Clinical Translation of a Novel Hand-held Optical Imager for Breast Cancer Diagnosis

Optical imaging is an emerging technology towards non-invasive breast cancer diagnostics. In recent years, portable and patient comfortable hand-held optical imagers are developed towards two-dimensional (2D) tumor detections. However, these imagers are not capable of three-dimensional (3D) tomography because they cannot register the positional information of the hand-held probe onto the imaged tissue. A hand-held optical imager has been developed in our Optical Imaging Laboratory with 3D tomography capabilities, as demonstrated from tissue phantom studies. The overall goal of my dissertation is towards the translation of our imager to the clinical setting for 3D tomographic imaging in human breast tissues. A systematic experimental approach was designed and executed as follows: (i) fast 2D imaging, (ii) coregistered imaging, and (iii) 3D tomographic imaging studies. (i) Fast 2D imaging was initially demonstrated in tissue phantoms (1% Liposyn solution) and in vitro (minced chicken breast and 1% Liposyn). A 0.45 cm3 fluorescent target at 1:0 contrast ratio was detectable up to 2.5 cm deep. Fast 2D imaging experiments performed in vivo with healthy female subjects also detected a 0.45 cm3 fluorescent target superficially placed ~2.5 cm under the breast tissue. (ii) Coregistered imaging was automated and validated in phantoms with ~0.19 cm error in the probe’s positional information. Coregistration also improved the target depth detection to 3.5 cm, from multi-location imaging approach. Coregistered imaging was further validated in-vivo, although the error in probe’s positional information increased to ~0.9 cm (subject to soft tissue deformation and movement). (iii) Three-dimensional tomography studies were successfully demonstrated in vitro using 0.45 cm3 fluorescence targets. The feasibility of 3D tomography was demonstrated for the first time in breast tissues using the hand-held optical imager, wherein a 0.45 cm3 fluorescent target (superficially placed) was recovered along with artifacts. Diffuse optical imaging studies were performed in two breast cancer patients with invasive ductal carcinoma. The images showed greater absorption at the tumor cites (as observed from x-ray mammography, ultrasound, and/or MRI). In summary, my dissertation demonstrated the potential of a hand-held optical imager towards 2D breast tumor detection and 3D breast tomography, holding a promise for extensive clinical translational efforts

Two-dimensional Fast Surface Imaging Using a Handheld Optical Device: In Vitro and In Vivo Fluorescence Studies

Near-infrared (NIR) optical imaging is a noninvasive and nonionizing modality that is emerging as a diagnostic tool for breast cancer. The handheld optical devices developed to date using the NIR technology are predominantly developed for spectroscopic applications. A novel handheld probe–based optical imaging device has been recently developed toward area imaging and tomography applications. The three-dimensional (3D) tomographic imaging capabilities of the device have been demonstrated from previous fluorescence studies on tissue phantoms. In the current work, fluorescence imaging studies are performed on tissue phantoms, in vitro, and in vivo tissue models to demonstrate the fast two-dimensional (2D) surface imaging capabilities of this flexible handheld-based optical imaging device, toward clinical breast imaging studies. Preliminary experiments were performed using target( s) of varying volume (0.23 and 0.45 cm3) and depth (1-2 cm), using indocyanine green as the fluorescence contrast agent in liquid phantom, in vitro, and in vivo tissue models. The feasibility of fast 2D surface imaging (∼5 seconds) over large surface areas of 36 cm2 was demonstrated from various tissue models. The surface images could differentiate the target(s) from the background, allowing a rough estimate of the target’s location before extensive 3D tomographic analysis (future studies)

Hybrid-dual-fourier tomographic algorithm for a fast three-dimensionial optical image reconstruction in turbid media

A reconstruction technique for reducing computation burden in the 3D image processes, wherein the reconstruction procedure comprises an inverse and a forward model. The inverse model uses a hybrid dual Fourier algorithm that combines a 2D Fourier inversion with a 1D matrix inversion to thereby provide high-speed inverse computations. The inverse algorithm uses a hybrid transfer to provide fast Fourier inversion for data of multiple sources and multiple detectors. The forward model is based on an analytical cumulant solution of a radiative transfer equation. The accurate analytical form of the solution to the radiative transfer equation provides an efficient formalism for fast computation of the forward model

Passive element enriched photoacoustic computed tomography (PER PACT) for simultaneous imaging of acoustic propagation properties and light absorption\ud

We present a ‘hybrid’ imaging approach which can image both light absorption properties and acoustic transmission properties of an object in a two-dimensional slice using a computed tomography (CT) photoacoustic imager. The ultrasound transmission measurement method uses a strong optical absorber of small cross-section placed in the path of the light illuminating the sample. This absorber, which we call a passive element acts as a source of ultrasound. The interaction of ultrasound with the sample can be measured in transmission, using the same ultrasound detector used for photoacoustics. Such measurements are made at various angles around the sample in a CT approach. Images of the ultrasound propagation parameters, attenuation and speed of sound, can be reconstructed by inversion of a measurement model. We validate the method on specially designed phantoms and biological specimens. The obtained images are quantitative in terms of the shape, size, location, and acoustic properties of the examined heterogeneitie

Gen-2 Hand-Held Optical Imager towards Cancer Imaging: Reflectance and Transillumination Phantom Studies

