Diffusion weighted & tensor spectroscopy

Diffusion weighted spectroscopy (DWS) and diffusion tensor spectroscopy (DTS)

Francesca Branzoli, Hermien Kan, Andrew Webb (LUMC), Daniel Reich, Emily Wood (NIH/NINDS, Bethesda MD, USA), Aranee Techawiboonwong (Mahidol University, Bangkok, Thailand), Itamar Ronen

Background

Diffusion based MRI methods such as diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) provide a link between imaging and the microscopic structural properties of tissue. The relative sensitivity of such methods is offset by their lack of specificity, as the signal source for these methods (i.e. water) resides in all tissue compartments. Specificity can be gained by a variety of methods, and one of them is to focus on biological markers that reside in specific tissue compartments – neurons and axons, glia and other compartments of interest. Diffusion weighted spectroscopy (ref) provides compartment specific structural information that together with information obtained from other MR modalities can better explain microstructural and physiological processes in the brain.

Goals

Develop robust methodology for single volume and 2D DWS and DTS for 7T and 3T MR scanners;

  • Characterize white matter microstructure;
  • Elucidate compartmental tissue damage in neurological disorders;
  • investigate physiological changes upon neuronal activation

Approach

The following two sections describe our approach to the last two goals specified above, namely, the investigation of physiological changes upon neuronal activation in the visual cortex, and the elucidation of compartmental damage in white matter in multiple sclerosis (MS).

  1. Functional DWS of the human visual cortex at 7T
    Conventional fMRI provides an indirect measurements of neuronal activity based on the blood oxygenation level-dependent (BOLD) contrast. Recently, methods have been proposed that are not based on the hemodynamic response coupled to neuronal activation, but rather on changes related to metabolism or cellular properties, which are more tightly correlated to the neuronal event. We use diffusion weighted spectroscopy (DWS) to bring to light changes in the properties of mobility of intracellular metabolites such as N-acetyl aspartate (NAA), creatine/phosphocreatine (tCr) and choline compounds (tCho) in response to activation. So far we have detected robust changes in the apparent diffusion coefficient (ADC) of tCr in response to visual stimulation. These changes may reflect activation-induced changes in the creatine kinase cycle. Shown below are the functional paradigm, the activated region (yellow) as detected with an fMRI experiment with the location of the volume of interest for the DWS experiment (red rectangle), a typical spectrum from the region and the averaged time course of the ADC of the tCr peak.
  2. Figure 1

  3. Microstructural properties of white matter tracts in health and disease as seen with DWS at 7T
    In previous works we have shown that DWS and DTS are exquisitely sensitive to variations in axonal organization and microstructural properties of white matter tracts. We have now applied DWS to characterize the diffusion properties of NAA, tCr and tCho in the human corpus callosum. In collaboration with Dr. Daniel Reich and Emily Wood from the National Institute of Neurological Disease and Stroke at the National Institutes of Health (NINDS/NIH, Bethesda MD) we performed the first clinical application of DTS – the possible detection early axonal damage in multiple sclerosis (MS). The target of this DTS measurement was the neuronal/axonal marker N-acetyl aspartate (NAA). When diffusion properties of NAA in the corpus callosum was measured in a group of MS subjects and compared to those measured in healthy controls (HC), the diffusion coefficient of NAA parallel to the axonal fibers was significantly lower in MS subjects than in healthy controls, raising the possibility of axonal disruption. The parallel diffusivity correlated well also with clinical outcome of the MS subjects as measured with the Extended Disability Status Scale (EDSS) testFigure 2

Selected publications

  1. Kan, H. E., A. Techawiboonwong, M. J. van Osch, M. J. Versluis, D. K. Deelchand, P. G. Henry, M. Marjanska, M. A. van Buchem, A. G. Webb and I. Ronen (2011). "Differences in apparent diffusion coefficients of brain metabolites between grey and white matter in the human brain measured at 7 T." Magn Reson Med.
  2. Upadhyay, J., K. Hallock, M. Ducros, D. S. Kim and I. Ronen (2008). "Diffusion tensor spectroscopy and imaging of the arcuate fasciculus." Neuroimage 39(1): 1-9.
  3. Upadhyay, J., K. Hallock, K. Erb, D. S. Kim and I. Ronen (2007). "Diffusion properties of NAA in human corpus callosum as studied with diffusion tensor spectroscopy." Magn Reson Med 58(5): 1045-1053.

Status

The project started in 2006 (active)

Contact

Itamar Ronen, i.ronen@lumc.nl

+31-71-5265479