NIR + Ultrasound Clot Detector: Feasibility & Development Roadmap

Why the Combination Makes Sense

Existing Proof of Concept (You Are Not Starting from Zero)

1. NIRS-IVUS Dual Catheter (Already Clinical)

2. NIR-II Photoacoustic Imaging (The Most Exciting Direction)

• Spatial resolution of ultrasound (deep penetration)
• Chemical contrast of NIR (high sensitivity to hemoglobin/fibrin)
• Can delineate thrombi in real time with fibrin-specific targeting

3. NIR Fluorescence + Viscosity Sensing (PMID 36653196)

4. NIR-Ultrasound Nanomotors for Dual-Mode Detection (2024)

Three Technical Approaches You Can Take

Approach A: Photoacoustic Imaging System (Recommended)

1. NIR laser pulse (700-1350 nm) irradiates tissue
2. Hemoglobin/fibrin absorbs light and thermally expands
3. Ultrasound transducer detects the resulting pressure wave
4. Image reconstruction gives you a map of optical absorbers at ultrasound-level depth

• Wavelength: 750 nm (deoxy-Hb peak) vs 850 nm (oxy-Hb peak) - ratio gives oxygenation
• NIR-II window (1000-1350 nm) gives deeper penetration with less background
• Transducer frequency: 5-15 MHz for superficial veins (DVT), 1-3 MHz for deeper vessels

Approach B: Side-by-Side NIRS + B-mode Ultrasound with Co-registration

• DVT detection in limb veins (superficial enough for NIR penetration)
• Lower-cost prototype development
• Non-invasive bedside tool

Approach C: Intravascular NIRS-IVUS (Catheter-Based)

Key Technical Challenges to Solve

Recommended Development Phases

• Build a phantom (blood-mimicking gel + thrombus analog made from pooled blood + thrombin)
• Validate NIR spectral signatures of clot vs normal blood vs vessel wall
• Confirm ultrasound B-mode visibility of the same phantom
• Test co-registration accuracy

• Fresh excised porcine veins with induced thrombus
• Compare NIR+UST output against histology (gold standard)
• Optimize wavelength selection and transducer frequency

• Porcine or rat DVT model
• Non-invasive probe over femoral or jugular vein
• Compare against Doppler ultrasound (current clinical standard)

• Handheld wand with integrated NIR fibers + ultrasound array
• Real-time software visualization (false-color NIR overlay on B-mode ultrasound)
• Target use case: bedside DVT screening, ICU monitoring, or ER triage

Visualization Design

• Base layer: Standard B-mode ultrasound (grayscale anatomy)
• Overlay layer: NIR spectral map in pseudocolor (e.g., red = high deoxyhemoglobin = fresh clot, blue = fibrin-dominant = organized clot)
• Doppler layer: Flow velocity to detect occlusion
• Output: Combined 3-channel composite image with clot probability score

Bottom Line

Part 1: Will It Really Work? (Honest Assessment)

What Will Definitely Work

• Ultrasound alone already works for DVT - it is the current clinical gold standard (compression duplex ultrasound). Your UST component is proven.
• NIR spectroscopy can distinguish fresh clot (rich in deoxyhemoglobin, strong NIR absorption at 760 nm) from organized/fibrin-dominant old clot (different spectral signature). This is real science.
• The combination (photoacoustic mode) - where NIR light excites tissue and ultrasound picks up the acoustic signal - has been demonstrated in peer-reviewed research for thrombus imaging. It is not speculation.

What is Genuinely Hard

• NIR penetration through whole blood is limited to ~5-10 mm. For deep veins (iliac, femoral), pure NIR reflectance will not reach. Photoacoustic mode significantly extends this.
• Superficial veins (arm, calf, popliteal) are well within NIR range. For deep pelvic vessels, you will rely more on UST than NIR.
• Clot age discrimination needs multiple wavelengths (at least 3-5), not just one NIR source.
• Regulatory path is long - FDA 510(k) or PMA will be required.

Bottom Line

Part 2: Presentation Content for Medical/Clinical Panel

SLIDE 1 - TITLE

DualSense Clot Detector: A Combined Near-Infrared Spectroscopy and Ultrasound System for Real-Time Thrombus Detection and Characterization

Non-invasive, bedside visualization of blood clots using bimodal optical-acoustic imaging

SLIDE 2 - THE PROBLEM STATEMENT

• Venous thromboembolism (VTE) - DVT + pulmonary embolism - affects 200,000+ Americans annually
• PE is the 3rd most common cause of in-hospital death
• Autopsy studies show PE was missed in up to 70% of cases before death (Medscape/CDC, 2024)
• Venous thromboembolism is one of the top 5 conditions responsible for 39% of all serious misdiagnosis-related harm in US hospitals
• An estimated 795,000 Americans die or are permanently disabled each year from misdiagnosis - VTE is a major contributor

Current standard of care (compression duplex ultrasound) detects the location of a clot but tells us almost nothing about its composition, age, or instability - the very factors that determine treatment urgency and embolism risk.

