Browsing by Author "Darnell, Dean"

Alzheimer's disease (AD) accounts for 60%-80% of dementia. AD patients start by having mild memory, language, and thinking difficulties, then gradually lose more critical abilities, such as dressing, bathing, or walking. AD not only degrades patients’ life quality but also burdens caregivers and the health system. Specifically, there are 6.5 million AD cases in the U.S. today, and the annual health costs for 2022 are estimated to be $321 billion. AD diagnosis has been evolving in the past 30 years. The criteria established in 1984 recommended that AD cannot be identified until a post-mortem neuropathological test is performed. Recently, more biomarkers have gradually been discovered, such as brain atrophy, Positron Emission Tomography (PET) measures of glucose hypometabolism, and cerebrospinal fluid (CSF) and PET measures of pathological amyloid-beta and tau. However, these biomarkers lack the specificity to probe the damage in the neuronal microstructure that directly causes the disease, and they only provide late diagnoses when the AD progression is no longer reversible. Since the neuronal damages are believed to begin 20 years or more before symptoms start, biomarkers that can detect abnormalities in the neuronal microstructure would enable the diagnosis of AD at the very early stage of neurodegeneration, years before the onset of symptoms, and they could thus potentially enable better treatment outcomes since neuronal damage at the early stage could be reversible.Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that can noninvasively probe the microstructure of the human brain in vivo. Some regions in the cortical gray matter and hippocampus are known to experience early neurodegeneration in AD, and changes in DTI metrics in these regions could reflect the early stage of AD. However, the cortex is folded and is made of different cortical layers and cortical regions and the hippocampus is made of different subfields that have distinct neuronal populations with a specific microstructure. Additionally, neurodegeneration does not necessarily occur at the same time across different cortical depths or regions in the cortex or across different subfields in the hippocampus. As such, the development of early diagnostic biomarkers would require the ability to probe the neuronal microstructure at specific cortical depths and in specific cortical regions and hippocampal subfields in vivo. However, doing so with DTI has been challenging because the average cortical thickness is only 2.5 mm and the average hippocampal volume is only 2.84 mL. Therefore, a high-resolution DTI acquisition within a reasonable scan time is needed. In this dissertation, we first aim to develop DTI acquisition and reconstruction methodologies to acquire high-resolution (0.9-mm to 1.0-mm isotropic) whole-brain DTI images. Specifically, we used an efficient multi-band multi-shot echo-planar imaging sequence and a multi-band multiplexed sensitivity-encoding reconstruction. Furthermore, we aim to develop a data analysis pipeline that can quantitatively probe the microstructure and capture characteristic features: 1) in the cortex by performing a column-based cortical depth analysis of the diffusion anisotropy and radiality; and 2) in the hippocampus by investigating intra-hippocampal fiber tracts and connectomes, with the long-term goal of enabling the early diagnosis of AD. In the cortex, a column-based cortical depth analysis that samples the fractional anisotropy (FA) and radiality index (RI) along radially oriented cortical columns was performed to quantitatively analyze the FA and RI dependence on the cortical depth, cortical region, cortical curvature, and cortical thickness across the whole brain. We first studied young healthy subjects to optimize the data acquisition and analysis pipeline and to investigate the consistency of the results. The results showed characteristic FA and RI vs. cortical depth profiles, with an FA local maximum and minimum (or two inflection points) and a single RI maximum at intermediate cortical depths in most cortical regions, except for the postcentral gyrus where no FA peaks and a lower RI were observed. These results were consistent between repeated scans from the same subjects and across different subjects. They were also dependent on the cortical curvature and cortical thickness in that the characteristic FA and RI peaks were more pronounced i) at the banks than at the crown of gyri or at the fundus of sulci and ii) as the cortical thickness increases. We then performed a preliminary clinical study in a small cohort of AD patients and age-matched healthy controls (HC) to further examine if this methodology could be applied to detect differences in the FA and RI vs. cortical depth profiles between the AD and HC groups. The FA and RI at each cortical depth and in different regions of interest (ROIs) were sampled and compared between these two groups to look for any significant differences. Additionally, based on the results from the young healthy subjects, we minimized the dependence of these DTI metrics (FA and RI) on structural metrics such as cortical thickness and cortical curvature. The results showed significant differences (p < 0.05) in the FA and RI profiles between the AD and HC groups for specific cortical depths, curvature subsets, and ROIs. To generate intra-hippocampal fiber tracts and connectomes, the hippocampus of all subjects was registered to a common template and deterministic fiber tracking was performed. The fiber orientations across hippocampal subfields were investigated, and the connectivity among subfields was quantified. The results showed characteristic fiber orientations in different hippocampal subfields that were generally consistent between repeated scans and across all subjects: right/left in the middle of the CA4/dentate gyrus subfield and the inferior part of the subiculum; anterior/posterior in CA2/CA3; superior/inferior in the medial and inferior parts of the molecular layer and subiculum. These in vivo fiber orientations aligned with those obtained from an ex vivo specimen scanned over 21 hours at a 0.2-mm isotropic resolution. However, the ex vivo scan delineated the C-shaped molecular layer, which was not shown in the in vivo scans. The in vivo connectomes were generally consistent between repeated scans and across all subjects. The in vivo and ex vivo connectomes both showed more connectivity within the head than within the body of the hippocampus; however, the in vivo and ex vivo connectivity ranking across pairs of subfields was not exactly the same, which could be explained by altered diffusion properties in the ex vivo sample due to fixation or by the higher resolution in the ex vivo scan. In conclusion, the proposed high-resolution whole-brain DTI acquisition, column-based cortical depth analysis of the diffusion anisotropy and radiality, and intra-hippocampal fiber tracking captured characteristic features of FA and RI vs. cortical depth profiles in the cortex and characteristic fiber orientations and connectivity strengths across different subfields of the hippocampus, which were consistent between repeated scans from the same subjects and across different subjects. In addition, the cortical analysis applied in a preliminary clinical study of AD patients vs. HC showed significant differences in the FA and RI profiles between these two groups, showing the potential of this methodology to generate biomarkers for the early diagnosis of AD.

