But the physics Openwater is working with — phase-coherent laser measurement of hemodynamics, low-intensity ultrasound precise enough to select specific cell types — represents a new class of capability, not an incremental improvement on what came before. We are not miniaturizing existing tools. We are making measurements and interventions that were not previously possible.

In Openwater's own published trial at the University of Arizona, 35% of participants with treatment-resistant depression reached full clinical remission — after less than two hours of total treatment time.⁵

Disease Areas

Brain & Mental Health  Depression, Alzheimer's, Parkinson's, TBI, stroke, addiction, anxiety — the evidence base spans hundreds of clinical trials across both near-infrared imaging and focused ultrasound. The brain responds to both modalities through distinct but complementary mechanisms: light through hemodynamic measurement and mapping; ultrasound through direct, reversible neuromodulation of specific circuits. Neither requires drugs. Neither causes lasting tissue damage at low intensity.

Cancer  Focused ultrasound is in active clinical trials for glioblastoma, pancreatic cancer, prostate cancer, liver tumors, and brain metastases. Precise hemodynamic imaging opens a parallel path — detecting the microvascular signatures of tumor activity and tracking treatment response in real time, without radiation.

Metabolic & Autoimmune Disease  Near-infrared hemodynamic imaging reveals the microvascular dysfunction that underlies many chronic metabolic and autoimmune conditions. Low-intensity focused ultrasound offers a path to modulating the cellular activity driving them — without drugs, without surgery, without side effects.

Long COVID  Emerging clinical work points to persistent microvascular and mitochondrial dysfunction as a root cause of long COVID symptoms. Both real-time hemodynamic measurement and targeted low-intensity ultrasound are active areas of investigation.

Veterinary  Canine arthritis has become an important validation target: animals cannot report placebo effects, making positive results in pain and mobility particularly meaningful. Results from ongoing studies are informing protocol development for human trials.

Openwater's Trials

We are running and supporting trials across several of these areas now — with customers including universities, government agencies, foundations, and individuals operating their own studies using Openwater hardware.⁶ Every trial adds to a shared dataset. Every result — positive or negative — makes the platform smarter.

Human studies have been conducted at Hartford Hospital, Brown University, University of Pennsylvania, University of Arizona, UCLA, University of Birmingham, MIT and other institutions since 2021.

Citations

¹ Tan G, Chen H, Leuthardt EC. "Ultrasound Applications in the Treatment of Major Depressive Disorder." Neuromodulation, 2025. Pooled LIFU response rate (≥50% improvement) across human trials: 77.36%. Preprint; peer review ongoing.

² Focused Ultrasound Foundation. "Focused Ultrasound Exceeds One Million Patients Treated Worldwide." 2025. fusfoundation.org. Includes 180+ diseases studied, 34 regulatory approvals, 1M+ patients treated.

³ Li J et al. "The Most Fundamental and Popular Literature on fNIRS: A Bibliometric Analysis." Frontiers in Neurology, 2024. Over 9,400 fNIRS publications identified as of 2023.

⁴ Open-Motion: Favilla CG, Carter S, Hartl B, Gitlevich R, Mullen MT, Yodh AG, Baker WB, Konecky S. Neurophotonics 11(1), 2024. DOI: 10.1117/1.NPh.11.1.015008. Favilla CG, Baird GL, Grama K, Konecky S et al. Journal of NeuroInterventional Surgery, 2024.

⁵ Open-LIFU: Bawiec CR, Hollender PJ, Ornellas SB, Konecky SD et al. Journal of Ultrasound in Medicine, Feb 2025. DOI: 10.1002/jum.16600. Schachtner JN, Dahill-Fuchel JF, Allen KE, Bawiec CR, Hollender PJ, Konecky SD, Allen JJB. Frontiers in Psychiatry 16, 2025. DOI: 10.3389/fpsyt.2025.1451828.

⁶ Human studies initiated under IRB approval at Hartford Hospital, 2021. Subsequent studies conducted at Brown University, University of Pennsylvania, University of Arizona, UCLA, and additional institutions. Data on file.

 

Some Examples

See further deep dives below and on our Community Page.  

 

Our early results show the promise of scaling to many diseases with significant cost savings & time advantages as a platform

 

Our highly reconfigurable open-source devices are poised to change the way medical devices are developed and deployed.

 

Publications

 

Regulatory Findings

 

Study Data

Rethinking Real-Time Bloodflow
Motion Webinar
Forbes Wearable Ultrasound
Open-LIFU Webinar
 
Accelerating Clinical Innovation

 

 

 

Neurology Live

Peer Reviewed Publications

Our Research Efforts To Date:
Device
Status
NPh-11-1-270
Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath-hold maneuver

We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from changes in speckle contrast, and relative blood volume (rBV) was derived from changes in speckle average intensity.
JNIFavilla
Portable cerebral blood flow monitor to detect large vessel occlusion in patients with suspected stroke
Background 

Early detection of large vessel occlusion (LVO) facilitates triage to an appropriate stroke center to reduce treatment times and improve outcomes. Prehospital stroke scales are not sufficiently sensitive, so we investigated the ability of the portable Openwater optical blood flow monitor to detect LVO.
jum.v44.2.cover
A Wearable, Steerable, Transcranial Low-Intensity Focused Ultrasound System
Objectives

Transcranial low-intensity focused ultrasound (LIFU) offers unique opportunities for precisely neuromodulating small and/or deep targets within the human brain, which may be useful for treating psychiatric and neurological disorders. This article presents a novel ultrasound system that delivers focused ultrasound through the forehead to anterior brain targets and evaluates its safety and usability in a volunteer study.
FIP1
Transcranial focused ultrasound targeting the default mode network for the treatment of depression
Introduction

Up to 50% of individuals fail to respond to current depression treatments. Repetitive negative thought and default mode network hyperconnectivity are central in depression and can potentially be targeted using novel neuromodulation techniques. This community-based study assessed whether a treatment using non-invasive transcranial focused ultrasound targeting the default mode network can decrease depression symptoms and repetitive negative thought, and improve quality of life.

