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Prediction of Infarct Core and Salvageable Ischemic Tissue Volumes by Analyzing Apparent Diffusion Coefficient Without Intravenous Contrast Material

Posted Nov 30, 2010 Updated Apr 7, 2023
By Li Ma MD , Pei-Yi Gao MD , Qing-Mao Hu PhD , Yan Lin MMedSc , Li-Na Jing MD , Jing Xue MD , Xiao-Chun Wang MD , Zhi-Jun Chen MSc , Yi-Long Wang MD , Xiao-Ling Liao MD , Mei-Li Liu MD , Wei-Jian Chen MD
14 min read

Rationale and Objectives

To investigate whether baseline apparent diffusion coefficient (ADC) maps can be employed to predict both infarct core and salvageable ischemic tissue volumes in acute ischemic stroke.

Materials and Methods

An automated image analysis system based on baseline ADC maps was tested against 30 patients with acute ischemic stroke of anterior circulation to predict both infarct core and salvageable ischemic tissue volumes. The predicted infarct core and predicted salvageable ischemic tissue were quantitatively and qualitatively compared with follow-up imaging data in recanalization and no recanalization groups, respectively. Direct comparisons with perfusion- and diffusion- weighted magnetic resonance imaging measures were also made. Wilcoxon signed-rank test, Spearman rank correlation, and Bland-Altman plots were performed.

Results

In the recanalization group, the predicted infarct core volume was significantly correlated with the final infarct volume ( r = 0. 868, P < .001). In the no recanalization group, the predicted final infarct volume (sum of the predicted infarct core and salvageable ischemic tissue volumes), as well as the predicted salvageable ischemic tissue volume, was also significantly correlated with the true final infarct volume ( r = 0.955, P < .001) and infarct growth ( r = 0.918, P < .001), respectively. The volumes of perfusion-diffusion mismatch were significantly larger than those of infarct growth and predicted salvageable ischemic tissue. Good agreement between predicted and true final infarct lesions was visualized by Bland-Altman plots in two groups. Direct visual comparative analysis revealed good qualitative agreement between the true final infarct and predicted lesions in 21 patients.

Conclusion

The proposed ADC based approach may be a feasible and practical tool to predict the volumes of infarct core and salvageable ischemic tissue without intravenous contrast media–enhanced perfusion-weighted imaging at baseline.

The ischemic penumbra is defined as tissue at risk of infarction but with the potential to recover . Current clinical imaging protocol for acute ischemic stroke attempts to identify irreversible injured brain tissue and the ischemic penumbra. Accurate and rapid estimation of the size of these regions during the early therapeutic window will influence the very choice of the most effective therapy and be necessary to estimate the likely benefit after treatment . Currently, multimodal magnetic resonance imaging (MRI) modalities, including diffusion-weighted imaging (DWI), dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI), and magnetic resonance angiography (MRA) are recommended by the guidelines as the most clinically useful tools to characterize the ischemic deficit in a clinical setting . The mismatch between a larger lesion on DSC-PWI and a smaller lesion on DWI has been widely used to mirror the ischemic penumbra, and the concept of the penumbra has been represented by that of PWI-DWI mismatch .

However, the PWI-DWI mismatch model suffers from several serious drawbacks and has been greatly challenged . First, DWI abnormal areas, which are widely used as routine protocols to delineate irreversibly infarct tissues in the PWI-DWI mismatch model, may still be viable and reversible . In addition, DWI signal intensity depends on variable factors such as confounding T2 effects and diffusion rate of water molecules. Second, it has not been determined yet which DSC-PWI parameter most closely identifies tissue at risk . The PWI abnormal areas cannot reliably distinguish the penumbral tissue from oligemia. Consequently, the putative ischemic penumbra is in rather crude estimates and may be overestimated, which may result in overtreatment of thrombolysis . Furthermore, DSC-PWI requires intravenous contrast agent injection, is invasive and tedious in limited time scheme of acute ischemic stroke, and is contraindicated in cases of severe renal insufficiency. Although arterial spin labeling can be used to measure perfusion deficits noninvasively, it is usually used for imaging cerebral blood flow. Cerebral blood flow is more difficult to be visually interpreted as prolonged mean transit time (MTT) obtained by DSC-PWI , as recommended by the guidelines for acute stroke imaging . Cerebral blood flow also has lower intrinsic signal to noise than MTT for accurate volume measurement . Finally, volume measurements of the DWI and PWI lesions for quantifying the mismatch are currently performed through manual outlining, which is tedious and unreliable among observers, and may in turn lead to inaccurate clinical characterization of the individual patient and underpowered clinical trials . Thus, overcoming these drawbacks may require standardized and automatic approaches to obviate the need for manually delineating the volumes.

