A novel receive-only liquid nitrogen (LN2)-cooled RF coil for high-resolution in vivo imaging on a 3-Tesla whole-body scanner

The design and operation of a receive-only liquid nitrogen (LN2)-cooled coil and cryostat suitable for medical imaging on a 3-T whole-body magnetic resonance scanner is presented. The coil size, optimized for murine imaging, was determined by using electromagnetic (EM) simulations. This process is therefore easier and more cost effective than building a range of coils. A nonmagnetic cryostat suitable for small-animal imaging was developed having good vacuum and cryogenic temperature performance. The LN2-cooled probe had an active detuning circuit allowing the use with the scanner's built-in body coil. External tuning and matching was adopted to allow for changes to the coil due to temperature and loading. The performance of the probe was evaluated by comparison of signal-to-noise ratio (SNR) with the same radio-frequency RF) coil operating at room temperature (RT). The performance of the RF coil at RT was also benchmarked against a commercial surface coil with a similar dimension to ensure a fair SNR comparison. The cryogenic coil achieved a 1.6- to twofold SNR gain for several different medical imaging applications: For mouse-brain imaging, a 100-mu m resolution was achieved in an imaging time of 3.5 min with an SNR of 25-40, revealing fine anatomical details unseen at lower resolutions for the same time. For heavier loading conditions, such as imaging of the hind legs and liver, the SNR enhancement was slightly reduced to 1.6-fold. The observed SNR was in good agreement with the expected SNR gain correlated with the loaded-quality factor of RF coils from the EM simulations. With the aid of this end-user-friendly and economically attractive cryogenic RF coil, the enhanced SNR available can be used to improve resolution or reduce the duration of individual scans in a number of biomedical applications

Doctor of Philosophy

dissertationThe spinal cord provides the major pathway for the signal transmission between the brain and peripheral nervous system. Any injury on the spinal cord may disrupt the signal transmission partially or completely, and lead to the permanent disability of the patient. Therefore, a technique which can evaluate the spinal cord disease burden and monitor the treatment progress noninvasively is very essential. Magnetic resonance imaging (MRI) has emerged as a powerful tool for imaging of the spinal cord because of its high soft-tissue contrast and specificity to the pathologic cord. However, using the conventional MRI methods such as T1-weighted and T2-weighted imaging, the disease burden and monitoring process cannot always be assessed accurately. An advanced imaging method, the diffusion MRI of spinal cord, has been proven as a more successful imaging method than the conventional MRI methods to detect the lesions in earliest stages; however, diffusion MRI of spinal cord is challenging. The major technical challenges for the high-resolution diffusion MRI of the spinal cord include the low signal-to-noise ratio (SNR) from the small cross-sectional area and deep location of the cord, large field inhomogeneity in the static magnetic field due to the magnetic susceptibility difference between tissue-bone interface, and patient’s involuntary as well as voluntary motions. In addition to the above technical challenges, the signal behavior and outcomes of the diffusion MRI cannot be easily interpreted in the spinal cord because of its complex microscopic structure. This dissertation contributes significantly in three areas to overcome the difficulties currently faced in diffusion MRI of the spinal cord. A Monte Carlo simulation (MCS) of water diffusion in white matter (WM) has been developed and performed. The simulation provides the deeper understanding of the signal measured in diffusion MRI, which facilitates easier interpretation of the outcomes of diffusion MRI. The results of the ultrahigh-b radial diffusion-weighted imaging (UHB-rDWI) of excised pig cervical spinal cord (CSC) agree fairly well with the results of the simulation. An improvement in the SNR of the spinal cord images was achieved by constructing an 8-channel CSC dedicated coil, which does not require a commonly used preamplifier decoupling technique to minimize the interaction between nonadjacent elements. The newly constructed coil provides 1.4âˆ'2 time SNR improvement compared with the manufacturer’s coil (Siemens’ head neck and spine matrix). A new sequence, 2D single-shot diffusion-weighted stimulated echo planar imaging with reduced field of view (2D ss-DWSTEPI-rFOV), has been developed for the UHB-rDWI of the spinal cord. The 2D ss-DWSTEPI-rFOV sequence acquires an image in a single excitation, and thereby reduces motion related artefacts. The reduced phase field of view imaging capability of the new sequence minimizes the off-resonance (field inhomogeneity and chemical shift) related artefacts. The time efficient sequence acquires stimulated echoes (STE) for the high-resolution UHB-rDWI of the spinal cord

