Michael A. Khalil

Digital optical tomography system for dynamic breast imaging

Diffuse optical tomography has shown promising results as a tool for breast cancer screening and monitoring response to chemotherapy. Dynamic imaging of the transient response of the breast to an external stimulus, such as pressure or a respiratory maneuver, can provide additional information that can be used to detect tumors. We present a new digital continuous-wave optical tomography system designed to simultaneously image both breasts at fast frame rates and with a large number of sources and detectors. The system uses a master-slave digital signal processor-based detection architecture to achieve a dynamic range of 160 dB and a frame rate of 1.7 Hz with 32 sources, 64 detectors, and 4 wavelengths per breast. Included is a preliminary study of one healthy patient and two breast cancer patients showing the ability to identify an invasive carcinoma based on the hemodynamic response to a breath hold.

Dynamic diffuse optical tomography imaging of peripheral arterial disease.

Peripheral arterial disease (PAD) is the narrowing of arteries due to plaque accumulation in the vascular walls. This leads to insufficient blood supply to the extremities and can ultimately cause cell death. Currently available methods are ineffective in diagnosing PAD in patients with calcified arteries, such as those with diabetes. In this paper we investigate the potential of dynamic diffuse optical tomography (DDOT) as an alternative way to assess PAD in the lower extremities. DDOT is a non-invasive, non-ionizing imaging modality that uses near-infrared light to create spatio-temporal maps of oxy- and deoxy-hemoglobin in tissue. We present three case studies in which we used DDOT to visualize vascular perfusion of a healthy volunteer, a PAD patient and a diabetic PAD patient with calcified arteries. These preliminary results show significant differences in DDOT time-traces and images between all three cases, underscoring the potential of DDOT as a new diagnostic tool.

A wireless handheld probe with spectrally constrained evolution strategies for diffuse optical imaging of tissue

We present a low-cost, portable, wireless diffuse optical imaging device. The handheld device is fast, portable, and can be applied to a wide range of both static and dynamic imaging applications including breast cancer, functional brain imaging, and peripheral artery disease. The continuous-wave probe has four near-infrared wavelengths and uses digital detection techniques to perform measurements at 2.3 Hz. Using a multispectral evolution algorithm for chromophore reconstruction, we can measure absolute oxygenated and deoxygenated hemoglobin concentration as well as scattering in tissue. Performance of the device is demonstrated using a series of liquid phantoms comprised of Intralipid(®), ink, and dye.

Measuring peripheral vascular reactivity with diffusive optical imaging

Diffuse optical imaging of the peripheral vascular reactivity is implemented at the major arteries of the foot. Transmitted light intensities are recorded in response to vascular occlusions induced by pressure cuffs. These dynamic measurements promise to help identify various peripheral vascular diseases.

Imaging of vascular dynamics within the foot using dynamic diffuse optical tomography to diagnose peripheral arterial disease

Peripheral Arterial Disease (PAD) is the narrowing of the functional area of the artery generally due to atherosclerosis. It affects between 8-12 million people in the United States and if untreated this can lead to ulceration, gangrene and ultimately amputation. The current diagnostic method for PAD is the ankle-brachial index (ABI). The ABI is a ratio of the patient’s systolic blood pressure in the foot to that of the brachial artery in the arm, a ratio below 0.9 is indicative of affected vasculature. However, this method is ineffective in patients with calcified arteries (diabetic and end-stage renal failure patients), which falsely elevates the ABI recording resulting in a false negative reading. In this paper we present our results in a pilot study to deduce optical tomography’s ability to detect poor blood perfusion in the foot. We performed an IRB approved 30 patient study, where we imaged the feet of the enrolled patients during a five stage dynamic imaging sequence. The patients were split up into three groups: 10 healthy subjects, 10 PAD patients and 10 PAD patients with diabetes and they were imaged while applying a pressure cuff to their thigh. Differences in the magnitude of blood pooling in the foot and rate at which the blood pools in the foot are all indicative of arterial disease.