 
FIBioengineering2
Low-intensity ultrasound lysis of amyloid microclots in a lab-on-chip model
Abstract

Amyloid fibrin(ogen) microclots are misfolded protein aggregates with β-sheet structures that have been associated with Long COVID and numerous thrombo-inflammatory diseases. These microclots persist in circulation and obstruct microvasculature, impair oxygen transport and promote chronic inflammation. Conventional thrombolytic therapies such as recombinant tissue plasminogen activator (rtPA) show limited efficacy against these microclots due to their structure and composition. In this study, we assess the impact of low intensity focused ultrasound (LIFU) stimulation on amyloid microclot fragmentation, the role of cavitation in this process and investigate whether microbubble-assisted ultrasound can enhance their lysis. 
biorxiv_article_logo
Detection of Long COVID Microclots using Pulsed Speckle Contrast Optical Spectroscopy
Abstract

Circulating microclots are increasingly linked to long COVID as well as its persistent symptoms such as fatigue, cognitive deficits, and cardiovascular complications. These conditions can become debilitating or even life-threatening, which create an urgent need for rapid and reliable detection and monitoring tools. In this study we investigate pulsed speckle contrast optical spectroscopy (p-SCOS) as a non-invasive and label-free method to detect microclots in biofluids. Microclots at four concentrations (21k, 91k, 400k, and 1.7M microclots/mL), representing levels from healthy individuals to acute coagulopathic states, were generated using a freeze-thaw method. We measured speckle contrast under flowing conditions in a custom-made flow phantom. In phosphate-buffered saline (PBS) and plasma, increasing microclot concentration consistently led to measurable decreases in speckle contrast. The measurement differentiated between low and high clot burdens in transparent media which highlights its potential for microclot monitoring. In comparison, no detectable changes were observed in whole blood, likely due to dominant scattering from red blood cells masking microclot effects. Overall, our findings demonstrate the feasibility of p-SCOS as a rapid and label-free tool for microclot detection and monitoring in transparent biofluids.
biorxiv_article_logo
Investigation of the Synergistic Effect of Enzymatic and Ultrasound-Induced Amyloid Microclot Degradation
Abstract

Amyloid microclots have been implicated in thrombotic complications across various pathological conditions such as Long COVID symptoms, yet their resistance to enzymatic fibrinolysis causes a therapeutic challenge. In this study we examine the effects of three fibrinolytic enzymes rtPA, Lumbrokinase, and Nattokinase on plasma-derived amyloid microclots, in combination with ultrasound-induced microstreaming and microbubbles. A lab-on-chip platform was used to expose the clots to ultrasound at 150, 300, and 500 kHz. Quantitative analysis revealed that ultrasound alone significantly disrupted clot structures, particularly at 150 kHz, where mean clot diameter was reduced by over 60% and large-clot count (>30 µm) dropped by more than 80% compared to controls. The addition of fibrinolytic enzymes, however, did not produce statistically significant effects at 150 or 300 kHz which indicates that mechanical forces were the dominant contributors to clot disruption. At 500 kHz, where ultrasound alone was less effective, enzymatic treatment moderately enhanced the reduction in large-clot burden. These results show the potential of low-frequency ultrasound as a primary method of amyloid microclot breakdown, with enzyme co-treatment offering limited but measurable effect.
Open-LIFU Webinar
Transcranial Focused Ultrasound Neuromodulation of the Default Mode Network in the Treatment of Depression and Promotion of Wellness
Webinar

In this webinar, Dr. John Allen introduces how low-intensity transcranial focused ultrasound (litFUS), a non-invasive, high-precision neuromodulation technique, has the potential to modulate Default Mode Network (DMN) activity.

 

 WATCH WEBINAR 
Motion Webinar
Clinical Applications of Optical Cerebral Blood Flow Imaging 
Webinar

Cerebral blood flow optimization is a pillar of clinical management of various neurological conditions. However, continuous non-invasive cerebral hemodynamic monitoring presents a significant challenge even in the most advanced health care settings. Here, we will discuss how biomedical optical imaging modalities are well positioned to address this unmet need. Recent studies will be leveraged to support the idea that optically-derived cerebral blood flow can (1) serve as a surrogate endpoint for early-phase trials aimed at hemodynamic optimization, (2) be used to quantify microvascular reperfusion in stroke, (3) detect large vessel occlusion, and (4) monitor patients at risk of hemodynamic failure. The overarching goal is to highlight the diversity of potential clinical applications to inspire cutting edge research that will ultimately improve the care we provide to patients with cerebrovascular disease.

WATCH WEBINAR