Browsing by Subject "Magnetic Resonance Imaging (MRI)"

Mice have become the preferred model system for studying brain function and disease. With the powerful genetic tools available, mouse models can be created to study the underlying molecular basis of neurobiology in vivo. Just as magnetic resonance imaging is the dominant tool for evaluating the human brain, high-resolution MRI--magnetic resonance microscopy (MRM)--is a useful tool for studying the brain of mouse models. However, the need for high spatial resolution limits the signal-to-noise ratio (SNR) of the MRM images. To address this problem, T1-shortening contrast agents can be used, which not only improve the tissue contrast-to-noise ratio (CNR) but also increase SNR by allowing the MR signal to recover faster between pulses. By "actively staining" the tissue with these T1-shortening agents, MRM can be performed with higher resolution, greater contrast, and shorter scan times. In this work, active staining with T1-shortening agents was used to enhance three types of in vivo mouse brain MRM: (1) angiographic imaging of the neurovasculature, (2) anatomical imaging of the brain parenchyma, and (3) functional imaging of neuronal activity.

For magnetic resonance angiography (MRA) of the mouse, typical contrast agents are not useful because they are quickly cleared by the body and/or extravasate from the blood pool before a high-resolution image can be acquired. To address these limitations, a novel contrast agent--SC-Gd liposomes--has been developed, which is cleared slowly by the body and is too large to extravasate from the blood pool. In this work, MRA protocols were optimized for both the standard technique (time-of-flight contrast) and SC-Gd liposomes. When the blood was stained with SC-Gd liposomes, small vessel CNR improved to 250% that of time-of-flight. The SC-Gd liposomes could also be used to reduce scan time by 75% while still improving CNR by 32%.

For MRM of the mouse brain parenchyma, active staining has been used to make dramatic improvements in the imaging of ex vivo specimens. However for in vivo imaging, the blood-brain barrier (BBB) prevents T1-shortening agents from entering the brain parenchyma. In this work, a noninvasive technique was developed for BBB opening with microbubbles and ultrasound (BOMUS). Using BOMUS, the parenchyma of the brain could be actively stained with the T1-shortening contrast agent, Gd-DTPA, and MRM images could be acquired in vivo with unprecedented resolution (52 x 52 x 100 micrometers3) in less than 1 hour.

Functional MRI (fMRI), which uses blood oxygen level dependant (BOLD) contrast to detect neuronal activity, has been a revolutionary technique for studying brain function in humans. However, in mice, BOLD contrast has been difficult to detect and thus routine fMRI in mice has not been feasible. An alternative approach for detecting neuronal activity uses manganese (Mn2+). Mn2+ is a T1-shortening agent that can enter depolarized neurons via calcium channels. Thus, Mn2+ is a functional contrast agent with affinity for active neurons. In this work, Mn2+ (administered with the BOMUS technique) was used to map the neuronal response to stimulation of the vibrissae. The resultant activation map showed close agreement to published maps of the posterior-lateral and anterior-medial barrel field of the primary sensory cortex.

The use of T1-shortening agents to actively stain tissues of interest--blood, brain parenchyma, or active neurons--will facilitate the use of MRM for studying mouse models of brain development, function, and disease.

It is possible to investigate in vivo musculoskeletal biomechanics using multimodal medical imaging techniques; however, the analysis of medical image sets is often time-prohibitive. In this dissertation, I outline various projects that utilize magnetic resonance imaging (MRI) scans acquired before and after exercise to quantify cartilage thickness changes incurred by the loading activity. A better understanding of cartilage mechanics is crucial for prediction and prevention efforts related to osteoarthritis, patellofemoral pain, and other musculoskeletal conditions. While this cartilage "stress test'' protocol has been used in the past to investigate knee, ankle, and spine mechanics, this work expands the methodology to the shoulder and hip joints and further addresses the impact of various exercises on the knee joint in different subject populations. For instance, I outline how patellofemoral cartilage deforms after a series of single-legged hops in anterior cruciate ligament-deficient and intact knees, how body mass index impacts patellofemoral cartilage strain and T1rho relaxation times in the context of walking, how tibial cartilage T1rho relaxation times change over the course of the day due to activities of daily living, and how pushups affect glenohumeral cartilage. I also discuss the development and validation of a semi-automated technique to isolate bones from MRIs, which reduces the time required for manual segmentation by approximately 75% and thus significantly improves research efficiency. As an expansion of the semi-automatic segmentation work, I will cover how I developed a technique to assess the minimum moment of inertia along the femoral neck from clinical computed tomography (CT) scans, with the goal of understanding relative fracture risks between individuals with and without diabetes. Finally, I quantify running-induced changes in knee cartilage thickness and composition (as measured by T1rho relaxation times), as well as changes in hip joint bone-to-bone distances and hip cartilage T1rho relaxation times. Running is a known activity linked to patellofemoral pain, yet the underlying etiology of this condition is unknown. As both knee and hip kinematics have been linked to patellofemoral pain, the goal was to assess how running influences these joints biomechanically and biochemically to better understand why people suffer from patellofemoral pain.