Affordable Shortwave Infrared Spectroscopy for Stroke Risk Screening in Children with Sickle Cell Disease

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PROJECT SUMMARY The risk of stroke in children with sickle cell disease (SCD) is enormous, ~300 times higher than healthy children without SCD and heart disease. Without treatment, ~11% of SCD patients have clinically apparent stroke by their age of 20 and the risk is the most significant between ages 2 and 5. For stroke prevention, early identification of abnormal cerebral perfusion is critical to initiating a timely therapeutic intervention. The current standard screening tool is a transcranial ultrasound doppler (TCD). In high-resource settings, the TCD screening followed by blood transfusion therapy has reduced the risk of stroke by 92%. Unfortunately, TCD screening is not widely available due to a high cost and a lack of trained personnel in low resource settings such as sub-Saharan Africa where most sickle cell patients live. Here we propose to engineer an affordable non-invasive optical technique that can quantify microvascular cerebral blood flow (CBF) in pediatric sickle cell disease. Specifically, we will build a speckle contrast optical spectroscopy (SCOS) system working in the shortwave infrared (SWIR or 2nd near-infrared, NIR) region for the enhanced depth sensitivity with ×10 higher SNR at a lower cost (×10 less) compared to the current NIR system. First, we will computationally investigate the high depth-sensitivity of SWIR SCOS using a multi-layer Monte Carlo simulation on a realistic head model. We will also perform experimental verification using a benchtop SWIR SCOS system comprising a SWIR long-coherence laser and an off-the-shelf InGaAs camera. The benchmark tests will be performed against NIR SCOS to characterize SNR, depth sensitivity and accuracy on fabricated microfluidic channels mimicking layered microvascular networks. Next, we will explore the feasibility of a portable SWIR SCOS system using a low-cost Germanium-based SWIR camera and validate the developed protype by measuring CBF of healthy adults undergoing a hypercapnic challenge. The scientific goal of this proposal is to study the SWIR range for SCOS enabling assessment of deeper tissue microvascular blood flow. The SWIR optical transmission window has several advantages over the NIR range (700-900nm) including lower tissue optical attenuation, more photon numbers per unit energy and higher maximum permissible exposure to skin. With these benefits, SWIR has been explored in many optical imaging and spectroscopic techniques including fluorescence or photoacoustic imaging, and diffuse reflectance spectroscopies but not yet in SCOS. The higher depth-sensitivity will mitigate signal contamination from the extracerebral layers (i.e. skull/scalp), contributing to more accurate estimation of cerebral blood flow. The proposed research will create a prototype of a portable deep tissue flowmeter ready for a clinical pilot study in children with sickle cell disease. In the long-term, this device may address the paucity of neuroimaging modalities in the low-resource settings.