Real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy

Purpose: To develop an algorithm for real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy. Methods: Given a set of volumetric images of a patient at N breathing phases as the training data, we perform deformable image registration between a reference phase and the other N-1 phases, resulting in N-1 deformation vector fields (DVFs). These DVFs can be represented efficiently by a few eigenvectors and coefficients obtained from principal component analysis (PCA). By varying the PCA coefficients, we can generate new DVFs, which, when applied on the reference image, lead to new volumetric images. We then can reconstruct a volumetric image from a single projection image by optimizing the PCA coefficients such that its computed projection matches the measured one. The 3D location of the tumor can be derived by applying the inverted DVF on its position in the reference image. Our algorithm was implemented on graphics processing units (GPUs) to achieve real-time efficiency. We generated the training data using a realistic and dynamic mathematical phantom with 10 breathing phases. The testing data were 360 cone beam projections corresponding to one gantry rotation, simulated using the same phantom with a 50% increase in breathing amplitude. Results: The average relative image intensity error of the reconstructed volumetric images is 6.9% +/- 2.4%. The average 3D tumor localization error is 0.8 mm +/- 0.5 mm. On an NVIDIA Tesla C1060 GPU card, the average computation time for reconstructing a volumetric image from each projection is 0.24 seconds (range: 0.17 and 0.35 seconds). Conclusions: We have shown the feasibility of reconstructing volumetric images and localizing tumor positions in 3D in near real-time from a single x-ray image.Comment: 8 pages, 3 figures, submitted to Medical Physics Lette

NONINVASIVE MULTIMODAL DIFFUSE OPTICAL IMAGING OF VULNERABLE TISSUE HEMODYNAMICS

Measurement of tissue hemodynamics provides vital information for the assessment of tissue viability. This thesis reports three noninvasive near-infrared diffuse optical systems for spectroscopic measurements and tomographic imaging of tissue hemodynamics in vulnerable tissues with the goal of disease diagnosis and treatment monitoring. A hybrid near-infrared spectroscopy/diffuse correlation spectroscopy (NIRS/DCS) instrument with a contact fiber-optic probe was developed and utilized for simultaneous and continuous monitoring of blood flow (BF), blood oxygenation, and oxidative metabolism in exercising gastrocnemius. Results measured by the hybrid NIRS/DCS instrument in 37 subjects (mean age: 67 ± 6) indicated that vitamin D supplement plus aerobic training improved muscle metabolic function in older population. To reduce the interference and potential infection risk on vulnerable tissues caused by the contact measurement, a noncontact diffuse correlation spectroscopy/tomography (ncDCS/ncDCT) system was then developed. The ncDCS/ncDCT system employed optical lenses to project limited numbers of sources and detectors on the tissue surface. A motor-driven noncontact probe scanned over a region of interest to collect boundary data for three dimensional (3D) tomographic imaging of blood flow distribution. The ncDCS was tested for BF measurements in mastectomy skin flaps. Nineteen (19) patients underwent mastectomy and implant-based breast reconstruction were measured before and immediately after mastectomy. The BF index after mastectomy in each patient was normalized to its baseline value before surgery to get relative BF (rBF). Since rBF values in the patients with necrosis (n = 4) were significantly lower than those without necrosis (n = 15), rBF levels can be used to predict mastectomy skin flap necrosis. The ncDCT was tested for 3D imaging of BF distributions in chronic wounds of 5 patients. Spatial variations in BF contrasts over the wounded tissues were observed, indicating the capability of ncDCT in detecting tissue hemodynamic heterogeneities. To improve temporal/spatial resolution and avoid motion artifacts due to a long mechanical scanning of ncDCT, an electron-multiplying charge-coupled device based noncontact speckle contrast diffuse correlation tomography (scDCT) was developed. Validation of scDCT was done by imaging both high and low BF contrasts in tissue-like phantoms and human forearms. In a wound imaging study using scDCT, significant lower BF values were observed in the burned areas/volumes compared to surrounding normal tissues in two patients with burn. One limitation in this study was the potential influence of other unknown tissue optical properties such as tissue absorption coefficient (µa) on BF measurements. A new algorithm was then developed to extract both µa and BF using light intensities and speckle contrasts measured by scDCT at multiple source-detector distances. The new algorithm was validated using tissue-like liquid phantoms with varied values of µa and BF index. In-vivo validation and application of the innovative scDCT technique with the new algorithm is the subject of future work

