High Performance Optical Computed Tomography for Accurate Three-Dimensional Radiation Dosimetry

Optical computed tomography (CT) imaging of radiochromic gel dosimeters is a method for truly three-dimensional radiation dosimetry. Although optical CT dosimetry is not widely used currently due to previous concerns with speed and accuracy, the complexity of modern radiotherapy is increasing the need for a true 3D dosimeter. This thesis reports technical improvements that bring the performance of optical CT to a clinically useful level. New scanner designs and improved scanning and reconstruction techniques are described. First, we designed and implemented a new light source for a cone-beam optical CT system which reduced the scatter to primary contribution in CT projection images of gel dosimeters from approximately 25% to approximately 4%. This design, which has been commercially implemented, enables accurate and fast dosimetry. Second, we designed and constructed a new, single-ray, single-detector parallel-beam optical CT scanner. This system was able to very accurately image both absorbing and scattering objects in large volumes (15 cm diameter), agreeing within ∼1% with independent measurements. It has become a reference standard for evaluation of optical CT geometries and dosimeter formulations. Third, we implemented and characterized an iterative reconstruction algorithm for optical CT imaging of gel dosimeters. This improved image quality in optical CT by suppressing the effects of noise and artifacts by a factor of up to 5. Fourth, we applied a fiducial-based ray path measurement scheme, combined with an iterative reconstruction algorithm, to enable optical CT reconstruction in the case of refractive index mismatch between different media in the scanner’s imaged volume. This improved the practicality of optical CT, as time-consuming mixing of liquids can be avoided. Finally, we applied the new laser scanner to the difficult dosimetry task of small-field measurement. We were able to obtain beam profiles and depth dose curves for 4 fields (3x3 cm2 and below) using one 15 cm diameter dosimeter, within 2 hours. Our gel dosimetry depth-dose curves agreed within ∼1.5% with Monte Carlo simulations. In conclusion, the developments reported here have brought optical CT dosimetry to a clinically useful level. Our techniques will be used to assist future research in gel dosimetry and radiotherapy treatment techniques

