Michael Ghijsen

Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI)

In this work we present and validate a wide-field method for the real-time mapping of tissue absorption, scattering and blood flow properties over wide regions of tissue (15 cm x 15 cm) with high temporal resolution (50 frames per second). We achieve this by applying Fourier Domain demodulation techniques to coherent spatial frequency domain imaging to extract optical properties and speckle flow index from a single snapshot. Applying this technique to forearm reactive hyperemia protocols demonstrates the ability to resolve intrinsic physiological signals such as the heart beat waveform and the buildup of deoxyhemoglobin associated with oxygen consumption.

In vivo validation of quantitative frequency domain fluorescence tomography

Abstract. We have developed a hybrid frequency domain fluorescence tomography and magnetic resonance imaging system (MRI) for small animal imaging. The main purpose of this system is to obtain quantitatively accurate fluorescence concentration and lifetime images using a multi-modality approach. In vivo experiments are undertaken to evaluate the system. We compare the recovered fluorescence parameters with and without MRI structural a priori information. In addition, we compare two optical background heterogeneity correction methods: Born normalization and utilizing diffuse optical tomography (DOT) functional a priori information. The results show that the concentration and lifetime of a 4.2-mm diameter indocyanine green inclusion located 15 mm deep inside a rat can be recovered with less than a 5% error when functional a priori information from DOT and structural a priori information from MRI are utilized.

Development of a hybrid MRI and fluorescence tomography system for small animal imaging

Fluorescence diffuse optical tomography (FT) is a molecular imaging technique that can create images of spatially resolved fluorophore concentrations and fluorescence lifetimes. One problem faced by FT is that the recovered fluorophore parameters greatly depend on the size and depth of the inclusion due to the ill-posedness of the FT inverse problem. Structural a priori information from imaging modalities with high spatial resolution is demonstrated to significantly improve the accuracy of the FT reconstruction. We have constructed a hybrid FT/MRI system for small animal imaging in this study. Near-infrared light was delivered and collected by optical fibers that connect the FT/MRI system to the interface in the MRI bore. We investigated the feasibility of a photo-multiplier tube (PMT) based detection system that acquired time-resolved data in the frequency domain. Phantom studies were used to evaluate the performance of the combined system. The concentration and lifetime maps were reconstructed with and without the structural a priori information obtained from MRI. ICG and DTTCI, two fluorophores with similar excitation and emission spectra but different lifetimes, were used in this evaluation. Specifically, we showed that the PMT-based frequency domain hybrid system was capable of differentiating between two fluorophores with different fluorescence lifetimes. Furthermore, this process was shown to be more accurate when MR a priori is used.

Optimal analysis method for dynamic contrast-enhanced diffuse optical tomography

Diffuse Optical Tomography (DOT) is an optical imaging modality that has various clinical applications. However, the spatial resolution and quantitative accuracy of DOT is poor due to strong photon scatting in biological tissue. Structural a priori information from another high spatial resolution imaging modality such as Magnetic Resonance Imaging (MRI) has been demonstrated to significantly improve DOT accuracy. In addition, a contrast agent can be used to obtain differential absorption images of the lesion by using dynamic contrast enhanced DOT (DCE-DOT). This produces a relative absorption map that consists of subtracting a reconstructed baseline image from reconstructed images in which optical contrast is included. In this study, we investigated and compared different reconstruction methods and analysis approaches for regular endogenous DOT and DCE-DOT with and without MR anatomical a priori information for arbitrarily-shaped objects. Our phantom and animal studies have shown that superior image quality and higher accuracy can be achieved using DCE-DOT together with MR structural a priori information. Hence, implementation of a combined MRI-DOT system to image ICG enhancement can potentially be a promising tool for breast cancer imaging.

Evaluation of a multi-wavelength laser array with diffuse optical tomography

Diffuse Optical Tomography (DOT) is a new and promising medical imaging modality which uses near-infrared light to probe tissue properties. Using multiple wavelengths of light can provide important information about tissue metabolism and cancer malignancy. Unfortunately, in most DOT acquisition schemes, acquiring data for each wavelength has a multiplicative effect on the overall imaging time. In this paper, we evaluate a new multiple wavelength laser module (Praevium Research Inc.) with 12 laser diodes all coupled to a single output fiber. When used in conjunction with a cooled spectrometer, it allows simultaneous multi-wavelength data acquisition and hence, higher temporal resolution.