Hand-held near-infrared (NIR) optical imagers are developed by various researchers towards non-invasive clinical breast imaging. Unlike these existing imagers that can perform only reflectance imaging, a generation-2 (Gen-2) hand-held optical imager has been recently developed to perform both reflectance and transillumination imaging. The unique forked design of the hand-held probe head(s) allows for reflectance imaging (as in ultrasound) and transillumination or compressed imaging (as in X-ray mammography). Phantom studies were performed to demonstrate two-dimensional (2D) target detection via reflectance and transillumination imaging at various target depths (1–5 cm deep) and using simultaneous multiple point illumination approach. It was observed that 0.45 cc targets were detected up to 5 cm deep during transillumination, but limited to 2.5 cm deep during reflectance imaging. Additionally, implementing appropriate data post-processing techniques along with a polynomial fitting approach, to plot 2D surface contours of the detected signal, yields distinct target detectability and localization. The ability of the gen-2 imager to perform both reflectance and transillumination imaging allows its direct comparison to ultrasound and X-ray mammography results, respectively, in future clinical breast imaging studies

Optical imaging for breast cancer prescreening

Breast cancer prescreening is carried out prior to the gold standard screening using X-ray mammography and/or ultrasound. Prescreening is typically carried out using clinical breast examination (CBE) or self-breast examinations (SBEs). Since CBE and SBE have high false-positive rates, there is a need for a low-cost, noninvasive, non-radiative, and portable imaging modality that can be used as a prescreening tool to complement CBE/SBE. This review focuses on the various hand-held optical imaging devices that have been developed and applied toward early-stage breast cancer detection or as a prescreening tool via phantom, in vivo, and breast cancer imaging studies. Apart from the various optical devices developed by different research groups, a wide-field fiber-free near-infrared optical scanner has been developed for transillumination-based breast imaging in our Optical Imaging Laboratory. Preliminary in vivo studies on normal breast tissues, with absorption-contrasted targets placed in the intramammary fold, detected targets as deep as 8.8 cm. Future work involves in vivo imaging studies on breast cancer subjects and comparison with the gold standard X-ray mammography approach

Time-domain functional diffuse optical tomography system based on fiber-free silicon photomultipliers

Based on recent developments in both single-photon detectors and timing electronic circuits, we designed a compact and cost effective time-domain diffuse optical tomography system operated at 1 Hz acquisition rate, based on eight silicon photomultipliers and an 8-channel time-to-digital converter. The compact detectors are directly hosted on the probe in a circular arrangement around a single light injection fiber, so to maximize light harvesting. Tomography is achieved exploiting the depth sensitivity that is encoded in the arrival time of detected photons. The system performances were evaluated on simulations to assess possible the limitations arising from the use of a single injection point, and then on phantoms and in vivo to prove the eligibility of these technologies for diffuse optical tomography

System Optimization and Iterative Image Reconstruction in Photoacoustic Computed Tomography for Breast Imaging

Photoacoustic computed tomography(PACT), also known as optoacoustic tomography (OAT), is an emerging imaging technique that has developed rapidly in recent years. The combination of the high optical contrast and the high acoustic resolution of this hybrid imaging technique makes it a promising candidate for human breast imaging, where conventional imaging techniques including X-ray mammography, B-mode ultrasound, and MRI suffer from low contrast, low specificity for certain breast types, and additional risks related to ionizing radiation. Though significant works have been done to push the frontier of PACT breast imaging, it is still challenging to successfully build a PACT breast imaging system and apply it to wide clinical use because of various practical reasons. First, computer simulation studies are often conducted to guide imaging system designs, but the numerical phantoms employed in most previous works consist of simple geometries and do not reflect the true anatomical structures within the breast. Therefore the effectiveness of such simulation-guided PACT system in clinical experiments will be compromised. Second, it is challenging to design a system to simultaneously illuminate the entire breast with limited laser power. Some heuristic designs have been proposed where the illumination is non-stationary during the imaging procedure, but the impact of employing such a design has not been carefully studied. Third, current PACT imaging systems are often optimized with respect to physical measures such as resolution or signal-to-noise ratio (SNR). It would be desirable to establish an assessing framework where the detectability of breast tumor can be directly quantified, therefore the images produced by such optimized imaging systems are not only visually appealing, but most informative in terms of the tumor detection task. Fourth, when imaging a large three-dimensional (3D) object such as the breast, iterative reconstruction algorithms are often utilized to alleviate the need to collect densely sampled measurement data hence a long scanning time. However, the heavy computation burden associated with iterative algorithms largely hinders its application in PACT breast imaging. This dissertation is dedicated to address these aforementioned problems in PACT breast imaging. A method that generates anatomically realistic numerical breast phantoms is first proposed to facilitate computer simulation studies in PACT. The non-stationary illumination designs for PACT breast imaging are then systematically investigated in terms of its impact on reconstructed images. We then apply signal detection theory to assess different system designs to demonstrate how an objective, task-based measure can be established for PACT breast imaging. To address the slow computation time of iterative algorithms for PACT imaging, we propose an acceleration method that employs an approximated but much faster adjoint operator during iterations, which can reduce the computation time by a factor of six without significantly compromising image quality. Finally, some clinical results are presented to demonstrate that the PACT breast imaging can resolve most major and fine vascular structures within the breast, along with some pathological biomarkers that may indicate tumor development