Venkaiah C. Kavuri

Noninvasive optical monitoring of critical closing pressure and arteriole compliance in human subjects

The critical closing pressure (CrCP) of the cerebral circulation depends on both tissue intracranial pressure and vasomotor tone. CrCP defines the arterial blood pressure (ABP) at which cerebral blood flow approaches zero, and their difference (ABP − CrCP) is an accurate estimate of cerebral perfusion pressure. Here we demonstrate a novel non-invasive technique for continuous monitoring of CrCP at the bedside. The methodology combines optical diffuse correlation spectroscopy (DCS) measurements of pulsatile cerebral blood flow in arterioles with concurrent ABP data during the cardiac cycle. Together, the two waveforms permit calculation of CrCP via the two-compartment Windkessel model for flow in the cerebral arterioles. Measurements of CrCP by optics (DCS) and transcranial Doppler ultrasound (TCD) were carried out in 18 healthy adults; they demonstrated good agreement (R = 0.66, slope = 1.14 ± 0.23) with means of 11.1 ± 5.0 and 13.0 ± 7.5 mmHg, respectively. Additionally, a potentially useful and rarely measured arteriole compliance parameter was derived from the phase difference between ABP and DCS arteriole blood flow waveforms. The measurements provide evidence that DCS signals originate predominantly from arteriole blood flow and are well suited for long-term continuous monitoring of CrCP and assessment of arteriole compliance in the clinic.

A Combined Diffuse Correlation and Time-Resolved Spectroscopy Instrument for Continuous monitoring of Absolute Cerebral Blood Flow

We investigate the feasibility of constructing an instrument, which can help critical care physicians by real-time monitoring/measuring absolute cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) to facilitate fast diagnosis of Ischemia.

Multimodal Structural Priors for Spatially-Dense Diffuse Optical Tomography of Breast Cancer

We demonstrate spatially-dense diffuse optical tomographic (DOT) reconstructions of breast cancer utilizing two forms of structural priors: MR images from a concurrent DOT-MRI instrument and fringe-projection profilometry in an optical-only system.

Multi-frequency diffuse optical tomography for cancer detection

Previous work has validated that the accuracy of absorption coefficient can be improved using frequency-domain (FD) DOT measurements with multiple modulation frequencies. In this paper, we investigate the use of multi-frequency FD-DOT to improve the recovery accuracy of scattering coefficient, which is of great interest to cancer study. A new method called the clustered sparsity reconstruction (CSR) is proposed to reconstruct the absorption and scattering coefficients jointly. We conduct numerical simulations for FD-DOT image reconstruction with multi-modulation frequencies. The numerical results show that the recovery accuracy of scattering coefficient can be significantly improved using multi-frequency data and the proposed CSR method. It is interesting to demonstrate that the combination of two modulation frequencies results in the best reconstruction accuracy in terms of contrast-to-noise ratio (CNR) and root-mean-square error (RMSE), while more number of modulation frequencies does not improve the image quality much.

Multi-modal diffuse optical techniques for breast cancer neoadjuvant chemotherapy monitoring (Conference Presentation)

We present high spatial density, multi-modal, parallel-plate Diffuse Optical Tomography (DOT) imaging systems for the purpose of breast tumor detection. One hybrid instrument provides time domain (TD) and continuous wave (CW) DOT at 64 source fiber positions. The TD diffuse optical spectroscopy with PMT- detection produces low-resolution images of absolute tissue scattering and absorption while the spatially dense array of CCD-coupled detector fibers (108 detectors) provides higher-resolution CW images of relative tissue optical properties. Reconstruction of the tissue optical properties, along with total hemoglobin concentration and tissue oxygen saturation, is performed using the TOAST software suite. Comparison of the spatially-dense DOT images and MR images allows for a robust validation of DOT against an accepted clinical modality. Additionally, the structural information from co-registered MR images is used as a spatial prior to improve the quality of the functional optical images and provide more accurate quantification of the optical and hemodynamic properties of tumors. We also present an optical-only imaging system that provides frequency domain (FD) DOT at 209 source positions with full CCD detection and incorporates optical fringe projection profilometry to determine the breast boundary. This profilometry serves as a spatial constraint, improving the quality of the DOT reconstructions while retaining the benefits of an optical-only device. We present initial images from both human subjects and phantoms to display the utility of high spatial density data and multi-modal information in DOT reconstruction with the two systems.

Intraoperative NIR Diffuse Optical Tomography System Based On Spatially Modulated Illumination Using The DLP4500 Evaluation Module (Conference Presentation)

We present a biomedical application of Digital Micro-mirror technologies by adapting the DLP4500 module for quasi real-time intraoperative tumor imaging. Fluorescence image guided surgery has been increasingly popular due to its ability to inform surgeons about tumor boundaries in real-time. We have extended this technique to provide 3D tomographic images of a tumor, by adapting a DLP4500 device to illuminate the surgical field with spatially modulated near-infrared (NIR) light. We combine the digital micro-mirror device (DMD) with two simultaneously triggered CMOS cameras to realize a spatial frequency domain imaging system. Spatial frequency domain imaging utilizes sinusoidally modulated illumination at different spatial frequencies and three different phases; corresponding signals are readily demodulated, and analyzed to derive a 3D fluorescence image. Our DMD device is commercially modified and equipped with high-power (5W) NIR diode laser. We present a brief discussion of data acquisition using DLP4500 module, and corrections for spatial inhomogeneity and gamma adjust in order to create linear/desired sinusoidal illumination of NIR light. We discuss results from a tissue phantom study and in-vivo experiments.

Intraoperative spatial frequency domain diffuse optical tomography with indo-cyanine green (ICG) fluorescence contrast (Conference Presentation)

Surgical resection is the most effective treatment strategy for solid tumors, but complete removal of the tumor is critical for post-surgical recovery/long-term survival and is dependent on correct identification of the tumor margin and accurate excision of microscopic residual tumor in the surgical field. Fluorescence image guided surgery is an emerging technique that has shown promise for intraoperative location of tumors and tumor margins. Current versions of such intraoperative fluorescence imaging, however, are generally limited to 2D near-surface images, i.e., without information about tumor depth. Here we present an intraoperative fluorescence imaging system for 3D volumetric imaging of tumors; the system uses spatial frequency domain diffuse optical tomography with an analytic inversion reconstruction method. The new instrument can derive depth-sensitive 3D tumor images at depths up to 1 cm, and it employs compact epi-imaging and illumination suitable for the operating room, with quasi-real-time image reconstruction for surgical visualization. We present experimental results with FDA-approved Indocynanine Green using an extensive array of tissue phantoms and in a pilot in-vivo study.