Quantitative real-time optical imaging of the tissue metabolic rate of oxygen consumption

Abstract. The tissue metabolic rate of oxygen consumption (tMRO2) is a clinically relevant marker for a number of pathologies including cancer and arterial occlusive disease. We present and validate a noncontact method for quantitatively mapping tMRO2 over a wide, scalable field of view at 16  frames  /  s. We achieve this by developing a dual-wavelength, near-infrared coherent spatial frequency-domain imaging (cSFDI) system to calculate tissue optical properties (i.e., absorption, μa, and reduced scattering, μs′, parameters) as well as the speckle flow index (SFI) at every pixel. Images of tissue oxy- and deoxyhemoglobin concentration (  [  HbO2  ]   and [HHb]) are calculated from optical properties and combined with SFI to calculate tMRO2. We validate the system using a series of yeast-hemoglobin tissue-simulating phantoms and conduct in vivo tests in humans using arterial occlusions that demonstrate sensitivity to tissue metabolic oxygen debt and its repayment. Finally, we image the impact of cyanide exposure and toxicity reversal in an in vivo rabbit model showing clear instances of mitochondrial uncoupling and significantly diminished tMRO2. We conclude that dual-wavelength cSFDI provides rapid, quantitative, wide-field mapping of tMRO2 that can reveal unique spatial and temporal dynamics relevant to tissue pathology and viability.

Algorithmic processing of intrinsic signals in affixed transmission speckle analysis (ATSA) (Conference Presentation)

Affixed Transmission Speckle Analysis (ATSA) is a method recently developed to measure blood flow that is based on laser speckle imaging miniaturized into a clip-on form factor the size of a pulse-oximeter. Measuring at a rate of 250 Hz, ATSA is capable or obtaining the cardiac waveform in blood flow data, referred to as the Speckle-Plethysmogram (SPG). ATSA is also capable of simultaneously measuring the Photoplethysmogram (PPG), a more conventional signal related to light intensity. In this work we present several novel algorithms for extracting physiologically relevant information from the combined SPG-PPG waveform data. First we show that there is a slight time-delay between the SPG and PPG that can be extracted computationally. Second, we present a set of frequency domain algorithms that measure harmonic content on pulse-by-pulse basis for both the SPG and PPG. Finally, we apply these algorithms to data obtained from a set of subjects including healthy controls and individuals with heightened cardiovascular risk. We hypothesize that the time-delay and frequency content are correlated with cardiovascular health; specifically with vascular stiffening.

In vivo tumor characterization using both MR and optical contrast agents with a hybrid MRI-DOT system

Dynamic contrast enhanced MRI (DCE-MRI) has been proven to be the most sensitive modality in detecting breast lesions. Currently available MR contrast agent, Gd-DTPA, is a low molecular weight extracellular agent and can diffuse freely from the vascular space into interstitial space. Due to this reason, DCE-MRI has low sensitivity in differentiating benign and malignant tumors. Meanwhile, diffuse optical tomography (DOT) can be used to provide enhancement kinetics of an FDA approved optical contrast agent, ICG, which behaves like a large molecular weight optical agent due to its binding to albumin. The enhancement kinetics of ICG may have a potential to distinguish between the malignant and benign tumors and hence improve the specificity. Our group has developed a high speed hybrid MRI-DOT system. The DOT is a fully automated, MR-compatible, multi-frequency and multi-spectral imaging system. Fischer-344 rats bearing subcutaneous R3230 tumor are injected simultaneously with Gd-DTPA (0.1nmol/kg) and IC-Green (2.5mg/kg). The enhancement kinetics of both contrast agents are recorded simultaneously with this hybrid MRI-DOT system and evaluated for different tumors.

Design of a multimodality breast-like phantom for combined diffuse optical tomography and ultrasound tomography (DOT-UST)

The initial steps in fabricating a multimodality imaging phantom for combined diffuse optical tomography and ultrasound tomography (DOT-UST) are completed. Phantoms are intended to mimic the optical and acoustic properties of breast tissue for near infrared light and ultrasound in the vicinity of 2 MHz. So far, a prototype ultrasound tomography system has been designed and the acoustic attenuation coefficient of glass beads has been characterized. Furthermore, 8 cm diameter homogeneous cylindrical phantoms have been successfully constructed and it has been shown that an inclusion with object to background contrast of three can be comfortably detected with the prototype system.