Physiological imaging techniques such as magnetic resonance spectroscopy (MRS), magnetization transfer and blood volume imaging allow insights into central nervous system function, that are not available from conventional structural imaging modalities. These methods allow neuroscientists to investigate brain metabolism, protein content, pH, and hemodynamics of the brain under different conditions, as well as promising to provide clinicians (neurologists, psychiatrists, radiologists and others) with diagnostic and treatment monitoring tools.

Although some of these techniques are reaching technical maturity, others are still in their infancy, and much work still needs to be done to improve spatial resolution and sensitivity, and reduce scan time. This is particularly true for the study of disorders of childhood, which is the major focus of the FM Kirby Center. For instance, proton spectroscopy of the spine is still and unexplored, despite the enormous importance of the spine in many disabling diseases. Also, proton MRS of the brain at very high fields show terrific promise because of its higher signal-to-noise ratio (SNR) and resolution compared to lower fields, many technical challenges need to be overcome before it can be routinely applied in children.
The first aim of this project therefore focuses on technique development for quantitative proton MR spectroscopic imaging (MRSI) of the brain and cervical spinal cord at 3T and 7T. As MRSI moves to higher resolution, larger matrix sizes and increased spatial coverage result in longer scan times. A major effort in this project is the development of  parallel-encoded (e.g. SENSE) and other MRSI schemes for improved MRSI performance and reduced scan times. Integral to this effort is the ongoing development of software for both data acquisition and processing; this software is developed interactively with our collaborators, and is designed to meet the data processing needs of our service projects, as well as being available for download to the scientific community. Examples in the figures show (1) a high resolution SENSE-MRSI scan of normal brain (5 minute scan time) and in patients with (2) HIV and (3) a high grade brain tumor. Figure 4 shows MRSI of the cervical spine in a patient with multiple sclerosis (MS), while figure 5 shows an example of SENSE-MRSI of the normal human brain at 7T.

Another type of ‘physiological’ imaging involves ‘magnetization transfer’ (MT), where image contrast is generated by saturating molecules which exchange with the water signal being imaged. Conventional magnetization transfer imaging looks at the exchange between broad macromolecule signals off-resonance from the water signal; however, by selective irradiation at specific frequencies, it is possible to investigate exchange processes between water and amide protons, for the most part found in the backbone of proteins and peptides in vivo. The amount of magnetization transfer depends on a number of factors, but by appropriate experiment design, it is possible to investigate protein density, pH and other processes. This project involves technique development to optimize amide proton transfer (APT) imaging and conventional MT on 3T and 7T scanners. The role of MT/APT imaging in various neurological diseases (brain tumors, demyelinating diseases) is under active investigation with our collaborators and service projects.
Finally, MRI is increasingly being used for the measurement of cerebral blood flow and blood volume, and over the last few years we have developed a non-invasive method to measure blood volume, called vascular-space occupancy (VASO) imaging. Recent calculations and data acquisitions have shown that the VASO contrast also contains a perfusion contribution, which with appropriate modeling and protocol design can be used to estimate both blood flow and blood volume – this technique is called VAscular Space Labeling (VASL). In this project, develop VASO and VASL are being developed to allow quantification of blood flow and blood volume in patients. These methods, which have relatively low SNR because of the low blood volume of normal brain, will become especially relevant at higher field where improved SNR is expected.