Project 1 (Chapter 2): Dose Verification andMonte Carlo Modeling of an Image-GuidedSmall Animal Radiotherapy Irradiator

Purpose: Preclinical trials play a crucial role in advancing the understanding of cancer biology and developing effective therapeutic interventions. The purpose of this project is to simulate and validate beam output of a Small Animal Radiotherapy Research Platform (SARRP, xStrahl) with both physical dosimetry and Monte Carlo simulation models.

Materials and Methods: The SARRP console was set up to deliver an intended dose of 8Gy (4 Gy anterior-posteriorly (AP), 4 Gy posterior-anteriorly (PA)) in 142 seconds to a flat mouse phantom. The x-ray irradiation parameters were set to 13 mA, 220 kVp, with a 33.725 cm source to surface distance. Beam filtration included 0.8 mm Be (inherent) and 0.15 mm Cu (added), with collimation set to 40x30 mm. Dose verification was conducted through two methods: utilizing an energy-calibrated MOSFET dosimeter and employing Monte Carlo Simulations using Monte Carlo N- Particle Transport (MCNP). MOSFET Calibration encompassed four setups to ensure precision. The first two involved calibrating the MOSFET with an ion chamber in air at 0 degrees (Setup 1) and 180 degrees (Setup 2). The subsequent two setups calibrated the MOSFET positioned inside the phantom (Setups 3 and 4) with an ion chamber in air. After the calibrations, the MOSFET, placed inside the phantom, received the intended 4 Gy dose for verification. The MCNP simulation comprised two stages: a point source simulation and a simulation of the x-ray tube. For the point source, the SARRP geometry was replicated, with the x-ray tube modeled as a collimated point source. The x-ray tube simulation entailed modeling components of the xray tube. Validation methods included comparing energy spectra, Half Value Layer (HVL) testing, and film analysis of the anode heel effect.

