Creation of 3D Digital Anthropomorphic Phantoms which Model Actual Patient Non-rigid Body Motion as Determined from MRI and Position Tracking Studies of Volunteers

Background: Patient motion during emission imaging can create artifacts in the reconstructed emission distributions, which may mislead the diagnosis. For example, in myocardial-perfusion imaging, these artifacts can be mistaken for defects. Various software and hardware approaches have been developed to detect and compensate for motion. There are various ways of testing the effectiveness of motion correction methods applied in emission tomography, including the use of realistic digital anthropomorphic phantoms. Purpose: The purpose of this study was to create 3D digital anthropomorphic phantoms based on MRI data of volunteers undergoing a series of clinically relevant motions. These phantoms with combined position tracking were used to investigate both imaging-data-driven and motion tracking strategies to estimate and correct for patient motion. Methods: MRI scans were obtained of volunteers undergoing a series of clinically relevant movements. During the MRI, the motions were recorded by near-infra-red cameras tracking using external markers on the chest and abdomen. Individual-specific extended cardiac-torso (XCAT) phantoms were created fit to our volunteer MRI imaging data representing pre- and post-motion states. These XCAT phantoms were then used to generate activity and attenuation distributions. Monte Carlo methods will then be performed to simulate SPECT acquisitions, which will be used to evaluate various motion estimation and correction strategies. Results: Three volunteers were scanned in the MRI with concurrent external motion tracking. Each volunteer performed five separate motions including an axial slide, roll, shoulder twist, spine bend, and arm motion. These MRI scans were then manually digitalized into 3D anthropomorphic XCAT phantoms. Activity and attenuation distributions were created for each XCAT phantom, representing fifteen individual-specific motions. Conclusions: Our results will be combined with the external motion tracking data to determine if external motion tracking accurately reflects heart position in patients undergoing cardiac SPECT imaging. This data will also be used to evaluate other motion correction methods in the future

Characterization and Compensation of Hysteretic Cardiac Respiratory Motion in Myocardial Perfusion Studies Through MRI Investigations

Respiratory motion causes artifacts and blurring of cardiac structures in reconstructed images of SPECT and PET cardiac studies. Hysteresis in respiratory motion causes the organs to move in distinct paths during inspiration and expiration. Current respiratory motion correction methods use a signal generated by tracking the motion of the abdomen during respiration to bin list- mode data as a function of the magnitude of this respiratory signal. They thereby fail to account for hysteretic motion. The goal of this research was to demonstrate the effects of hysteretic respiratory motion and the importance of its correction for different medical imaging techniques particularly SPECT and PET. This study describes a novel approach for detecting and correcting hysteresis in clinical SPECT and PET studies. From the combined use of MRI and a synchronized Visual Tracking System (VTS) in volunteers we developed hysteretic modeling using the Bouc-Wen model with inputs from measurements of both chest and abdomen respiratory motion. With the MRI determined heart motion as the truth in the volunteer studies we determined the Bouc Wen model could match the behavior over a range of hysteretic cycles. The proposed approach was validated through phantom simulations and applied to clinical SPECT studies

Non-invasive cardiac radiosurgery with MRI guidance: a ground-truth for real-time target localisation using the XCAT phantom