Development of Portable Diffuse Optical Spectroscopic Systems For Treatment Monitoring

The goal of this dissertation is to demonstrate the utility of portable, small-scale diffuse optical spectroscopic (DOS) systems for the diagnosis and treatment monitoring of various diseases. These systems employ near-infrared light (wavelength range of 650nm to 950nm) to probe human tissue and are sensitive to changes in scattering and absorption properties of tissues. The absorption is mainly influenced by the components of blood, namely oxy- and deoxy-hemoglobin (HbO2 and Hb) and parameters that can be derived from them (e.g. total hemoglobin concentration [THb] and oxygen saturation, StO2). Therefore, I focused on diseases in which these parameters change, which includes vascular diseases such as Peripheral Atrial Disease (PAD) and Infantile Hemangiomas (IH) as well as musculoskeletal autoimmune diseases such as Rheumatoid Arthritis (RA). In each of these specific diseases, current monitoring techniques are limited by their sensitivity to disease progression or simply do not exist as a quantitative metric. As part of this project, I first designed and built a wireless handheld DOS device (WHDD) that can perform DOS measurements at various tissue depths. This device was used in a 15-patient pilot study for infantile hemangiomas (IH) to differentiate diseased skin from normal skin and monitor the vascular changes during intervention. In another study, I compare the ultra-small form- factor WHDD’s ability to monitor synovitis and disease progression during a patient’s treatment of RA against the capabilities of a proven frequency domain optical tomographic (FDOT) system that has shown to differentiate patients with and without RA. Learning from clinical utility of the WHDD from these two studies, I adapted the WHDD technology to develop a compact multi- channel DOS measurement system to monitor perfusion changes in the lower extremities before and after surgical intervention for patients with peripheral artery disease (PAD). Using this multi- channel system, which we called the vascular optical spectroscopic measurement (VOSM) system, our group conducted a 20-subject pilot study to quantify its ability to monitor blood perfusion before and after revascularization of stenotic arteries in the lower extremities. This proof-of- concept study demonstrated how DOS may help vascular surgeons perform revascularization procedures in the operating room and assists in post-operative treatment monitoring of vascular diseases

Improvements in Cardiac Spect/CT for the Purpose of Tracking Transplanted Cells

Regenerative therapy via stem cell transplantation has received increased attention to help treat the myocardial injury associated with heart disease. Currently, the hybridisation of SPECT with X-ray CT is expanding the utility of SPECT. This thesis compared two SPECT/CT systems for attenuation correction using slow or fast-CT attenuation maps (mu-maps). We then developed a method to localize transplanted cells in relation to compromised blood flow in the myocardium following a myocardial infarction using SPECT/CT. Finally, a method to correct for image truncation was studied for a new SPECT/CT design that incorporated small field-of-view (FOV) detectors. Computer simulations compared gated-SPECT reconstructions using slow-CT and fast-CT mu-maps with gated-CT mu-maps. Using fast-CT mu-maps improved the Root Mean Squared (RMS) error from 4.2% to 4.0%. Three canine experiments were performed comparing SPECT/CT reconstruction using the Infinia/Hawkeye-4 (slow-CT) and Symbia T6 (fast-CT). Canines were euthanized prior to imaging, and then ventilated. The results showed improvements in both RMS errors and correlation coefficients for all canines. A first-pass contrast CT imaging technique can identify regions of myocardial infarction and can be fused with SPECT. Ten canines underwent surgical ligation of the left-anterior-descending artery. Cells were labeled with 111In-tropolone and transplanted into the myocardium. SPECT/CT was performed on day of transplantation, 4, and 10 days post-transplantation. For each imaging session first-pass perfusion CT was performed and successfully delineated the infarct zone. Delayed-enhanced MRI was performed and correlated well with first-pass CT. Contrast-to-noise ratios were calculated for 111In-SPECT and suggested that cells can be followed for 11 effective half-lives. We evaluated a modified SPECT/CT acquisition and reconstruction method for truncated SPECT. Cardiac SPECT/CT scans were acquired in 14 patients. The original projections were truncated to simulate a small FOV acquisition. Data was reconstructed in three ways: non-truncated and standard reconstruction (NTOSEM), which was our gold-standard; truncated and standard reconstruction (TOSEM); and truncated and a modified reconstruction (TMOSEM). Compared with NTOSEM, small FOV imaging incurred an average cardiac count ratio error greater than 100% using TOSEM and 8.9% using TMOSEM. When we plotted NTOSEM against TOSEM and TMOSEM the correlation coefficient was 0.734 and 0.996 respectively