Results: In the dose verification, Setup 1 exceeds the intended 4 Gy dose by 7.72%, while Setup 2 underdoses by 2.96%, resulting in a cumulative overdose of 2.38% for Setups 1 and 2. Setup 3 aligns with the intended 4 Gy dose, underdosing slightly by 0.14%, while Setup 4 underdoses by 2.31%. The cumulative dose for Setups 3 and 4 totals 7.90 Gy, indicating a 1.27% underdose. The two calibration techniques demonstrate a difference of 3.6%. Calibration in air is the preferred method due to the ionization chamber also being present in air. Point Source Simulation yielded doses of (4.27 ± 0.02) Gy (AP) and(3.77 ± 0.02) Gy (PA). X-ray Tube Simulation resulted in (3.95 ± 0.02) Gy (AP). Energy spectrum of the MCNP model showed good agreement with the manufacturer model in key spectral characteristics (peaks, mean energies). HVL comparison showed good agreement with only a 0.5% difference between simulated and experimental half value thicknesses. The anode-heel effect analysis was inconclusive.

Conclusions: The dose verification processes establish the SARRP’s efficacy in delivering the intended radiation dose. The integration of advanced measurement techniques set a benchmark for small animal dosimetry and ultimately strengthens the reliability of radiation doses in preclinical studies.

Project 2 (Chapter 3): Investigation of Occupational Radiation Exposure to InterventionalRadiologists from Use of Fluoroscopic Imaging

Purpose: The purpose of this project is to investigate radiation exposure among Interventional Radiology (IR) physicians using fluoroscopic imaging through experimental data collection and retrospective analysis, with objectives to understand Automatic Exposure Rate Control mechanisms, assess exposure rates to operators, and identify trends amongIR physicians.

Materials and Methods: Three interventional fluoroscopes were investigated: Philips AlluraClarity Xper FD 20/15, Philips Allura Xper FD20, and GE Discovery IGS 740. Two phantoms were employed to replicate patient and operator. The “patient” phantom was comprised of water-equivalent slabs (5cm thick, 30cm x 30cm). The “operator” phantom (Atom Dosimetry Labs Adult Male phantom) was placed beside the table and covered with a 0.25 mm lead apron. A Ludlum 9DP pressurized ion chamber was positioned at collar level of the operator phantom. Parameters varied included patient thickness (20cm-40cm), collimation, and fluoroscopy and acquisition modes. Exposure (mR) to “operator”were measured and normalized to number of x-ray pulses. Retrospective analysis used Radiation Dose Structured Report data for an 8-month period. Physician caseload, averageCumulative Air Kerma (CAK) by physician, and total CAK by physician were determined.

Results: Based on measured data, acquisition mode exhibits longer pulse widths (7.20x-31.3x) and higher tube current (1.48x-7.58x) compared to fluoroscopy for all units. Tube voltage increases with phantom thickness in both fluoroscopy and acquisition mode for all units. Increasing phantom size and collimated field size elevate the operator exposure rate for all C-arms. Larger field sizes contribute to higher exposure rates compared to small field sizes (4.91x-6.27x fluoroscopy, 5.51x-8.23x acquisition). Additionally, acquisition mode contributes to higher exposure rates (23.4x–107.1x) than fluoroscopy. Analysis of proceduraldata identified trends in case distribution and dose to patients across physicians.

Conclusions: Overall, patient size, collimation settings, and fluoroscopy vs. acquisition mode were identified as significant contributors to operator exposure rates. Outliers among IR physicians highlighted the need for targeted interventions to mitigate excessive radiation exposure.

Magnetic Resonance Imaging (MRI) image quality is strongly dependent on the homogeneity of the main magnetic field, B0. Inhomogeneities in this magnetic field lead to image artifacts such as: blurring, signal loss, and gross distortions of the imaged anatomy of the brain, degrading the images effectiveness to provide diagnostic information. A new radio-frequency (RF) head coil design with integrated direct-current (DC) shim coils to provide localized B0 shimming of the brain and simultaneously provide parallel excitation of reception is presented in this thesis. This design optimizes both the RF and DC shim coils proximity to the subject thereby maximizing both the signal-to-noise ratio and the shimming efficiency. This coil architecture is termed iPRES (integrated parallel receive, excitation and shimming).