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. The growing epidemic of AF already affects millions of patients around the world and millions more are forecast to develop the condition in coming decades. The standard non-pharmacological treatment for AF is catheter ablation, an invasive and time consuming procedure. Non-invasive treatment of AF with radiosurgery has recently been put forward but is challenged by complex cardiac and respiratory motion. Compensating for target motion and treating in real-time could be realised with a MRI linear accelerator (MRI-Linac). A recent study developed methodology to track cardiac targets for this purpose but until now no measure of its accuracy has been accessible. In this investigation, the existing real-time cardiac tracking is quantified and developed on a digital phantom platform. It is first tested within a perfect digital scenario and then extended to a realistic anthropomorphic simulation. In a final experiment, developed tracking methods are applied to real-world anatomical data. A total number of twenty-one virtual patients were generated with the 4 dimensional extended cardiac-torso (XCAT) phantom software and received magnetic resonance imaging (MRI) simulated cardiac scans. A 3D volume representing a distinct cardiac phase is comprised of 2D slices which cover the entire target area. These template volumes are matched through pixel similarity to 2D orthogonal real-time MRI planes to localise the target volume in real-time. One virtual patient represented ideal and thus unrealistic MRI scans to initially test the cardiac tracking. Twenty virtual patients were subjected to MRI scans that closely model the proposed real-world scenario. An available ground-truth is compared to target motion trajectories output from the cardiac tracking algorithm for the twenty-one virtual patients. The cardiac tracking methodology is simultaneously developed as a result of the quantitative measures. Additionally, the correlation and significance of the virtual patients’ physiological parameters with tracking accuracy is investigated. Finally, the best performing tracking function is qualitatively assessed on a single patient’s real-world MRI scans. Employing a tracking method with the same basic methodology as the original tracking on the twenty virtual patient cohort resulted in a mean 3D tracking error of 3.2 ± 1.7 mm. The three anatomical plane constituent errors were 1.3 ± 0.9 mm in the superior inferior (SI) plane, 1.4 ± 0.9 mm in the anterior posterior (AP) plane and 2.2 ± 1.8 mm in the left right (LR) plane. This result is in strong agreement with the inferred error of 3 - 4 mm from the previous study that was based on 2D quantification. After tracking developments were implemented, the best performing mean 3D tracking error of 2.9 ± 1.6 mm was ascertained. A patient’s heart rate is the only anatomical parameter to show a significant linear relationship with tracking error (r=0.65, p-value = 0.0018). Comparing best performing tracking functions across the virtual patients show that the optimal tracking function is patient-specific. When the developed methods were reintroduced to a patient’s MRI data the tracking accuracy was qualitatively assessed to have improved. The results of the previous single patient treatment planning indicate that high-dose cardiac radiosurgery can be administered for the treatment of AF when safety margins are below 5 mm. The quantitative measures presented here demonstrate that real-time target localisation and motion compensation could successfully be implemented with an MRI-Linac. The conclusions of this work strongly encourage further development of the proposed AF treatment with non-invasive radiosurgery

MRI Contrast Agent Studies of Compartmental Differentiation, Dose-dependence, and Tumor Characterization in the Brain

Magnetic resonance imaging (MRI) has increasingly become the preferred imaging modality in modern day research to study disease. MRI presents an imaging technique that is practically non-invasive and without any ionizing radiation. This dissertation presents the use of contrast agents in MRI studies to differentiate compartments, to study dose dependence of relaxation times, and to characterize tumors using signal amplifying enzymes in the brain. Differentiating compartments in the brain can be useful in diffusion studies to detect stroke at an early stage. Diffusion-weighted NMR techniques have established that the apparent diffusion coefficient (ADC) of cerebral tissue water decreases during ischemia. However, it is unclear whether the ADC change occurs due to changes in the intracellular (IC) space, extracellular (EC) space, or both. To better understand the mechanism of water ADC changes in response to ischemic injury, making IC and EC compartment specific measurements of water diffusion is essential. The first study was done where manganese (Mn2+) was used as an IC contrast agent. Mn2+ uptake by cells causes shortening of the T1 relaxation time of IC water. The relative difference in T1 relaxation times between the IC and EC compartments can be used to discriminate between the MR signals arising from water in the respective compartments. Mn2+ is also widely used in manganese-enhanced MRI (MEMRI) studies to visualize functional neural tracts and anatomy in the brain in vivo. In animal studies, the goal is to use a dose of Mn2+ that will maximize the contrast while minimizing its toxic effects. The goal of dose study was to investigate the MRI dose response of Mn2+ in rat brain following SC administration of Mn2+. The dose dependence and temporal dynamics of Mn2+ after SC injection can prove useful for longitudinal in vivo studies that require brain enhancement to persist for a long period of time to visualize neuroarchitecture like in neurodegenerative disease studies. Contrast agents, in addition to their use in compartmental differentiation and dose studies, can be used for imaging tumors. The last study in this dissertation focuses on imaging EGF receptors in brain tumors. We tested a novel pretargeting imaging approach that includes the administration of humanized monoclonal antibody (anti-EGFR mAb, EMD72000) linked to enzymes with complementing activities that use a low-molecular weight paramagnetic molecule (diTyr-GdDTPA) as a reducing substrate administered following the mAb conjugates. We analyzed the differential MR tumor signal decay in vivo using orthotopic models of human glioma. The patterns of MR signal change following substrate administration revealed differences in elimination patterns that allowed distinguishing between non-specific and specific modes of MR signal decay