해부학적 유도 PET 재구성: 매끄럽지 않은 사전 함수부터 딥러닝 접근까지

학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의과학과, 2021. 2. 이재성.Advances in simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) technology have led to an active investigation of the anatomy-guided regularized PET image reconstruction algorithm based on MR images. Among the various priors proposed for anatomy-guided regularized PET image reconstruction, Bowsher’s method based on second-order smoothing priors sometimes suffers from over-smoothing of detailed structures. Therefore, in this study, we propose a Bowsher prior based on the l1 norm and an iteratively reweighting scheme to overcome the limitation of the original Bowsher method. In addition, we have derived a closed solution for iterative image reconstruction based on this non-smooth prior. A comparison study between the original l2 and proposed l1 Bowsher priors were conducted using computer simulation and real human data. In the simulation and real data application, small lesions with abnormal PET uptake were better detected by the proposed l1 Bowsher prior methods than the original Bowsher prior. The original l2 Bowsher leads to a decreased PET intensity in small lesions when there is no clear separation between the lesions and surrounding tissue in the anatomical prior. However, the proposed l1 Bowsher prior methods showed better contrast between the tumors and surrounding tissues owing to the intrinsic edge-preserving property of the prior which is attributed to the sparseness induced by l1 norm, especially in the iterative reweighting scheme. Besides, the proposed methods demonstrated lower bias and less hyper-parameter dependency on PET intensity estimation in the regions with matched anatomical boundaries in PET and MRI. Moreover, based on the formulation of l1 Bowsher prior, the unrolled network containing the conventional maximum-likelihood expectation-maximization (ML-EM) module was also proposed. The convolutional layers successfully learned the distribution of anatomically-guided PET images and the EM module corrected the intermediate outputs by comparing them with sinograms. The proposed unrolled network showed better performance than ordinary U-Net, where the regional uptake is less biased and deviated. Therefore, these methods will help improve the PET image quality based on the anatomical side information.양전자방출단층촬영 / 자기공명영상 (PET/MRI) 동시 획득 기술의 발전으로 MR 영상을 기반으로 한 해부학적 사전 함수로 정규화 된 PET 영상 재구성 알고리즘에 대한 심도있는 평가가 이루어졌다. 해부학 기반으로 정규화 된 PET 이미지 재구성을 위해 제안 된 다양한 사전 중 2차 평활화 사전함수에 기반한 Bowsher의 방법은 때때로 세부 구조의 과도한 평활화로 어려움을 겪는다. 따라서 본 연구에서는 원래 Bowsher 방법의 한계를 극복하기 위해 l1 norm에 기반한 Bowsher 사전 함수와 반복적인 재가중치 기법을 제안한다. 또한, 우리는 이 매끄럽지 않은 사전 함수를 이용한 반복적 이미지 재구성에 대해 닫힌 해를 도출했다. 원래 l2와 제안 된 l1 Bowsher 사전 함수 간의 비교 연구는 컴퓨터 시뮬레이션과 실제 데이터를 사용하여 수행되었다. 시뮬레이션 및 실제 데이터에서 비정상적인 PET 흡수를 가진 작은 병변은 원래 Bowsher 이전보다 제안 된 l1 Bowsher 사전 방법으로 더 잘 감지되었다. 원래의 l2 Bowsher는 해부학적 영상에서 병변과 주변 조직 사이에 명확한 분리가 없을 때 작은 병변에서의 PET 강도를 감소시킨다. 그러나 제안 된 l1 Bowsher 사전 방법은 특히 반복적 재가중치 기법에서 l1 노름에 의해 유도된 희소성에 기인한 특성으로 인해 종양과 주변 조직 사이에 더 나은 대비를 보여주었다. 또한 제안된 방법은 PET과 MRI의 해부학적 경계가 일치하는 영역에서 PET 강도 추정에 대한 편향이 더 낮고 하이퍼 파라미터 종속성이 적음을 보여주었다. 또한, l1Bowsher 사전 함수의 닫힌 해를 기반으로 기존의 ML-EM (maximum-likelihood expectation-maximization) 모듈을 포함하는 펼쳐진 네트워크도 제안되었다. 컨볼루션 레이어는 해부학적으로 유도 재구성된 PET 이미지의 분포를 성공적으로 학습했으며, EM 모듈은 중간 출력들을 사이노그램과 비교하여 결과 이미지가 잘 들어맞게 수정했다. 제안된 펼쳐진 네트워크는 지역의 흡수선량이 덜 편향되고 편차가 적어, 일반 U-Net보다 더 나은 성능을 보여주었다. 따라서 이러한 방법들은 해부학적 정보를 기반으로 PET 이미지 품질을 향상시키는 데 유용할 것이다.Chapter 1. Introduction 1 1.1. Backgrounds 1 1.1.1. Positron Emission Tomography 1 1.1.2. Maximum a Posterior Reconstruction 1 1.1.3. Anatomical Prior 2 1.1.4. Proposed l_1 Bowsher Prior 3 1.1.5. Deep Learning for MR-less Application 4 1.2. Purpose of the Research 4 Chapter 2. Anatomically-guided PET Reconstruction Using Bowsher Prior 6 2.1. Backgrounds 6 2.1.1. PET Data Model 6 2.1.2. Original Bowsher Prior 7 2.2. Methods and Materials 8 2.2.1. Proposed l_1 Bowsher Prior 8 2.2.2. Iterative Reweighting 13 2.2.3. Computer Simulations 15 2.2.4. Human Data 16 2.2.5. Image Analysis 17 2.3. Results 19 2.3.1. Simulation with Brain Phantom 19 2.3.2.Human Data 20 2.4. Discussions 25 Chapter 3. Deep Learning Approach for Anatomically-guided PET Reconstruction 31 3.1. Backgrounds 31 3.2. Methods and Materials 33 3.2.1. Douglas-Rachford Splitting 33 3.2.2. Network Architecture 34 3.2.3. Dataset and Training Details 35 3.2.4. Image Analysis 36 3.3. Results 37 3.4. Discussions 38 Chapter 4. Conclusions 40 Bibliography 41 Abstract in Korean (국문 초록) 52Docto

Reduction of Limited Angle Artifacts in Medical Tomography via Image Reconstruction