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Materials and methods

Patients

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Imaging

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Quantitative Analysis

Predicted volumes through ADC-based method

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Figure 1, Stroke magnetic resonance imaging (MRI) was performed 4.4 hours after symptom onset in this 73-year-old male. Baseline MRI showed an acute ischemic lesion in the left basal ganglion with diffusion-weighted imaging perfusion-weighted imaging mismatch in the left middle cerebral artery (MCA) territory (a, b, d, e) . The patient had recanalization of the left MCA (f) and early reperfusion (g) after thrombolysis. The global shape of predicted infarct region (c , marked in red ) was correspondent to final infarct region (h) .

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Lesion volume through manually drawing regions of interest

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Qualitative Analysis

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Statistical Analyses

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Results

Patients

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Table 1

Patient Data of Recanalization Group

Baseline Volumes (mL) Follow-up Volumes (mL) Patient No. Age (y) Sex Treatment Vol IR Vol DWI Vol final 1 45 M IA 2.26 4.18 4.60 2 71 M IV 0.82 1.90 5.68 3 68 M — 12.35 12.35 15.54 4 45 F IA 27.59 23.26 65.26 5 68 M IA 19.39 39.25 34.97 6 47 M IA 5.68 10.06 8.16 7 70 F — 13.41 11.46 16.84 8 73 F IA 1.83 1.70 2.00 9 48 M IA 16.83 26.17 20.04 10 44 F — 10.60 9.96 10.66 11 57 M IV 0.63 1.82 3.68 12 73 M IV 3.66 3.74 3.93 13 70 F — 13.23 17.25 19.30 14 41 F IV 1.64 4.08 3.04 15 40 M IV 5.84 6.30 7.10 16 62 F IV 3.37 6.24 25.00 17 61 F IV 1.92 4.32 4.74 18 74 M IV 0.47 4.39 0.84 19 70 F IV 4.31 4.67 6.25

Vol IR , predicted infarct core volume; Vol DWI , baseline diffusion-weighted imaging lesion volume; Vol Final , final infarct volume.

Table 2

Patient Data of No Recanalization Group

Baseline Volumes

(mL) Follow-up Volumes (mL) Patient No. Age (y) Sex Treatment Vol IR Vol TR Vol IR+TR Vol DWI Vol PWI Vol PWI-DWI Vol final Vol IG 20 51 M IV 8.00 5.63 13.63 7.22 152.42 145.19 11.40 4.18 21 51 M — 1.73 7.31 9.04 2.80 12.40 9.61 2.27 −0.52 ∗ 22 55 M IA 7.59 8.71 16.30 8.84 155.21 146.36 16.48 7.63 23 53 M — 10.76 13.54 24.30 10.02 123.92 113.91 24.08 14.06 24 52 M IV 56.58 47.33 103.91 56.56 117.84 61.29 93.82 37.26 25 45 M — 26.32 52.73 79.05 29.87 288.40 258.54 87.06 57.19 26 51 M — 3.78 3.71 7.49 5.26 54.44 49.18 3.12 −2.13 ∗ 27 65 F — 7.56 6.36 13.92 10.94 224.22 213.28 15.08 4.14 28 59 M — 12.89 23.63 36.52 24.02 270.32 246.30 42.66 18.64 29 60 M IV 6.70 8.66 15.36 8.48 168.14 159.66 14.10 5.62 30 43 M IV 1.59 2.37 3.96 2.03 70.39 68.36 5.15 3.12

Vol IR , predicted infarct core volume; Vol TR , predicted salvageable ischemic tissue volume; Vol IR+TR , the sum of predicted infarct core and predicted salvageable ischemic tissue volumes; Vol DWI , baseline diffusion-weighted imaging lesion volume; Vol PWI , baseline perfusion-weighted imaging lesion volume; Vol PWI-DWI , difference between baseline PWI lesion and baseline DWI lesion; Vol Final , final infarct volume; Vol IG , infarct growth volume.