Reconstruction of coronary arteries from X-ray angiography: A review.

Despite continuous progress in X-ray angiography systems, X-ray coronary angiography is fundamentally limited by its 2D representation of moving coronary arterial trees, which can negatively impact assessment of coronary artery disease and guidance of percutaneous coronary intervention. To provide clinicians with 3D/3D+time information of coronary arteries, methods computing reconstructions of coronary arteries from X-ray angiography are required. Because of several aspects (e.g. cardiac and respiratory motion, type of X-ray system), reconstruction from X-ray coronary angiography has led to vast amount of research and it still remains as a challenging and dynamic research area. In this paper, we review the state-of-the-art approaches on reconstruction of high-contrast coronary arteries from X-ray angiography. We mainly focus on the theoretical features in model-based (modelling) and tomographic reconstruction of coronary arteries, and discuss the evaluation strategies. We also discuss the potential role of reconstructions in clinical decision making and interventional guidance, and highlight areas for future research

3-D lung deformation and function from respiratory-gated 4-D x-ray CT images : application to radiation treatment planning.

Many lung diseases or injuries can cause biomechanical or material property changes that can alter lung function. While the mechanical changes associated with the change of the material properties originate at a regional level, they remain largely asymptomatic and are invisible to global measures of lung function until they have advanced significantly and have aggregated. In the realm of external beam radiation therapy of patients suffering from lung cancer, determination of patterns of pre- and post-treatment motion, and measures of regional and global lung elasticity and function are clinically relevant. In this dissertation, we demonstrate that 4-D CT derived ventilation images, including mechanical strain, provide an accurate and physiologically relevant assessment of regional pulmonary function which may be incorporated into the treatment planning process. Our contributions are as follows: (i) A new volumetric deformable image registration technique based on 3-D optical flow (MOFID) has been designed and implemented which permits the possibility of enforcing physical constraints on the numerical solutions for computing motion field from respiratory-gated 4-D CT thoracic images. The proposed optical flow framework is an accurate motion model for the thoracic CT registration problem. (ii) A large displacement landmark-base elastic registration method has been devised for thoracic CT volumetric image sets containing large deformations or changes, as encountered for example in registration of pre-treatment and post-treatment images or multi-modality registration. (iii) Based on deformation maps from MOFIO, a novel framework for regional quantification of mechanical strain as an index of lung functionality has been formulated for measurement of regional pulmonary function. (iv) In a cohort consisting of seven patients with non-small cell lung cancer, validation of physiologic accuracy of the 4-0 CT derived quantitative images including Jacobian metric of ventilation, Vjac, and principal strains, (V?1, V?2, V?3, has been performed through correlation of the derived measures with SPECT ventilation and perfusion scans. The statistical correlations with SPECT have shown that the maximum principal strain pulmonary function map derived from MOFIO, outperforms all previously established ventilation metrics from 40-CT. It is hypothesized that use of CT -derived ventilation images in the treatment planning process will help predict and prevent pulmonary toxicity due to radiation treatment. It is also hypothesized that measures of regional and global lung elasticity and function obtained during the course of treatment may be used to adapt radiation treatment. Having objective methods with which to assess pre-treatment global and regional lung function and biomechanical properties, the radiation treatment dose can potentially be escalated to improve tumor response and local control

Ultrasound and photoacoustic methods for anatomic and functional imaging in image guided radiation therapy

