Continuous, bedside monitoring of cerebral blood flow in patients at risk for neurovascular complications has the
potential to decrease morbidity and mortality. For example, perioperative stroke has been estimated to occur in
approximately 10% of patients undergoing high risk cardiovascular or brain surgeries. These patients are
commonly identified by their difficulty to awaken following anesthesia, but this sign is not specific and could be
due to lingering anesthesia. While measures of systemic physiology can be used to infer cerebral perfusion, a
technology that directly and continuously measures cerebral blood flow (CBF) is needed to properly manage
treatment. Diffuse Correlation Spectroscopy (DCS) is an established optical technique that enables continuous,
non-invasive, and direct measurements of CBF. The effectiveness of DCS in measuring CBF is hampered in
adults by to extracerebral contamination and limited depth sensitivity. This proposal seeks to extend the
usefulness of DCS through the development of a new technique, known as acousto-optic modulated,
interferometric diffuse correlation spectroscopy (AOM-iDCS) at 1064 nm, which will enhance CBF sensitivity and
reduce extracerebral contamination. First, we will show the utility of moving to 1064 nm as compared to traditional
NIRS wavelengths (680–850 nm), benefitting from both greater photon penetration depth as well as an increased
overall number of detected photons, ~15 to 20x. To overcome single photon detector shortcomings at 1064 nm,
we will utilize a heterodyne interferometric technique to enable coherent amplification of the speckle signal.
Second, we will develop acousto-optic modulated DCS to increase the sensitivity of blood flow measurements
to deeper flows. We will optimize the applied ultrasound pressure distribution to maximize sensitivity to CBF,
develop theoretical models for the extraction of blood flow from the modulated signal, and demonstrate increased
depth sensitivity and selectivity. Finally, we will combine the two techniques to demonstrate AOM-iDCS,
benefitting not only from the individual techniques’ strengths but also synergies between them. By modulating
the reference arm at the ultrasound frequency, the tagged light signal will be frequency demodulated, and the
untagged light will be shifted to the ultrasound frequency, which can then be removed by a low pass filter. The
proposed research represents a significant improvement in both sensitivity to CBF and rejection of extracerebral
contamination. We believe the successful completion of this research will lead to a device readily translatable to
the clinic for the management of patients in neuro-critical care. The proposed training plan gives opportunities to
develop technical skills, both in theoretical and hardware related matters through the development of AOM-iDCS;
scientific communication skills, through dissemination of the proposed research through written works as well as
presentations at conferences; professionally, through networking at conferences as well as utilizing the many
resources available through the sponsoring institutions (MGH, Harvard-MIT HST); and long term career skills,
through mentoring of research assistants and master students and participating in manuscript review.
