Techniques for Rotating Frame Magnetic Resonance
This subproject exploits the endogenous contrast mediated via water molecules in the presence of slow motions of macromolecules associated with different biological tissues. Early detection of molecular changes that precede gross morphological changes in pathologies is critical for stopping the disease progression and/or reversing the course of the disease. Specifically, it focuses on the T1ρ relaxation time constant and its role in early detection of molecular changes in pathologies such as arthritis, intervertebral disc degenerative disease (DDD), Alzheimer’s disease (AD) and cancer. The current project expands upon the developments and progress made in the previous funding period. While excellent progress has been made with this method and its applications, there are several limitations in exploiting the method to its fullest potential and hence there are challenging needs, which remain unmet.
Briefly, in the current implementation, the method is inherently inefficient because the T1ρ contrast is lost during the repeated excitation and relaxation, which occurs during multi-echo acquisitions. It also suffers from inefficient lipid suppression due to the inherent nature of the readout pulse sequence. Further, given the RF power deposition issues, we were unable to achieve or use B1 fields > 500 Hz in vivo. This corresponds to restricted motional range with time scales of ~ 2ms. This also limits the efficiency of T1ρ in cases where the internal interactions correspond to > 500Hz. Therefore, to probe the motions in μs to ms range it is important that we achieve an effective field >1kz, while maintaining high spatial resolution and keeping the RF power deposition under approved SAR guidelines even at ultra high fields.
To achieve these requirements, the current project proposes to develop a new method. Once developed and validated, this method, in addition to improving RF power and time efficiency of T1ρ MRI, it also opens up avenues for probing molecular motions over a large frequency range. It potentially enables studies at ultra high fields with built in lipid suppression and obtaining dispersion weighted contrast in different types of tissues. It may also play a role as optimal readout sequence for other applications such as fMRI and arterial spin labeling in ultra high fields.
Techniques for Dynamic Contrast-Enhanced MRI
The second subproject exploits high temporal and spatial resolution imaging strategies to study dynamics of exogenous contrast agent in different pathologies. With the advent of targeted biologic therapies in cancer treatment, a new challenge of imaging as a means of assessing therapeutic efficacy has arisen. Traditional means of assessing treatment response in solid tumors, the RECIST criteria, which are strictly based on lesion size, may not provide the most relevant endpoint. With its ability to image blood flow and vessel permeability, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays a critical role in diagnosis of tumors and in the assessment of its response to these targeted therapies. However, many challenges remain in the DCE-MRI techniques currently used in practice.
High temporal resolution is typically required to accurately determine tumor enhancement kinetics, while sufficient spatial resolution is needed for the detection of small lesions and assessment of lesion heterogeneity. However, there is a tradeoff between high temporal and high spatial resolutions, and it is difficult to acquire both sets of data in a single scan due to their disparate demands. The potential need for large volume or whole-organ imaging for the analysis of multiple metastatic lesions further increases the need for longer scan times. Additional problems arise in dynamic assessment of lesions in the chest or the abdomen. Respiratory motion hampers accurate assessment of the contrast kinetics, often reducing the number of analyzable data in clinical trials. Multiple breath-held scans have generated only limited success, and the method is vulnerable to inconsistent positions of suspended respiration. With existing technology, it is therefore extremely difficult to accurately assess perfusion of lung or liver tumors.
The primary objective of this subproject is to develop effective strategies for improved quantification of tumor vascular characteristics in 3D DCE-MR1. Building upon our ongoing work, we will develop refined methods to address the problem of physiologic motion with novel respiratory motion compensation strategies; investigate methods to enhance the temporal resolution of the dynamic image series, while maintaining high spatial resolution and large volume coverage; and ultimately improve the measurement accuracy of the tumor contrast kinetics. Better imaging of the tumor microenvironment by DCE-MRI may provide a more accurate assessment of the effect of new biologic agents than conventional techniques, thereby allowing clinicians to better direct patient treatment.