(MATERIAL and METHODS) First, we define the physical principals and optimal protocols that provide contrast when imaging with US and the transducer properties contributing to resolution limits. The US field of view (FOV) was characterized to determine the optimal settings with regard to imaging depth, focal region, with and without harmonic imaging, and artifact identification. This will allow us to determine the minimum errors expected when registering multimodal volumes (CT, US, CBCT). Next, we designed an in-house integrated US manipulator and platform to relate CT, 3D-US and linear accelerator coordinate systems. To validate our platform, an agar-based phantom with measured densities and speed-of-sound consistent with tissues surrounding the bladder was fabricated. This phantom was rotated relative to the CT and US coordinate systems and imaged with both modalities. These CT and 3D-US images were imported into the treatment planning system, where US-to-US and US-to-CT images were co-registered and the registration matrix used to re-align the phantom relative to the linear accelerator. The measured precision in the phantom setup, which is defined by the standard deviation of the transformation matrix components, was consistent with and exceeding acceptable clinical patient re-alignments (2 mm). Statistical errors from US-US registrations for different patient orientations ranged from 0.06-1.66 mm for x, y, and z translational components, and 0.00-1.05 degrees for rotational components. Statistical errors from US-CT registrations were 0.23-1.18 mm for the x, y and z translational components, and 0.08-2.52 degrees for the rotational components. The high precision in the multimodal registrations suggest the ability to use US for patient positioning when targeting abdominal structures. We are now testing this on a dog patient to obtain both inter and intra-fractional positional errors. The objective of this experiment is to confirm Hill’s equation describing the relationship between hemoglobin saturation (SaO2) and the partial pressure of dissolved oxygen (pO2). The relationship is modeled as a sigmoidal curve that is a function of two parameters – the Hill coefficient, n, and the net association constant of HbO2, K (or pO2 at 50% SaO2). The goal is to noninvasively measure SaO2 in breast tumors in mice using photoacoustic computed tomographic (PCT) imaging and compare those measurements to a gold standard for pO2 using the OxyLite probe. First, a calibration study was performed to measure the SaO2 (co-oximeter) and pO2 (Oxylite probe) in blood using Hill’s equation (P50=23.2 mmHg and n=2.26). Next, non-invasive localized measurements of SaO2 in MDA-MD-231 and MCF7 breast tumors using PCT spectroscopic methods were compared to pO 2 levels using Oxylite probe. The fitted results for MCF7 and MDA-MD-231 data resulted in a P50 of 17.2 mmHg and 20.7 mmHg and a n of 1.76 and 1.63, respectively. The lower value of the P50 is consistent with tumors being more acidic than healthy tissue. Current work applying photon fluence corrections and image artifact reduction is expected to improve the quality of the results. In summary, this study demonstrates that photoacoustic imaging can be used to monitor tumor oxygenation, and its potential use to investigate the effectiveness of radiation therapy and the ability to adapt therapeutic protocols

Mathematics and Algorithms in Tomography

This is the eighth Oberwolfach conference on the mathematics of tomography. Modalities represented at the workshop included X-ray tomography, sonar, radar, seismic imaging, ultrasound, electron microscopy, impedance imaging, photoacoustic tomography, elastography, vector tomography, and texture analysis

The role of OCT-A in retinal disease management

Optical coherence tomography angiography (OCT-A) is a non-invasive, non-dye-based imaging modality that has the potential to enhance our understanding of retinal diseases. While this rapidly advancing imaging modality offers great potential, there is a need for community-wide understanding of the range of technologies and methods for interpreting the images, as well as a need to enhance understanding of images from disease-free eyes for reference when screening for retinal diseases. Importantly, clinical trials have been designed without OCT-A-based endpoints; therefore, caution is required when making treatment decisions based on OCT-A imaging alone. With this in mind, a full understanding of the advantages and limitations of OCT-A will be vital for effective development of the technique within the field of ophthalmology. On behalf of the Vision Academy Steering Committee (sponsored by Bayer), this publication summarizes the views of the authors on the current use of OCT-A imaging and explores its potential for future applications in research and clinical practice