MRI Contrast Agent Studies of Compartmental Differentiation, Dose-Dependence, and Tumor Characterization in the Brain: A Dissertation

Magnetic resonance imaging (MRI) has increasingly become the preferred imaging modality in modern day research to study disease. MRI presents an imaging technique that is practically non-invasive and without any ionizing radiation. This dissertation presents the use of contrast agents in MRI studies to differentiate compartments, to study dose dependence of relaxation times, and to characterize tumors using signal amplifying enzymes in the brain. Differentiating compartments in the brain can be useful in diffusion studies to detect stroke at an early stage. Diffusion-weighted NMR techniques have established that the apparent diffusion coefficient (ADC) of cerebral tissue water decreases during ischemia. However, it is unclear whether the ADC change occurs due to changes in the intracellular (IC) space, extracellular (EC) space, or both. To better understand the mechanism of water ADC changes in response to ischemic injury, making IC and EC compartment specific measurements of water diffusion is essential. The first study was done where manganese (Mn2+) was used as an IC contrast agent. Mn2+ uptake by cells causes shortening of the T1 relaxation time of IC water. The relative difference in T1 relaxation times between the IC and EC compartments can be used to discriminate between the MR signals arising from water in the respective compartments. Mn2+ is also widely used in manganese-enhanced MRI (MEMRI) studies to visualize functional neural tracts and anatomy in the brain in vivo. In animal studies, the goal is to use a dose of Mn2+ that will maximize the contrast while minimizing its toxic effects. The goal of dose study was to investigate the MRI dose response of Mn2+ in rat brain following SC administration of Mn2+. The dose dependence and temporal dynamics of Mn2+ after SC injection can prove useful for longitudinal in vivo studies that require brain enhancement to persist for a long period of time to visualize neuroarchitecture like in neurodegenerative disease studies. Contrast agents, in addition to their use in compartmental differentiation and dose studies, can be used for imaging tumors. The last study in this dissertation focuses on imaging EGF receptors in brain tumors. We tested a novel pretargeting imaging approach that includes the administration of humanized monoclonal antibody (anti-EGFR mAb, EMD72000) linked to enzymes with complementing activities that use a low-molecular weight paramagnetic molecule (diTyr-GdDTPA) as a reducing substrate administered following the mAb conjugates. We analyzed the differential MR tumor signal decay in vivo using orthotopic models of human glioma. The patterns of MR signal change following substrate administration revealed differences in elimination patterns that allowed distinguishing between non-specific and specific modes of MR signal decay

Clinical Validation of an Optical Surface Detection System for Stereotactic Radiosurgery with Frameless Immobilization Device in CNS Tumors

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Radiações em Diagnóstico e Terapia), 2022Stereotactic Radiosurgery (SRS) has been consolidated in recent years as the treatment of choice in selected central nervous system (CNS) tumors. With the introduction of stereotactic approach in clinical practice, accurate immobilization and motion control during treatment becomes fundamental. During SRS treatments, the common practice is to immobilize CNS patients in a cushion molded head support, with specific open-face thermoplastic masks. To verify and correct internal isocenter uncertainties before and during treatment, X-Ray volumetric imaging (XVI) is performed - image guided radiation therapy (IGRT). An alternative to mid‐treatment imaging is optical surface detection (OSD) imaging – a non‐invasive, non‐radiographic form of image guidance – to monitor patient intra-fraction motion. This imaging technique has shown to properly position, accurately monitor, and quantify patient movements throughout the entirety of the treatment – surface guided radiation therapy (SGRT). The aim of this investigation is to test the viability of the implementation of a maskless immobilization approach, using only a vacuum mouthpiece suction system for head fixation in patients with CNS tumors who will undergo SRS treatment under the guidance of an OSD system coupled with 6-Degree of Freedom (6-DOF) robotic couch for submillimeter position correction. This master thesis addresses the five technical performance tests conducted on the Linear Accelerator components – XVI, HexaPOD couch and OSD system in the Radiotherapy Department of Hospital CUF Descobertas. The results obtained lecture the best acquisition orientation to perform image verification; if the HexaPOD couch is correctly calibrated to the XVI radiation isocenter to assure submillimeter corrections; OSD system performance regarding phantom surface detection since some immobilization components can block the signal reading; which coplanar and non-coplanar angles occur most signal inconsistencies due to camera pod occlusion; what is the overall OSD system accuracy and what is the best non-coplanar angle arrangement to perform an SRS treatment with OSD system monitoring

