Choosing a laser for laser speckle contrast imaging

The use of laser speckle contrast imaging (LSCI) has expanded rapidly for characterizing the motion of scattering particles. Speckle contrast is related to the dynamics of the scattering particles via a temporal autocorrelation function, but the quality of various elements of the imaging system can adversely affect the quality of the signal recorded by LSCI. While it is known that the laser coherence affects the speckle contrast, it is generally neglected in in vivo LSCI studies and was not thoroughly addressed in a practical matter. In this work, we address the question of how the spectral width of the light source affects the speckle contrast both experimentally and through numerical simulations. We show that commonly used semiconductor laser diodes have a larger than desired spectral width that results in a significantly reduced speckle contrast compared with ideal narrow band lasers. This results in a reduced signal-to-noise ratio for estimating changes in the motion of scattering particles. We suggest using a volume holographic grating stabilized laser diode or other diodes that have a spectrum of emitted light narrower than ≈1 nm to improve the speckle contrast.D.D. Postnov was supported by grant NNF17OC0025224 awarded by Novo Nordisk Foundation, Denmark. Support was also provided by NIH R01-MH111359, R01-EB021018, and R01-NS108472. (NNF17OC0025224 - Novo Nordisk Foundation, Denmark; R01-MH111359 - NIH; R01-EB021018 - NIH; R01-NS108472 - NIH)https://www.nature.com/articles/s41598-019-39137-xPublished versionPublished versio

Awake chronic mouse model of targeted pial vessel occlusion via photothrombosis

Animal models of stroke are used extensively to study the mechanisms involved in the acute and chronic phases of recovery following stroke. A translatable animal model that closely mimics the mechanisms of a human stroke is essential in understanding recovery processes as well as developing therapies that improve functional outcomes. We describe a photothrombosis stroke model that is capable of targeting a single distal pial branch of the middle cerebral artery with minimal damage to the surrounding parenchyma in awake head-fixed mice. Mice are implanted with chronic cranial windows above one hemisphere of the brain that allow optical access to study recovery mechanisms for over a month following occlusion. Additionally, we study the effect of laser spot size used for occlusion and demonstrate that a spot size with small axial and lateral resolution has the advantage of minimizing unwanted photodamage while still monitoring macroscopic changes to cerebral blood flow during photothrombosis. We show that temporally guiding illumination using real-time feedback of blood flow dynamics also minimized unwanted photodamage to the vascular network. Finally, through quantifiable behavior deficits and chronic imaging we show that this model can be used to study recovery mechanisms or the effects of therapeutics longitudinally.R01 EB021018 - NIBIB NIH HHS; R01 MH111359 - NIMH NIH HHS; R01 NS108472 - NINDS NIH HHSPublished versio

MATLAB code and data processing guide for phase resolved Doppler Optical Coherence Tomography

Example data is available through: https://drive.google.com/open?id=168HD4lKt0K97g09zus6H9h7lAyO0jOBZ https://drive.google.com/open?id=1QvTO_41cPN3_wM9wxCh9NECv_hypVZPCThis guide and the MATLAB code are for post data processing of prDOCT, which outputs 3D vascular blood flow velocity

Capillary red blood cell velocimetry by phase-resolved optical coherence tomography

https://www.spiedigitallibrary.org/conference-proceedings-of-spie/10483/2290655/Capillary-red-blood-cell-velocimetry-by-phase-resolved-optical-coherence/10.1117/12.2290655.full?SSO=1Published versio

MATLAB code and data processing guide for Optical Coherence Tomography Angiography

Example data is available through: https://drive.google.com/a/bu.edu/file/d/1q9_F93_5p_pgmXIwzKZOCQ36m7sE95d2/view?usp=sharing https://drive.google.com/a/bu.edu/file/d/1nNzjBI2JZFf4epRr4XSKhRYiT7FJcZT7/view?usp=sharing https://drive.google.com/a/bu.edu/file/d/1dAwY56dSBoRLX246ALTeV3ZiV3dehrEH/view?usp=sharing https://drive.google.com/a/bu.edu/file/d/1TUA9L170blYQdrI6L9oiSkxae7XpV--E/view?usp=sharing https://drive.google.com/a/bu.edu/file/d/1J3gG6HFBK2uVjDgCRHbRV6fvA2Ei9YHp/view?usp=sharingThis guide is for post data processing of OCTA which outputs the vascular structure

Capillary red blood cell velocimetry by phase-resolved optical coherence tomography