1. No bedside tool can tell if a clot is fresh (high embolism risk) vs old/organized (lower risk)
2. Doppler ultrasound misses up to 30% of isolated calf DVTs
3. D-dimer blood tests are non-specific - high false-positive rate leading to unnecessary CT-PA scans with radiation exposure
4. ICU patients on bedrest: DVT incidence 29-33%, often silent and undetected until embolism

SLIDE 3 - WHY CURRENT TOOLS ARE NOT ENOUGH

SLIDE 4 - OUR SOLUTION

A handheld, non-invasive probe that combines Near-Infrared Spectroscopy with Ultrasound imaging to detect, locate, and characterize blood clots in real time at the bedside.

1. LOCATE - Ultrasound B-mode identifies vessel anatomy and confirms clot presence by loss of compressibility
2. CHARACTERIZE - NIR light (750-1000 nm) interrogates clot biochemistry: oxyhemoglobin vs deoxyhemoglobin ratio, fibrin density, lipid content
3. VISUALIZE - Software merges both signals into a single false-color overlay: clot location (UST) + clot composition map (NIR) displayed simultaneously on screen

• Is this clot fresh or old? (treatment urgency)
• Is it fibrin-stable or red-cell-rich? (thrombolysis suitability)
• Is the clot growing? (serial monitoring)

SLIDE 5 - THE SCIENCE BEHIND IT

• Deoxyhemoglobin (fresh clot) has a strong absorption peak at 760 nm
• Oxyhemoglobin absorbs at 850 nm
• Fibrin-dominant (old, organized) clots have a distinct spectral profile at 900-1000 nm
• Multi-wavelength NIR can "fingerprint" clot type the same way pulse oximetry reads blood oxygen

• Already clinical standard for DVT - compression ultrasound sensitivity ~95% for proximal DVT
• B-mode + Doppler gives anatomy + flow

• NIR laser pulse → absorbed by hemoglobin/fibrin → thermal expansion → ultrasound wave generated → detected by the same transducer
• This is photoacoustic imaging - NIR contrast with ultrasound depth. Published in peer-reviewed literature for thrombus detection (PMC10613240, 2023)

• NIRS-IVUS dual catheter already FDA-approved for coronary plaque (TVC Imaging System, InfraReDx)
• NIR fluorescence probes have demonstrated real-time navigation of venous thrombus in animal models (Zhang et al., Analytical Chemistry, 2023)
• NIR-II + ultrasound nanoprobes showed dual-mode thrombus detection AND thrombolysis in 2024 (Wang et al., J Nanobiotechnol)

SLIDE 6 - TARGET USE CASES

1. Emergency Department - Rapid bedside DVT rule-in/rule-out without waiting for radiology; reduces unnecessary CT-PA
2. ICU Monitoring - Daily screening of bedbound patients; serial clot monitoring without transport
3. Post-surgical wards - Hip/knee replacement, major abdominal surgery patients (DVT incidence 48% without prophylaxis)
4. Oncology - Cancer patients have 4-7x higher VTE risk; frequent monitoring without repeated lab draws
5. Remote/point-of-care settings - Portable enough for ambulance, rural clinic, or military field use

SLIDE 7 - TECHNICAL LIMITATIONS & HOW WE ADDRESS THEM

SLIDE 8 - DEVELOPMENT ROADMAP

• Phase 1 (0-12 months): Bench prototype - NIR fiber array + commercial ultrasound transducer + tissue phantom validation
• Phase 2 (12-24 months): Ex vivo porcine vessel model - compare against histology; optimize wavelength selection
• Phase 3 (24-36 months): First-in-human pilot (n=30) - compare against duplex ultrasound + CT-PA in DVT-suspected patients
• Phase 4 (36-54 months): Multicenter clinical trial; FDA 510(k) submission
• Phase 5: Commercialization as handheld bedside device

SLIDE 9 - SUMMARY

Blood clots kill when they are missed or mischaracterized. Current tools show where a clot is. DualSense shows where it is, what it is made of, and how dangerous it is - non-invasively, at the bedside, in real time.

1. The science is proven - NIR spectroscopy and ultrasound both have decades of clinical use; the integration is novel
2. The clinical need is real - VTE is one of the most harmful and commonly missed diagnoses in hospital medicine
3. The technology is ready - photoacoustic imaging of thrombus has been demonstrated in peer-reviewed literature

Tips for Presenting to a Medical/Clinical Panel

• Lead with patient harm data - clinicians respond to mortality numbers and missed diagnosis rates more than engineering specs
• Acknowledge what ultrasound already does well - do not oversell by dismissing the standard of care; position this as an add-on capability
• Show you know the regulatory path - a clinical panel will ask "how do you get this approved?" Have a 510(k) answer ready
• Address false-positive risk directly - any new diagnostic tool must prove it does not increase unnecessary anticoagulation (bleeding risk)
• Use the phrase "clot characterization" - this is what clinicians will immediately understand as the gap you are filling