Automated Deformable Mapping Methods to Relate Corresponding Lesions in 3D X-ray and 3D Ultrasound Breast Images

Mammography is the current standard imaging method for detecting breast cancer by using x-rays to produce 2D images of the breast. However, with mammography alone there is difficulty determining whether a lesion is benign or malignant and reduced sensitivity to detecting lesions in dense breasts. Ultrasound imaging used in conjunction with mammography has shown valuable contributions for lesion characterization by differentiating between solid and cystic lesions. Conventional breast ultrasound has high false positive rates; however, it has shown improved abilities to detect lesions in dense breasts. Breast ultrasound is typically performed freehand to produce anterior-to-posterior 2D images in a different geometry (supine) than mammography (upright). This difference in geometries is likely responsible for the finding that at least 10% of the time lesions found in the ultrasound images do not correspond with lesions found in mammograms. To solve this problem additional imaging techniques must be investigated to aid a radiologist in identifying corresponding lesions in the two modalities to ensure early detection of a potential cancer. This dissertation describes and validates automated deformable mapping methods to register and relate corresponding lesions between multi-modality images acquired using 3D mammography (Digital Breast Tomosynthesis (DBT) and dedicated breast Computed Tomography (bCT)) and 3D ultrasound (Automated Breast Ultrasound (ABUS)). The methodology involves the use of finite element modeling and analysis to simulate the differences in compression and breast orientation to better align lesions acquired from images from these modalities. Preliminary studies were performed using several multimodality compressible breast phantoms to determine breast lesion registrations between: i) cranio-caudal (CC) and mediolateral oblique (MLO) DBT views and ABUS, ii) simulated bCT and DBT (CC and MLO views), and iii) simulated bCT and ABUS. Distances between the centers of masses, dCOM, of corresponding lesions were used to assess the deformable mapping method. These phantom studies showed the potential to apply this technique for real breast lesions with mean dCOM registration values as low as 4.9 ± 2.4 mm for DBT (CC view) mapped to ABUS, 9.3 ± 2.8 mm for DBT (MLO view) mapped to ABUS, 4.8 ± 2.4 mm for bCT mapped to ABUS, 5.0 ± 2.2 mm for bCT mapped to DBT (CC view), and 4.7 ± 2.5 mm for bCT mapped to DBT (MLO view). All of the phantom studies showed that using external fiducial markers helped improve the registration capability of the deformable mapping algorithm. An IRB-approved proof-of-concept study was performed with patient volunteers to validate the deformable registration method on 5 patient datasets with a total of up to 7 lesions for DBT (CC and MLO views) to ABUS registration. Resulting dCOM’s using the deformable method showed statistically significant improvements over rigid registration techniques with a mean dCOM of 11.6 ± 5.3 mm for DBT (CC view) mapped to ABUS and a mean dCOM of 12.3 ± 4.8 mm for DBT (MLO view) mapped to ABUS. The present work demonstrates the potential for using deformable registration techniques to relate corresponding lesions in 3D x-ray and 3D ultrasound images. This methodology should improve a radiologists’ characterization of breast lesions which can reduce patient callbacks, misdiagnoses, additional patient dose and unnecessary biopsies. Additionally, this technique can save a radiologist time in navigating 3D image volumes and the one-to-one lesion correspondence between modalities can aid in the early detection of breast malignancies.PHDNuclear Engineering & Radiological SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/150042/1/canngree_1.pd