Artifacts are unwanted effects in tomographic images that do not reflect the nature of the object. Their widespread occurrence makes their reduction and if possible removal an important subject in the development of tomographic image reconstruction algorithms. Limited angle artifacts are caused by the limited angular measurements, constraining the available tomographic information. This thesis focuses on reducing these artifacts via image reconstruction in two cases of incomplete measurements from: (1) the gaps left after the removal of high density objects such as dental fillings, screws and implants in computed tomography (CT) and (2) partial ring scanner configurations in positron emission tomography (PET). In order to include knowledge about the measurement and noise, prior terms were used within the reconstruction methods. Careful consideration was given to the trade-off between image blurring and noise reduction upon reconstruction of low-dose measurements.Development of reconstruction methods is an incremental process starting with testing on simple phantoms towards more clinically relevant ones by modeling the respective physical processes involved. In this work, phantoms were constructed to ensure that the proposed reconstruction methods addressed to the limited angle problem. The reconstructed images were assessed qualitatively and quantitatively in terms of noise reduction, edge sharpness and contrast recovery.Maximum a posteriori (MAP) estimation with median root prior (MRP) was selected for the reconstruction of limited angle measurements. MAP with MRP successfully reduced the artifacts caused by limited angle data in various datasets, tested with the reconstruction of both list-mode and projection data. In all cases, its performance was found to be superior to conventional reconstruction methods such as total-variation (TV) prior, maximum likelihood expectation maximization (MLEM) and filtered backprojection (FBP). MAP with MRP was also more robust with respect to parameter selection than MAP with TV prior.This thesis demonstrates the wide-range applicability of MAP with MRP in medical tomography, especially in low-dose imaging. Furthermore, we emphasize the importance of developing and testing reconstruction methods with application-specific phantoms, together with the properties and limitations of the measurements in mind

Improvements in the robustness and accuracy of bioluminescence tomographic reconstructions of distributed sources within small animals

High quality three-dimensional bioluminescence tomographic (BLT) images, if available, would constitute a major advance and provide much more useful information than the two-dimensional bioluminescence images that are frequently used today. To-date, high quality BLT images have not been available, largely because of the poor quality of the data being input into the reconstruction process. Many significant confounds are not routinely corrected for and the noise in this data is unnecessarily large and poorly distributed. Moreover, many of the design choices affecting image quality are not well considered, including choices regarding the number and type of filters used when making multispectral measurements and choices regarding the frequency and uniformity of the sampling of both the range and domain of the BLT inverse problem. Finally, progress in BLT image quality is difficult to gauge owing to a lack of realistic gold-standard references that engage the full complexity and uncertainty within a small animal BLT imaging experiment. Within this dissertation, I address all of these issues. I develop a Cerenkov-based gold-standard wherein a Positron Emission Tomography (PET) image can be used to gauge improvements in the accuracy of BLT reconstruction algorithms. In the process of creating this reference, I discover and describe corrections for several confounds that if left uncorrected would introduce artifacts into the BLT images. This includes corrections for the angle of the animal’s skin surface relative to the camera, for the height of each point on the skin surface relative to the focal plane, and for the variation in bioluminescence intensity as a function of luciferin concentration over time. Once applied, I go on to derive equations and algorithms that when employed are able to minimize the noise in the final images under the constraints of a multispectral BLT data acquisition. These equations and algorithms allow for an optimal choice of filters to be made and for the acquisition time to be optimally distributed among those filtered measurements. These optimizations make use of Barrett’s and Moore-Penrose pseudoinverse matrices which also come into play in a paradigm I describe that can be used to guide choices regarding sampling of the domain and range

On the investigation of a novel x-ray imaging techniques in radiation oncology

Radiation therapy is indicated for nearly 50% of cancer patients in Australia. Radiation therapy requires accurate delivery of ionising radiation to the neoplastic tissue and pre-treatment in situ x-ray imaging plays an important role in meeting treatment accuracy requirements. Four dimensional cone-beam computed tomography (4D CBCT) is one such pre-treatment imaging technique that can help to visualise tumour target motion due to breathing at the time of radiation treatment delivery. Measuring and characterising the target motion can help to ensure highly accurate therapeutic x-ray beam delivery. In this thesis, a novel pre-treatment x-ray imaging technique, called Respiratory Triggered 4D cone-beam Computed Tomography (RT 4D CBCT), is conceived and investigated. Specifically, the aim of this work is to progress the 4D CBCT imaging technology by investigating the use of a patient’s breathing signal to improve and optimise the use of imaging radiation in 4D CBCT to facilitate the accurate delivery of radiation therapy. These investigations are presented in three main studies: 1. Introduction to the concept of respiratory triggered four dimensional conebeam computed tomography. 2. A simulation study exploring the behaviour of RT 4D CBCT using patientmeasured respiratory data. 3. The experimental realisation of RT 4D CBCT working in a real-time acquisitions setting. The major finding from this work is that RT 4D CBCT can provide target motion information with a 50% reduction in the x-ray imaging dose applied to the patient

Optimizing Respiratory Gated Intensity Modulated Radiation Therapy Planning and Delivery of Early-Stage Non-Small Cell Lung Cancer