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Quantitative Analysis

Predicted infarct core volume versus final infarct volume

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Figure 2, (a) Scatter plots depict predictions of Vol Final based on Vol IR and Vol DWI in recanalization group. Vol Final was plotted along the y axis, baseline Vol IR and Vol DWI were plotted along the x axis. The solid spots represent Vol IR , and the circles represent Vol DWI . Both lines are not constrained by a forced zero intercept. (b) Scatterplots of Vol IR+TR versus Vol Final and Vol PWI versus Vol Final in no recanalization group. Vol Final was plotted along the y axis, baseline Vol IR+TR and Vol PWI were plotted along the x axis. The solid spots represent Vol IR+TR , and the circles represent Vol PWI . (c) Scatterplots of Vol TR versus Vol IG and Vol PWI-DWI versus Vol IG in no recanalization group. Vol IG was plotted along the y axis, baseline Vol TR and Vol PWI-DWI were plotted along the x axis. The solid spots represent Vol TR , and the circles represent Vol PWI-DWI . All the lines are not constrained by a forced zero intercept. Vol Final , final infarct volume; Vol IR , predicted infarct core volume; Vol DWI , baseline diffusion-weighted imaging lesion volume; Vol TR , predicted salvageable ischemic tissue volume; Vol PWI , baseline perfusion-weighted imaging lesion volume; Vol IG , infarct growth volume; Vol PWI-DWI , difference between baseline PWI lesion and baseline DWI lesion.

Figure 3, Bland-Altman plots of the variability in volume measurement: (a) Vol IR versus Vol Final and (b) Vol DWI versus Vol Final in recanalization groups; (c) Vol IR+TR versus Vol Final , (d) Vol TR versus Vol IG and (e) Vol PWI versus Vol Final in no recanalization groups. The mean of two sets of measurements is plotted on the horizontal axis, against their difference on the vertical axis. The solid line represents the mean of the difference, and the dashed lines represent the upper and lower boundaries of 95% confidence intervals. See Figure 2 for abbreviations.

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Baseline DWI volume versus final infarct volume

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Predicted salvageable ischemic tissue volume versus infarct growth volume

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PWI-DWI mismatch volume versus infarct growth volume

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Qualitative Visual Analysis

Predicted infarct core versus final infarct lesion in recanalization group

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Predicted infarct core and salvageable ischemic tissue versus final infarct lesion in no recanalization group

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Figure 4, The 43-year-old patient underwent stroke magnetic resonance imaging 1.73 hours after symptom onset. Initial DWI and ADC maps demonstrated an acute ischemic lesion adjacent to body of lateral ventricle (a, b) . With left MCA occlusion (d) , there was a larger area of prolonged MTT (e) which exceeded the initial DWI lesion (a) (ie, PWI-DWI mismatch). After thrombolysis, follow-up magnetic resonance angiogram showed that no recanalization occurred (f) . The final infarct region (f) was not as large as initial PWI lesion area (e) but as the predicted final infarct volume (sum of predicted infarct core and predicted salvageable ischemic tissue volumes) ( c , marked in red and green , respectively) obtained by the approach. See Figure 2 for abbreviations.

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Discussion

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Infarct Core: ADC-based Approach versus Baseline DWI

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Ischemic Salvageable Ischemic Tissue: ADC-based Approach versus PWI/DWI Data

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Qualitative Agreement: ADC-based Approach versus Follow-up Data

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Comparison with Previous Studies

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Table 3

Comparison with Previous Studies using ADC to Predict Salvageable Ischemic Tissue

Paper Determination of Infarct Core Volume at Baseline Semi- or Fully Automated Processing Time (min.) Group or Individual Level Comparison with PWI-DWI Mismatch Data Statistical Analysis of Volumes Results Present study Automated segmentation of the baseline ADC Fully automated 1 Individual level Provided Wilcoxon

Spearman

Bland-Altman plots_r_ = 0.868 for predicted infarct core volume;

r = 0.918 for predicted salvageable ischemic tissue Montiel Manual segmentation of the baseline DWI Semi automated <10 Group level Not provided Spearman_r_ = 0.65 for predicted infarct growth Rosso Manual segmentation of the baseline DWI Semi automated 10 Group level Not provided Spearman_r_ = 0.828 or 0.777 for predicted final infarct volume;

r = 0.506 or 0.479 for predicted infarct growth

ADC, apparent diffusion coefficient; DWI, diffusion-weighted imaging; PWI, perfusion-weighted imaging.

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Limitations of the Study

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Conclusions

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Acknowledgments

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Academic Radiology, Volume 17, Issue 12
Journals General Radiology
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