Hyperpolarized 129Xe Magnetic Resonance Imaging of Radiation-Induced Lung Injury

Lung cancer is the largest contributor to cancer-related mortality worldwide. Only 20% of stage III non-small cell lung cancer patients survive after 5-years post radiation therapy (RT). Although RT is an important treatment modality for lung cancer, it is limited by Radiation-Induced Lung Injury (RILI). RILI develops in two phases: (i) the early phase (days-weeks) referred to radiation pneumonitis (RP), and (ii) the late phase (months). There is a strong interest in early detection of RP using imaging to improve outcomes of RT for lung cancer. This thesis describes a promising approach based on 129Xe gas as a contrast agent for Magnetic Resonance Imaging (MRI) of the lung airspace due to the large increase in signal possible by spin exchange optical pumping, or hyperpolarization (Hp). Additionally, 129Xe provides unique functional information due to its relatively high solubility and significant chemical shift in pulmonary tissue (PT) and red blood cell (RBC) compartments. In this thesis, a specialized Hp 129Xe MRI method was developed for detection of gas exchange abnormalities in the lungs associated with thoracic RT. In particular, the feasibility of quantifying the early phase of RILI is demonstrated in a rat model of RILI two weeks post-irradiation with a single fraction dose of 18 Gy. The challenge of low signal-to-noise ratio (SNR) in the dissolved phases was addressed in this work by development and construction of a Transmit-Only/Receive-Only radiofrequency coil. Another challenge addressed in the thesis was the lack of imaging techniques that provide sufficient spatial and temporal information for gas exchange. Therefore, a novel Hp 129Xe MRI technique was developed based on the multi-point IDEAL pulse sequence. The combination of these two developments enabled investigation of regional gas exchange changes associated with RP in the rat lung two weeks post-irradiation to assess the feasibility of early detection of RILI. Theoretical analysis of the gas exchange curves enabled measurements of average PT thickness (LPT) increases consistent with histology and relative blood volume (VRBC) reductions in the irradiated animal cohort compared to a non-irradiated cohort, and between irradiated right lungs compared to unirradiated left lungs in the irradiated cohort

Magnetic Resonance Imaging Studies of Angiogenesis and Stem Cell Implantations in Rodent Models of Cerebral Lesions

Molecular biology and stem cell research have had an immense impact on our understanding of neurological diseases, for which little or no therapeutic options exist today. Manipulation of the underlying disease-specific molecular and cellular events promises more efficient therapy. Angiogenesis, i.e. the regrowth of new vessels from an existing vascular network, has been identified as a key contributor for the progression of tumor and, more recently, for regeneration after stroke. Donation of stem cells has proved beneficial to treat cerebral lesions. However, before angiogenesis-targeted and stem cell therapies can safely be used in patients, underlying biological processes need to be better understood in animal models. Noninvasive imaging is essential in order to follow biological processes or stem cell fate in both space and time. We optimized steady state contrast enhanced magnetic resonance imaging (SSCE MRI) to monitor vascular changes in rodent models of tumor and stroke. A modification of mathematical modeling of MR signal from the vascular network allowed for the first time simultaneous measurements of relaxation time T2 and SSCE MRI derived blood volume, vessel size, and vessel density. Limitations of SSCE MRI in tissues with high blood volume and non-cylindrically shaped vessels were explored. SSCE MRI detected angiogenesis and response to anti-angiogenic treatment in two rodent tumor models. In both tumor models, reduction of blood volume in small vessels and a shift towards larger vessels was observed upon treatment. After stroke, decreased vessel density and increased vessel size was found, which was most pronounced one week after the infarct. This is in agreement with two initial, recently published clinical studies. Overall, very little signs of angiogenesis were found. Furthermore, superparamagnetic iron oxide (SPIO) labels were used to study neural stem cells (NSCs) in vivo with MRI. SPIO labeling revealed a decrease in volume of intracerebral grafts over 4 months, assessed by T2* weighted MRI. Since SPIO labels are challenging to quantify and their MR contrast can easily be confounded, we explored the potential of in vivo 19F MRI of 19F labeled NSCs. Hardware was developed for in vitro and in vivo 19F MRI. NSCs were labeled with little effect on cell function and in vivo detection limits were determined at ~10,000 cells within 1 h imaging time. A correction for the inhomogeneous magnetic field profile of surface coils was validated in vitro and applied for both sensitive and quantitative in vivo cell imaging. As external MRI labels do not provide information on NSC function we combined 19F MRI with bioluminescence imaging (BLI). The BLI signal allowed quantification of viable cells whereas 19F MRI provided graft location and density in 3D over 4 weeks both in the healthy and stroke brain. A massive decrease in number of viable cells was detected independent of the microenvironment. This indicates that functional recovery reported in many studies of NSC implantation after stroke, is rather due to release of factors by NSCs than direct tissue replacement. In light of these indirect effects, combination of the imaging methods developed in this dissertation with other functional and structural imaging methods is suggested in order to further elucidate interactions of NSCs with the vasculature

Recommendations and guidelines from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 1 -- In vivo small-animal imaging

The value of in vivo preclinical diffusion MRI (dMRI) is substantial. Small-animal dMRI has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. Many of the influential works in this field were first performed in small animals or ex vivo samples. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the data. This work aims to serve as a reference, presenting selected recommendations and guidelines from the diffusion community, on best practices for preclinical dMRI of in vivo animals. In each section, we also highlight areas for which no guidelines exist (and why), and where future work should focus. We first describe the value that small animal imaging adds to the field of dMRI, followed by general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss how they are appropriate for different studies. We then give guidelines for in vivo acquisition protocols, including decisions on hardware, animal preparation, imaging sequences and data processing, including pre-processing, model-fitting, and tractography. Finally, we provide an online resource which lists publicly available preclinical dMRI datasets and software packages, to promote responsible and reproducible research. An overarching goal herein is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.Comment: 69 pages, 6 figures, 1 tabl