Diffuse Correlation Spectroscopy Beyond the Water Peak Enabled by Cross-Correlation of the Signals From InGaAs/InP Single Photon Detectors.

OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique that allows for the non-invasive measurement of blood flow. Recent work has shown that utilizing longer wavelengths beyond the traditional NIR range provides a significant improvement to signal-to-noise ratio (SNR). However, current detectors both sensitive to longer wavelengths and suitable for clinical applications (InGaAs/InP SPADs) suffer from suboptimal afterpulsing and dark noise characteristics. To overcome these barriers, we introduce a cross correlation method to more accurately recover blood flow information using InGaAs/InP SPADs. METHODS: Two InGaAs/InP SPAD detectors were used for during in vitro and in vivo DCS measurements. Cross correlation of the photon streams from each detector was performed to calculate the correlation function. Detector operating parameters were varied to determine parameters which maximized measurement SNR.State-space modeling was performed to determine the detector characteristics at each operating point. RESULTS: Evaluation of detector characteristics was performed across the range of operating conditions. Modeling the effects of the detector noise on the correlation function provided a method to correct the distortion of the correlation curve, yielding accurate recovery of flow information as confirmed by a reference detector. CONCLUSION: Through a combination of cross-correlation of the signals from two detectors, model-based characterization of detector response, and optimization of detector operating parameters, the method allows for the accurate estimation of the true blood flow index. SIGNIFICANCE: This work presents a method by which DCS can be performed at longer NIR wavelengths with existing detector technology, taking advantage of the increased SNR.

Target-specific contrast agents for magnetic resonance microscopy.

High-resolution ex vivo magnetic resonance (MR) imaging can be used to delineate prominent architectonic features in the human brain, but increased contrast is required to visualize more subtle distinctions. To aid MR sensitivity to cell density and myelination, we have begun the development of target-specific paramagnetic contrast agents. This work details the first application of luxol fast blue (LFB), an optical stain for myelin, as a white matter-selective MR contrast agent for human ex vivo brain tissue. Formalin-fixed human visual cortex was imaged with an isotropic resolution between 80 and 150 microm at 4.7 and 14 T before and after en bloc staining with LFB. Longitudinal (R1) and transverse (R2) relaxation rates in LFB-stained tissue increased proportionally with myelination at both field strengths. Changes in R1 resulted in larger contrast-to-noise ratios (CNR), per unit time, on T1-weighted images between more myelinated cortical layers (IV-VI) and adjacent, superficial layers (I-III) at both field strengths. Specifically, CNR for LFB-treated samples increased by 229 +/- 13% at 4.7 T and 269 +/- 25% at 14 T when compared to controls. Also, additional cortical layers (IVca, IVd, and Va) were resolvable in 14 T-MR images of LFB-treated samples but not in control samples. After imaging, samples were sliced in 40-micron sections, mounted, and photographed. Both the macroscopic and microscopic distributions of LFB were found to mimic those of traditional histological preparations. Our results suggest target-specific contrast agents will enable more detailed MR images with applications in imaging pathological ex vivo samples and constructing better MR atlases from ex vivo brains.

Detection of entorhinal layer II using 7Tesla [corrected] magnetic resonance imaging.

The entorhinal cortex lies in the mediotemporal lobe and has major functional, structural, and clinical significance. The entorhinal cortex has a unique cytoarchitecture with large stellate neurons in layer II that form clusters. The entorhinal cortex receives vast sensory association input, and its major output arises from the layer II and III neurons that form the perforant pathway. Clinically, the neurons in layer II are affected with neurofibrillary tangles, one of the two pathological hallmarks of Alzheimer's disease. We describe detection of the entorhinal layer II islands using magnetic resonance imaging. We scanned human autopsied temporal lobe blocks in a 7T human scanner using a solenoid coil. In 70 and 100 microm isotropic data, the entorhinal islands were clearly visible throughout the anterior-posterior extent of entorhinal cortex. Layer II islands were prominent in both the magnetic resonance imaging and corresponding histological sections, showing similar size and shape in two types of data. Area borders and island location based on cytoarchitectural features in the mediotemporal lobe were robustly detected using the magnetic resonance images. Our ex vivo results could break ground for high-resolution in vivo scanning that could ultimately benefit early diagnosis and treatment of neurodegenerative disease.