An existing 32 channel receive-only head coil array was modified into an iPRES coil architecture. The coils of the array were modified using RF components to enable the simultaneous flow of both RF and DC currents on the same structure. The RF and DC currents provide concurrent signal reception and localized B0 shimming to the brain, respectively. In this thesis, the techniques, measurements and quality-metrics used to facilitate the iPRES coil array modification will be discussed.

The localized B0 shimming performance is evaluated in the frontal region of the brain which suffers from large susceptibility artifacts at the air/tissue boundary of the brain and the sinus. Axial B0 maps and echo-planar images (EPI) are acquired in vivo with optimized DC shim currents demonstrating a reduction in B0 inhomogeneities in the frontal lobe resulting in improved image EPI image quality. The coils quality factor and signal-to-noise ratio did not suffer as a result of the coil modification. The shimming performance and RF quality metrics are compared to standard whole-body spherical harmonic shimming and are discussed at length in the following chapters.

Finally, initial phantom results from the next-generation iPRES coil array will be presented. This architecture again uses an existing RF head coil array to simultaneously drive RF currents for reception and DC currents for local shimming. However, the shimming is further enhanced by providing additional RF-isolated shim coils which increases the shimming degrees of freedom. This design is useful when fast-changing, asymmetric B0 inhomogeneities are present in the imaged anatomy.

Magnetic resonance imaging (MRI) systems rely on wired radio-frequency (RF) coil arrays placed near the anatomical region of interest to acquire images. However, these wired arrays have a long setup time and RF currents induced on their cables can potentially burn nearby tissue. A novel coil design, termed an integrated RF/wireless (iRFW) coil, eliminates these issues by removing the cabled connection between the coil array and the scanner. In lieu of transmitting the acquired signal through wired connections, the iRFW coil transmits data wirelessly over the air at a WiFi frequency (2.442 GHz).Previous work has shown that the iRFW coil can be used for low data rate applications (e.g., ~10 Megabytes/sec), but further investigation at higher data rates (~300 Megabytes/sec) is needed in order to adequately transfer acquired MR image data. Electromagnetic simulations are performed in this study to computationally determine the optimal iRFW coil size and position in the MRI scanner bore. The simulations determine: 1. The similarity in MR signal-to-noise ratio between a traditional RF coil and an iRFW coil, 2. The amount of localized heating in a human subject’s body due to the transmitted wireless signal, 3. The strength of the wireless data transmission between the iRFW coil inside the scanner bore and connecting antennas outside the bore for different coil sizes and positions, and 4. The stability of the wireless transmission link for the optimal coil size and position with different subject body lengths. The optimal coil size and position are determined by considering the trade-off between reducing localized heating in human subject tissue and maximizing the transmission link between the iRFW coil and adjacent antennas. Completed simulations indicate that specific coil sizes and positions do result in an improved connection. In future work, these simulations will be validated by a physical model.

A novel integrated RF/wireless coil design, termed an integrated RF/wireless coil, which enables simultaneous MR image acquisition and wireless data transfer, has recently been proposed. The integrated RF/wireless coil design allows radio-frequency (RF) currents to flow on the coil simultaneously at the Larmor frequency, for MR image acquisition, and at the 2.4 GHz wireless communication frequency, for wireless data transfer from within the MRI scanner bore to a wireless Access Point (AP) on the scanner room wall. The integrated RF/wireless coil design provides a low-cost solution for wireless data transmission between the scanner bore and the console room that requires no mechanical modifications to the existing MRI system, which can 1) reduce the need for cumbersome cabling networks in the scanner, 2) increase patient comfort, and 3) decrease patient set up time.

In previous work, the radiated energy emitted from the integrated RF/wireless coil was not optimized for wireless data transfer between the coil in the scanner bore and the AP on the scanner room wall. The wireless data transfer from an integrated RF/wireless coil is optimal when the maximum amount of radiated power in the wireless communication band is transferred from the integrated RF/wireless coil to the AP, and the power deposited into the subject in the scanner is minimized. However, measurements of the radiated power from the integrated RF/wireless coil in the MRI environment (i.e., in the scanner bore and on a human) are not practical because they would require an excessively large anechoic chamber. Thus, electromagnetic simulations are performed to determine the optimal integrated RF/wireless coil design (e.g., size, position on the subject) that maximizes the radiated power delivered from the coil to an AP while 1) ensuring no degradation in SNR compared to a traditional RF coil and 2) minimizing the radiated power deposited into the subject in the scanner bore.