We present a phase-resolved optical coherence tomography (OCT) method to extend Doppler OCT for the accurate measurement of the red blood cell (RBC) velocity in cerebral capillaries. OCT data were acquired with an M-mode scanning strategy (repeated A-scans) to account for the single-file passage of RBCs in a capillary, which were then high-pass filtered to remove the stationary component of the signal to ensure an accurate measurement of phase shift of flowing RBCs. The angular frequency of the signal from flowing RBCs was then quantified from the dynamic component of the signal and used to calculate the axial speed of flowing RBCs in capillaries. We validated our measurement by RBC passage velocimetry using the signal magnitude of the same OCT time series data.National Institutes of Health (NIH) (1S10RR023043, P01-NS055104, P41-EB015896, R01-EB021018, R01MH111359); Air Force Office of Scientific Research (AFOSR) (FA-9550-15-1-0473). (1S10RR023043 - National Institutes of Health (NIH); P01-NS055104 - National Institutes of Health (NIH); P41-EB015896 - National Institutes of Health (NIH); R01-EB021018 - National Institutes of Health (NIH); R01MH111359 - National Institutes of Health (NIH); FA-9550-15-1-0473 - Air Force Office of Scientific Research (AFOSR))https://www.osapublishing.org/ol/abstract.cfm?uri=ol-42-19-3976https://www.osapublishing.org/ol/abstract.cfm?uri=ol-42-19-3976Published versio

Cardiac pulsatility mapping and vessel type identification using laser speckle contrast imaging

Systemic flow variations caused by the cardiac cycle can play a role or be an important marker in both normal and pathological conditions. The shape, magnitude and propagation speed of the flow pulse reflect mechanical properties of the vasculature and are known to vary significantly with vascular diseases. Most conventional techniques are not capable of imaging cardiac activity in the microcirculation due to spatial and/or temporal resolution limitations and instead make inferences about propagation speed by making measurements at two points along an artery. Here, we apply laser speckle contrast imaging to images with high spatial resolution in the high frequency harmonics of cardiac activity in the cerebral cortex of a mouse. We reveal vessel dependent variation in the cardiac pulse activity and use this information to automatically identify arteries and veins.Novo Nordisk Foundation, Denmark (NNF17OC0025224); National Institutes of Health (NIH) (R01-MH111359, R01-EB021018, and R01-NS108472). (NNF17OC0025224 - Novo Nordisk Foundation, Denmark; R01-MH111359 - National Institutes of Health (NIH); R01-EB021018 - National Institutes of Health (NIH); R01-NS108472 - National Institutes of Health (NIH))https://www.osapublishing.org/boe/abstract.cfm?uri=boe-9-12-6388Published versio

Paradoxical Air Microembolism Induces Cerebral Bioelectrical Abnormalities And Occasionally Headache In Patent Foramen Ovale Patients With Migraine

Background Although controversial, paradoxical embolism via patent foramen ovale (PFO) may account for some of the migraine attacks in a subset of migraine with aura (MA) patients. Induction of MA attacks with air bubble injection during transcranial Doppler ultrasound in MA patients with PFO supports this view. It is likely that cerebral embolism in patients with right-to-left shunt induces bioelectrical abnormalities to initiate MA under some conditions. Methods and Results We investigated changes in cerebral bioelectrical activity after intravenous microbubble injection in 10 MA patients with large PFO and right-to-left cardiac shunt. Eight PFO patients without migraine but with large right-to-left shunt and 12 MA patients without PFO served as controls. Four MA patients with PFO were reexamined with sham injections of saline without microbubbles. Bioelectrical activity was evaluated using spectral electroencephalography and, passage of microbubbles through cerebral arteries was monitored with transcranial Doppler ultrasound. Microbubble embolism caused significant electroencephalographic power increase in MA+PFO patients but not in control groups including the sham-injected MA+PFO patients. Headache developed in 2 MA with PFO patients after microbubble injection. Conclusions These findings demonstrate that air microembolism through large PFOs may cause cerebral bioelectrical disturbances and, occasionally, headache in MA patients, which may reflect an increased reactivity of their brain to transient subclinical hypoxia–ischemia, and suggest that paradoxical embolism is not a common cause of migraine but may induce headache in the presence of a large PFO and facilitating conditions.PubMedWoSScopu

Choosing a model for laser speckle contrast

Laser speckle contrast imaging (LSCI) is a real-time full-field non-invasive technique, which is broadly applied to visualize blood flow in biomedical applications. In its foundation is the link between the speckle contrast and dynamics of light scattering particles–erythrocytes. The mathematical form describing this relationship, which is critical for accurate blood flow estimation, depends on the sample’s light-scattering properties. However, in biological applications, these properties are often unknown, thus requiring assumptions to be made to perform LSCI analysis. Here, we review the most critical assumptions in the LSCI theory and simulate how they affect blood flow estimation accuracy. We show that the most commonly applied model can severely underestimate the flow change, particularly when imaging brain parenchyma or other capillary perfused tissue (e.g. skin) under ischemic conditions. Based on these observations and guided by the recent experimental results, we propose an alternative model that allows measuring blood flow changes with higher accuracy