Development of a dynamic optical tomographic breast imaging system with digital detection techniques

Breast cancer characteristics such as angiogenesis and hypoxia can be quantified by using optical tomography imaging to observe the hemodynamic response to an external stimulus. A digital near-infrared tomography system has been developed specifically for the purpose of dynamic breast imaging. It simultaneously acquires four frequency encoded wavelengths of light at 765, 808, 827, and 905nm in order to facilitate the functional imaging of oxy- and deoxy-hemoglobin, lipid concentration and water content. The system uses 32 source fibers to simultaneously illuminate both breasts. There are 128 detector fibers, 64 fibers for each breast, which deliver the detected light to silicon photo-detectors. The signal is conditioned by variable gain amplifiers and filters and is quantized by an analog to digital converter (ADC). The sampled signal is then passed on for processing using a Digital Signal Processor (DSP) prior to display on a host computer. The system can acquire 2.23 frames per second with a dynamic range of 236 dB.

Non-contact continuous-wave diffuse optical tomographic system to capture vascular dynamics in the foot

Dynamic optical tomographic imaging has shown promise in diagnosing and monitoring peripheral arterial disease (PAD), which affects 8 to 12 million in the United States. PAD is the narrowing of the arteries that supply blood to the lower extremities. Prolonged reduced blood flow to the foot leads to ulcers and gangrene, which makes placement of optical fibers for contact-based optical tomography systems difficult and cumbersome. Since many diabetic PAD patients have foot wounds, a non-contact interface is highly desirable. We present a novel non-contact dynamic continuous-wave optical tomographic imaging system that images the vasculature in the foot for evaluating PAD. The system images at up to 1Hz by delivering 2 wavelengths of light to the top of the foot at up to 20 source positions through collimated source fibers. Transmitted light is collected with an electron multiplying charge couple device (EMCCD) camera. We demonstrate that the system can resolve absorbers at various locations in a phantom study and show the system’s first clinical 3D images of total hemoglobin changes in the foot during venous occlusion at the thigh. Our initial results indicate that this system is effective in capturing the vascular dynamics within the foot and can be used to diagnose and monitor treatment of PAD in diabetic patients.

Modeling of the blood flow in the lower extremities for dynamic diffuse optical tomography of peripheral artery disease

Peripheral Arterial Disease (PAD) is caused by a reduction of the internal diameters of the arteries in the upper or lower extremities mainly due to atherosclerosis. If not treated, its worsening may led to a complete occlusion, causing the death of the cells lacking proper blood supply, followed by gangrene that may require chirurgical amputation. We have recently performed a clinical study in which good sensitivities and specificities were achieved with dynamic diffuse optical tomography. To gain a better understanding of the physiological foundations of many of the observed effects, we started to develop a mathematical model for PAD. The model presented in this work is based on a multi-compartment Windkessel model, where the vasculature in the leg and foot is represented by resistors and capacitors, the blood pressure with a voltage drop, and the blood flow with a current. Unlike existing models, the dynamics induced by a thigh-pressure-cuff inflation and deflation during the measurements are taken into consideration. This is achieved by dynamically varying the resistances of the large veins and arteries. By including the effects of the thigh-pressure cuff, we were able to explain many of the effects observed during our dynamic DOT measurements, including the hemodynamics of oxy- and deoxy-hemoglobin concentration changes. The model was implemented in MATLAB and the simulations were normalized and compared with the blood perfusion obtained from healthy, PAD and diabetic patients. Our preliminary results show that in unhealthy patients the total system resistance is sensibly higher than in healthy patients.

Detection of peripheral arterial disease using dynamic diffuse optical tomography of vascular dynamics in the foot

We present dynamic diffuse optical tomography (DDOT) results from a 34-patient study for detecting peripheral arterial disease and patients with and without diabetes. DDOT achieved a sensitivity of 80% and a specificity of 70%.

Contact-free diffuse optical tomography system for dynamic imaging of peripheral vasculature

We present a dynamic contact-free system capable of imaging at 1Hz using 20 collimated source fibers at two wavelengths and an electron multiplying charge coupled device (EMCCD) camera for imaging vascular dynamics in the foot.