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Contents |
Overview
Lab Members
John Detre / JiongJiong Wang / Ronald Wolf / Geoffrey Aguirre / Mark Elliott / Jennie Chen / Jin-Moo Lee / Arjun Yodh / Brett Cucchiara
About the Core
| This TR&D focuses on the use of MRI to study tissue function, and builds upon almost two decades of work using arterial spin labeling (ASL) to measure tissue perfusion. Blood flow is a critical pathophysiological parameter and disorders of blood flow are responsible for a large proportion of medical morbidity. Noninvasive imaging of blood flow is also a promising biomarker with a broad range of applications in biomedicine. While blood flow is the key parameter in the evaluation of vascular disorders, blood flow is also an increasingly important parameter in evaluating neoplastic disease and particularly the effects of anti-angiogenesis therapies. Finally, in the brain and other organs, changes in blood flow are coupled to changes in regional metabolism, allowing blood flow to be used as a biomarker for normal tissue function. The ASL method was initially conceived by this Regional Resource, and continues to provide opportunities for technology development and translation to clinical applications. ASL perfusion MRI remains one of the few MRI contrast mechanisms for which the physiological and biological significance is well understood. |
| Technical developments in ASL, many of which were pioneered under this RR, have resulted in a ten-fold increase in the sensitivity of ASL over the past decade. Collaborative research performed under this RR has also demonstrated many of the translational applications of ASL that have been published to date. While the recent availability of a clinical ASL “product” will undoubtedly lead to a dramatic expansion of its use in clinical care, there remain further opportunities for developing ASL methods and applications. Because of the complementary benefits of increased signal-to-noise and T1 prolongation with increasing magnetic field strength, ASL is expected to benefit heavily from extension to experimental systems operating at ultra-high fields of 7 Tesla or higher, where another 3-4-fold increase in sensitivity is theoretically possible. Development of 7T ASL for use in humans is the first aim of the next project period. This should allow not only better and more reliable images of blood flow, but also provide sufficient sensitivity to more carefully evaluate the biological and biophysical parameters that influence measured signal changes, as proposed in Aim 2. |
| A shortcoming of MRI technologies is that they require costly instrumentation that can only be used sporadically in individual patients, and entails logistical considerations due to the MRI environment and its location in a Department of Radiology. In contrast, optical methods for measuring tissue blood flow and metabolism are much more portable and are compatible with more frequent or even continuous monitoring at the patient’s bedside. Accordingly, another thrust of our overall research in functional imaging is to try to combine these complementary modalities for simultaneous and sequential use. These efforts comprise Aim 3 of our program, and focus primarily on cross-validation of a Diffuse Correlation Spectroscopy, a novel approach for optical measurement of tissue blood flow. |
Active Research
Translational Applications of ASL
| Project 1 concerned ASL methods development and translational applications of ASL, including implementations at 3T and applications in patient populations. We successfully optimized parameters for amplitude-modulated CASL at 3T as well as for the more recently-described pseudo-continuous labeling scheme that provides greater labeling efficiency and compatibility with the RF electronics for body coil transmission. The sensitivity of these approaches has been compared to the more widely used PASL labeling scheme and the expected benefits of CASL and pCASL have been confirmed. We have also carried out more detailed modeling of the effects of relaxation parameters on ASL quantification at high field and on the use of ASL to measure water permeability in the brain. |
| We have explored several approaches to reducing susceptibility artifacts in ASL perfusion MRI data including the use of spin echoes, parallel imaging, and collaborative studies with Dr. David Feinberg on 3DGRASE imaging. We also implemented a background-suppressed 3D-GRASE ASL sequence for use in examining task activation in a regions of high susceptibility gradients and demonstrated its use in “snapshot” imaging in human stroke. We also compared the temporal SNR of pCASL and PASL, demonstrating reduced cardiac noise in pCASL. Finally, we have developed signal processing strategies to reduce noise in ASL data through data cleaning and optimized smoothing and have developed novel strategies for detecting task or population effects in ASL data. |
| In collaborative research, we have applied these ASL sequences to a variety of clinical populations, using TR&D resources to make modifications to data acquisition and analysis procedures as required. Unmodified sequences were used in studies of nicotine abstinence and craving including genotype effects, to study patients with AIDS encephalopathy, to demonstrate correlations between CBF and tumor grade in patients with brain tumors, to demonstrate correlations between CBF and other clinical parameters in patients with pediatric stroke, to examine the influence of resting CBF on task activation in a cohort of patients with chronic stroke, to study a population of teenagers exposed to cocaine in utero, and to measure pharmacological responses to the anesthetic remifentanil. We modified PASL sequences to reduce artifacts in CBF measurements in studies of neonates with congenital heart disease, to measure hemispheric CBF before and after carotid endarterectomy, and we carried out additional theoretical development to validate CASL studies of skeletal muscle. |
| In the area of basic science, we have used PASL to study normal infant brain development and we have used CASL to demonstrate the low-frequency sensitivity of ASL fMRI for cognitive neuroimaging during motor learning natural vision, psychological stress, working memory and attention, and overt narrative speech. A particularly promising avenue of research concerns the use of ASL as a biomarker of brain function at rest, which has been used to demonstrate genotype effects in brain function. We have also collaborated with TR&D 4 investigators on concurrent measurements of tissue blood flow using ASL and optical methods . |
Metabolic Correlates of Functional MRI
| Project 2 concerned the development and application of a concurrent ASL-based fMRI and FDG-PET technique for coupling of CBF and CMRGlc at rest and during task activation and the acute administration of caffeine. An initial paper describing an non-quantitative version of the concurrent technique was published and demonstrated the expected correlation between changes in CBF and metabolism [81]. This semi-quantitative study demonstrated a 24% increase in CMRGlc, a 28% increase in CBF, and a 1% increase in BOLD signal within visual cortex, with concordant loci of activation. Following that initial feasibility study, we have modified our approach to include blood sampling during fMRI to allow quantitative CMRGlu to be determined. A second cohort of healthy volunteers are being studied as baseline and following the administration of caffeine. This study is underway and preliminarily demonstrates that caffeine significantly reduces both CBF and CMRGlu (P<0.001 and p=0.003 for n=5 across multiple regions), with particularly significant effects in caudate and cingluate cortex, both of which mediate attention. |
Last modified February 2, 2009 7:59 pm /