Stereotactic ablative body radiotherapy (SABR) is the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. However, thoracic tumours are susceptible to respiratory motion and, if unaccounted for, can potentially lead to dosimetric uncertainties. Respiratory gating is one method that limits treatment delivery to portions of the respiratory cycle, but when combined with intensity-modulated radiotherapy (IMRT), requires rigorous verification. The goal of this thesis is to optimize respiratory gated IMRT treatment planning and develop image-guided strategies to verify the dose delivery for future early-stage NSCLC patients. Retrospective treatment plans were generated for various IMRT delivery techniques, including fixed-beam, volumetric modulated arc therapy (VMAT), and helical tomotherapy. VMAT was determined the best technique for optimizing dose conformity and efficiency. A second treatment planning study that considered patients exhibiting significant tumour motion was conducted. Respiratory ungated and gated VMAT plans were compared. Significant decreases in V20Gy and V50%, predictors for radiation pneumonitis and irreversible fibrosis, respectively, were observed. The predominant uncertainty of respiratory gating lies in the ability of an external surrogate marker to accurately predict internal target motion. Intrafraction triggered kV imaging was validated in a programmable motion phantom study as a method to determine how correlated the internal and external motion are during ungated and gated VMAT deliveries and to identify potential phase shifts between the motions. KV projections acquired during gated VMAT delivery were used to reconstruct gated cone-beam CT (CBCT), providing 3D tumour position verification. Image quality and target detectability, in the presence of MV scatter from the treatment beam to the kV detector, was evaluated with various imaging parameters and under real-patient breathing motion conditions. No significant difference in image quality was observed for the CBCT acquisitions with or without the presence of MV scatter. This thesis explores the benefits of combining respiratory gating with IMRT/VMAT for the treatment of early stage NSCLC with SABR, and evaluates advanced on-board imaging capabilities to develop dose delivery verification protocols. The results of this thesis will provide the tools necessary to confidently implement a respiratory gated radiotherapy program aimed at improving the therapeutic ratio for early-stage NSCLC

SYNCHROTRON RADIATION INLINE PROPAGATION BASED PHASE CONTRAST COMPUTERIZED TOMOGRAPHY (PC-CT) OF HUMAN PROSTATE SAMPLE

The human prostate is an accessory male reproductive gland located below the neck of the urinary bladder. Benign prostatic hyperplasia (BPH) and prostate cancer are the frequently encountered pathological conditions of the prostate. It is estimated that 50% of men will develop BPH by age 50 with the incidence increasing to 90% by age 90. Prostate cancer is the second most common cause of cancer in men worldwide after lung cancer. In this study, we examined the ability of synchrotron radiation propagation phase-contrast computerized tomography (PC-CT) in comparison to ultrasound (US), magnetic resonance imaging (MRI) and histology, to characterize and differentiate various structural features and pathological lesions in 61 prostate tissues from 13 human patients collected during trans-urethral resection of the prostate. We compared the PC-CT, MRI, US and histology images of the same tissues from the same plane to determine if different structures like blood vessels, dilated acini etc. could be observed with each modality. The PC-CT was found to be a powerful imaging technique compared to MRI and US in identifying and resolving small structures located near each other. With PC-CT imaging, the same structures could be correctly identified almost 4 times and 15 times more often than MRI and US respectively. While comparing the ability to identify and resolve the nearby structures in PC-CT images reconstructed from 100%, 50% and 25% of the number of total projections collected (i.e. 2250 projections over 180 degree rotation of a sample on imaging stage), the ranking was as follows: 100% PC-CT>50% PC-CT>25% PC-CT (p<0.05). Radiation data recorded during a previous study while imaging dog cadavers with PC-CT were also analyzed. It was found that the average effective radiation dose imparted in a medium-sized dog during PC-CT imaging of one view of 7.8 mm height with 2000 projections in the biomedical imaging and therapy – insertion device (BMIT-ID) beamline of Canadian light source (CLS) beamline was 1,481.7 mSv, which is very high compared to the standard clinical CT examination deposits in human clinical medicine. The dose could be reduced by performing sparse view imaging i.e. 50% projection PC-CT or 25% projection PC-CT, but these amounts are still hazardous, such that a similar protocol used in human would have the potential to induce cancer later in life in approximately 0.5 % of the patients. For PC-CT imaging of human prostate in situ, a human positioning device was also designed. Due to the limitation in the weight-bearing capacity of the stage in the beamline, the positioning device was designed to be able to hold only a human pelvis or pelvis phantom up to 50 kg of weight in an upright position. The results from this work demonstrate that the synchrotron radiation-based inline PC-CT is a promising technique that offers closer-to-histology grade non-invasive diagnostic imaging of prostate tissue. Further study in conducting in-vivo prostate imaging to reduce the radiation dose is the next step to move forward in this direction