In this work, 3-D finite element electromagnetic co-simulations with an RF circuit designer are performed to optimize the gain of an integrated RF/wireless coil on a human phantom in the scanner bore and the corresponding S21 power transmission (i.e., link budget) between the coil and an AP on the scanner room wall. These simulations are verified by constructing an integrated RF/wireless coil and by using it to perform free-space radiated gain pattern measurements in an anechoic chamber and to acquire SNR maps of a uniform water phantom in an MRI scanner.

In the reconstruction of magnetic resonance (MR) images, two important assumptions that are made are that the main magnetic field B_0 is homogeneous and that there is no bulk movement of the subject. This work proposes various strategies using innovations in radio-frequency (RF) coil design to address the problems that arise when these assumptions are broken.

Typically, B_0 inhomogeneities are caused by susceptibility differences at air/tissue interfaces and result in image artifacts such as geometric distortions and signal loss. B_0 inhomogeneities can be corrected through a process called shimming, which generates magnetic field patterns that have a similar spatial distribution but are opposite in polarity. 2\nd order spherical harmonic shimming is used on most clinical scanners, however, it is unable to correct highly localized \B_0 inhomogeneities found in the inferior frontal and temporal brain regions. By integrating a direct current (DC) path onto an RF surface coil, thereby allowing both DC current and an RF current at the Larmor frequency to flow on the same coil, localized B_0 shimming and MR imaging can be performed with the same coil array. This technology, referred to as an integrated parallel reception, excitation, and shimming (iPRES) coil array, was previously used to correct for distortions in spin-echo echo-planar imaging (EPI) and is further developed here to also recover signal loss in gradient-echo EPI, which is used for blood-oxygenation level-dependent (BOLD) functional MRI (fMRI). This was done through modification of the cost function used in the shim optimization, which typically uses a single term representing the B_0 inhomogeneity, to include a second term representing the signal loss, with an adjustable weight to optimize the trade-off between distortion correction and signal recovery. Simulations and experiments were performed to investigate the shimming performance. Slice-optimized shimming with iPRES and the proposed cost function substantially reduced the signal loss in the inferior frontal and temporal brain regions compared to shimming with iPRES and the original cost function or 2nd-order spherical harmonic shimming with either cost function. In breath-holding BOLD fMRI experiments, the ∆B_0 and signal loss root-mean-square errors decreased by -34.3% and -56.2%, whereas the EPI signal intensity and number of activated voxels increased by 60.3% and 174.0% in the inferior frontal brain region.

In addition to the integration of DC currents, currents at a Wi-Fi frequency can be integrated onto RF coils as well to perform simultaneous MR imaging and wireless communication. This technology, called an integrated RF/wireless (iRFW) coil, has previously been used for wireless respiratory monitoring with a respiratory belt or to wirelessly control shim currents, and is further developed here to wirelessly transmit ultrasound data acquired with an organ-configuration motion (OCM) sensor. OCM sensors are small, ultrasound based sensors that attach to the skin, move with the subject, and provide information about internal physiological motion. They can be used to create synthesized MR images through machine learning techniques and to monitor patient motion, and ultimately can be used to improve various treatments and therapies. However, they currently require electronics that must remain outside of the scanner as well as various wired connections to those electronics, which limits their portability. By making the OCM sensors wireless and their associated electronics MR-compatible, setup time is decreased and the OCM sensor can accompany the patient throughout the hospital while monitoring motion. This was done by developing MR-compatible, battery-powered electronics to trigger the ultrasound sensor, digitize the received ultrasound signal, modulate it to a Wi-Fi frequency, and wirelessly transmit it via the iRFW coil to a nearby access point (AP). Phantom experiments were performed to ensure that 1) the MR data quality was unaffected with and without wirelessly transmitting ultrasound data and that 2) the ultrasound data was unaffected with and without acquiring MR images. In vivo experiments were performed to demonstrate the portability of the wireless ultrasound device and its ability to monitor motion.

