Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain

Abstract

Oscillating gradients were used to probe the diffusion-time/ frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 s, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known microanatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 m, similar to a typical cellular dimension in gray matter. Magn Reson Med 49:206 -215, 2003. © 2003 Wiley-Liss, Inc. Key words: MRI; diffusion; restriction; ischemia; oscillating gradientWhen the Brownian motion of a molecule is physically impeded or hindered, its effective rate of self-diffusion, or apparent diffusion coefficient (ADC), is reduced, and the diffusion is said to be restricted. In tissues, restriction is thought to be a significant mechanism affecting contrast in diffusion-weighted imaging, in both normal and pathological states. In particular, restriction of water by cell membranes is believed to be the dominant mechanism causing diffusion anisotropy in the nervous system (1), and it has also been postulated to play a central role in the marked decline of water ADC in neural tissue following the onset of ischemia (2-4). However, due to hardware limitations, there has been limited direct investigation in vivo of the effects of restrictions on diffusion measurements with MRI. Such observations can be made by measuring ADC as a function of diffusion time.In an NMR diffusion measurement, if the time allowed for spins to migrate is brief enough, restriction will have little impact on the measurement and the ADC will closely reflect the intrinsic diffusion coefficient. As the diffusion time increases and the molecules interact more often with the physical restrictions, the ADC declines toward an asymptotic value. Several such measurements have been made on excised tissue samples (5-9), typically using spectrometers equipped with strong gradients (50 -500 gauss/cm), which allow ADC measurements at relatively short diffusion times.In vivo measurements, however, have been limited by gradient strengths that are typically one or two orders of magnitude smaller, making the minimal diffusion time relatively long. In RIF-1 tumors, Helmer et al. (10) fou...

Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times

“…The pseudo normalization of MD in ischemic WM in humans for decreased diffusion times shows similar trends with work by Does et al 14 and Wu et al 16 in rodent GM that is ischemic. The results also agree with a PGSE study in rats where the estimated diffusion coefficients between ischemic and healthy tissue were more similar at diffusion times near 5 ms compared with 12 ms (based on Figure 2 in Norris et al 20 ).…”

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Anomalous Diffusion of Brain Metabolites Evidenced by Diffusion-Weighted Magnetic Resonance Spectroscopy in Vivo

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On the Vanishing of the t-term in the Short-Time Expansion of the Diffusion Coefficient for Oscillating Gradients in Diffusion NMR

“…Oscillating gradients and extensions [48][49][50][51] have been used in several research studies [27,28,32,35,38,[52][53][54][55][56][57][58][59][60][61][62][63][64][65], among them applications to human brains in vivo [66]. Comparing oscillating gradients to pulsed gradients, the advantage of the oscillating gradients is that the obtainable b-value is higher allowing the assessment of shorter times.…”