Evolution of DWI Changes in Stroke

DWI provides a technique for the mapping of proton contrast derived from the microvascular water environment (Le Bihan, 2003). In that way, the procedure is sensitive to the translation of water molecules over short distances (diffusion), and can detect ischemia-induced changes in water protons within minutes after an insult (Moseley et al., 1990a,b). During typical periods of observation (A = 40 ms), these distances are on the order of 5 to 20 mm. DWI utilizes a pair of magnetic field gradient pulses placed symmetrically around the 180° refocusing radiofrequency (RF) pulse to dephase and rephase stationary water protons (Stejskal and Tanner, 1965). Diffusive dephasing processes as occurs in the normal extracellular space results in a signal loss, whereas hindrances or slowing of extracellular diffusion leads to signal hyperintensity. Alteration in the time and amplitude of the gradient pulses (the b-value) alters the sensitivity of the image to diffusion with measurements at differing b-values. Incorporation of the matched pulsed gradient pair into an echo-planar imaging (EPI) sequence to measure the apparent diffusion coefficient (ADC) and to produce the ADC map is illustrated in Figure 3.50. A typical example is shown in Figure 3.51.

Images with rising b-values are the basis on which maps of the ADC are calculated (Le Bihan et al., 1992). The physiological background of the ADC was studied in many experimental investigations to show that it closely mirrors the metabolic state of the tissue, and is an indicator of cytotoxic cell edema. The ADC does not decrease until cerebral blood flow falls below a perfusion threshold of 15-20 mL per 100 g min-1 (Roberts et al., 1993; Hossmann, 1994). Hoehn-Berlage and colleagues combined DWI and multiparametrical mapping of ATP, pH, lactate and glucose to show that 2 h after focal ischemia an ADC decrease to 90% of baseline correlated with the area of tissue acidosis, whereas the area of ATP depletion corresponded with an ADC decrease to 70% (Hoehn-Berlage et al., 1995).

The evolution of cerebral ischemia to tissue infarction is characterized by a typical sequence of MRI signal changes. This scenario of ADC changes may be characterized as follows:

1. At very early time points following ischemia (minutes to hours), with regional perfusion lying below a threshold, ADC values are decreased in regions where T2 values are still normal. A low ADC is considered to be an indicator of tissue in metabolic jeopardy, as successful reperfusion can re-establish the ADC to normal values, as seen in numerous animal studies. At these early time points, a low ADC would suggest membrane depolarization with water shift from the extra- to intracellular space (cytotoxic edema) (Moseley et al., 1990c; Rother et al., 1996). Without reperfusion, regions with low ADC will most likely go on to exhibit elevated T2 values, and progress to necrosis unless the underlying perfusion deficit is corrected either on its own or with therapy.

Dwi Epi Sequence

Fig. 3.50. The Stejskal-Tanner (ST) diffusion-weighted spin-echo echo-planar (EPI) MR pulse sequence timing diagram. The ST technique modifies any single- or multi-shot spin-echo sequence with a pair of diffusion-sensitizing gradient "pulses" of strength G (mT-m-1), duration d and separation A. By changing the gradient pulse parameters, the amount of diffusion sensitivity can be controlled and the apparent diffusion coefficient (ADC) measured. This amount is often referred to as the b-value, where b = g2d2G2(A -d/3). To use this method in clinical stroke: (a) images with increasing diffusion weighting (over a range of b-values, 0-800 s mm-2) are acquired sequentially; (b) after which the signal change due to diffusion is fitted to a single exponential of signal intensities against the b-value, the slope of the change being the ADC. (c) The resulting computed ADC map is composed of the slopes for all pixels in the original images. Note that differences in fast and slow diffusion rates (for example between CSF and gray matter) are best visualized at higher b-values, given sufficient SNR. The DWI "exam" must contain both a low and a series of higher b-values of at least 400-500 s mm-2 to visualize diffusion effects in stroke. As the b-value is increased, the ischemic lesion is made more conspicuous by virtue of the lower ADC of ischemic brain compared to faster proton apparent diffusion in normally perfused brain.

2. In the later stages (days), low ADC values are still seen in regions exhibiting elevated T2 (Knight et al., 1994). This can occur when cytotoxic cellular swelling (within intact cells) exists in regions of increased water content. Comparison of T2- and diffusion-weighted images shows a distinct difference in the regional hyperintensities. While elevated T2 may be seen over a large diffuse region (reflecting distributions of extracellular vasogenic water), diffusion-weighted hyper-intensity is confined to sharply defined areas of cytotoxically edematous tissue, since diffusional (ADC) slowing occurs on a cell-by-cell basis. This seemingly paradoxical occurrence in which both vasogenic and cytotoxic water exists, causes both T2- and diffusion-weighted images to be hyperintense. Nonetheless, the diffusion-weighted image is a weighted average of how fast the bulk water signal diffuses; if the majority of the water is hindered or slowed, then the diffusion-weighted images will be hyperintense and the ADC will be lower than normal.

4 hours T2-wt.

4 hours DWI

4 hours ADC

Dwi Brain Ischemia

Fig. 3.51. A series of diffusion-weighted images of human brain at 4 h after onset of cerebral ischemia. EPI T2-weighted (in which no diffusion-weighting is applied, b = 0), the corresponding diffusion-weighted images (b = 881 s mm"2), and the calculated ADC maps for four slices of 16 images acquired from a patient at 4 h after onset of hemi spheric aphasia. This is then compared to the T2-weighted images acquired at 5 days. Note that the DWI depiction of lesion volume does not significantly decrease over the first 5 days, and is similar in volume to the corresponding relative cerebral blood volume maps (not shown).

Fig. 3.51. A series of diffusion-weighted images of human brain at 4 h after onset of cerebral ischemia. EPI T2-weighted (in which no diffusion-weighting is applied, b = 0), the corresponding diffusion-weighted images (b = 881 s mm"2), and the calculated ADC maps for four slices of 16 images acquired from a patient at 4 h after onset of hemi spheric aphasia. This is then compared to the T2-weighted images acquired at 5 days. Note that the DWI depiction of lesion volume does not significantly decrease over the first 5 days, and is similar in volume to the corresponding relative cerebral blood volume maps (not shown).

3. In regions of complete infarction, both T2 and ADC are observed to be higher than normal within similar regional distributions. The corresponding histo-pathology of these regions indicates cellular necrosis, in which cell lysis breaks down water diffusion barriers leading to an increase in ADC.

This situation can last for up to 10 days, until the ADC values return to ''pseudonormal''. However, as the diffusion-weighted images are also T2-weighted, regional hyperintensity may be seen on DWI, even though the ADC is now above normal. This regional hyperintensity is of course due to the elevated T2, and is not a sign of acute ischemia but rather of cerebral infarction. Because of this ''T2 shine through'', every DWI examination must also include the ADC map, for these very reasons.

From the behavior of ADC and T2 described above, the potential exists to determine the age of lesions, a clinical tool of enormous relevance in daily routine.

382 | 3.3 Modern Applications of MRI in Medical Sciences 3.3.3.3

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