AbstractPurpose: Integration of wireless data transfer in magnetic resonance imaging (MRI) would allow for the reduction of wired connections between the scanner subsystems and the control computers located outside the scanner room, which add to the cost and complexity of the scanner, reduce patient comfort, and impede the application of next-generation MRI technologies.

Methods:In this dissertation, a novel RF coil design, termed the wireless integrated parallel reception, excitation, and shimming (iPRES-W) coil design, is further developed to remove some of these wired connections by offering a compact and easy-to-integrate MR-compatible wireless data transfer solution, which requires no scanner modifications or additional antenna systems in the bore. The iPRES-W coil design allows both a direct current (DC) and radio-frequency (RF) currents at the Larmor frequency and in a wireless communication band to flow on the same coil element to enable simultaneous MR image acquisition and wireless data transfer, which enables: wireless localized B0 shimming; wireless peripheral system data transfer to augment imaging (e.g., respiratory tracking using a respiratory belt); wireless transfer of the scanner control signal to control on-coil electronics (e.g., Q-spoiling); and wireless power harvesting to power components of the iPRES-W system. To demonstrate the performance and utility of the iPRES-W coil design in clinically relevant applications, this dissertation has four aims: 1. To develop an iPRES-W spine coil array to perform simultaneous MR imaging and wireless localized B0 shimming of the spinal cord; 2. To develop a dual-stream iPRES-W head coil array for simultaneous MR imaging of the brain and multiple wireless data streams for control of separate peripheral systems, specifically, wireless localized B0 shimming and respiratory tracking using a respiratory belt; 3. To further develop an integrated RF/wireless coil design for wireless transfer of the scanner trigger signal to perform the Q-spoiling required for MR image acquisition; 4. To design a wireless power harvesting system to convert the high-energy RF energy emitted by the scanner during the transmit cycle into a DC voltage to charge the batteries to power in-bore electronics and B0 shim currents.

Results:The results from this dissertation demonstrate that the iPRES-W coil modifications did not degrade the signal-to-noise ratio (SNR) when implemented onto different radio-frequency coil structures (e.g., a conventional RF coil element and novel adaptive imaging receive (AIRTM) coil element). Wireless localized B0 shimming with the iPRES-W spine array and dual-stream iPRES-W head coil array substantially reduced the B0 root-mean-square-error (RMSE) by 70.1% and -41.2% in the spinal cord and frontal brain region, which corresponded to reduced DTI and EPI distortions, respectively. The wireless performance of the iPRES-W and iRFW coil elements measured in an anechoic chamber were minimally impacted by the introduction of a saline phantom representing tissue or during wireless Q-spoiling, respectively. The power harvesting experiments performed showed that the 4-channel power harvesting coil array could convert RF energy from the scanner into a DC voltage for recharging MR-compatible batteries for various scan parameters and imaging sequences.

Conclusions:The iPRES-W and iRFW coil designs can be integrated into different coil structures and arrays to perform simultaneous imaging, wireless localized B0 shimming, and wireless transfer of peripheral device data (e.g., respiratory tracking with a respiratory belt), with no SNR degradation, minimal change in wireless performance, and without scanner modifications or additional antenna systems within the scanner bore. Additionally, the power harvesting array can supply wireless power to charge MR-compatible batteries for various scan types and parameters.

MRI has emerged as a promising modality for detecting, staging, and monitoring treatment of prostate cancer in patients. Often prostate MRI exams make use of the endorectal coil (ERC) to improve the SNR on the prostate. However, it the ERC has limitations. The ERC is uncomfortable for patients and technicians, takes up hour time slots while non-ERC exams take up thirty-minute slots, and adds expense as every ERC is single use. Therefore, to increase patient quality of exam and hospital efficiency, this thesis endeavors to evaluate the use of ERC as a function of body habitus. Variability of patient weight, thickness, circumference, and BMI were evaluated against coil SNR to determine which body habitus threshold offering greatest SNR. Findings showed that using an A/P thickness threshold of 25 cm or patient circumference of 105 cm potentially offers acceptable SNR while removing use of ERC, but further testing is required.