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.
KEYWORDS: Algorithm development, Biomedical optics, Photonics, Current controlled current source, Speckle analysis, Laser speckle imaging, Blood circulation, Signal processing, Laser development, Control systems
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.
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.
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.
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.
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.
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.
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