The MIPP study: Monitoring Intracranial atherosclerotic Plaque Progression using high resolution MRI - initial results
Chengcheng Zhu1, Xuefeng Zhang2, Andrew J Degnan3, Qi Liu2, Luguang Chen2, Zhongzhao Teng4, David Saloner1, and Jianping Lu2

1Radiology, University of California, San Francisco, San Francisco, CA, United States, 2Radiology, Changhai Hospital, Shanghai, China, People's Republic of, 3Radilogy, University of Pittsburgh, Pittsburgh, PA, United States, 4Radiology, University of Cambridge, Cambridge, United Kingdom

Synopsis

Intracranial large artery atheroma is a major cause of stroke, however its natural history is still poorly understood. In this study we followed 63 symptomatic patients who had intracranial atherosclerotic plaque for up to 3 years. Multi-contrast black blood vessel wall MRI and clinical brain imaging were performed. Initial results included 22 patients who were followed for 6 months showed an overall plaque volume progression rate of 0.8%, however with a large standard deviation (20.1%) and range (-45.9% to 40.1%). Patients with hypertension or low HDL tended to progress faster. The feasibility of MRI for monitoring intracranial plaque pathological changes was demonstrated.

Purpose

Intracranial large artery atheroma is a major cause of stroke worldwide, however the optimal treatment has not been established 1. With the development of high resolution black blood MRI techniques, intracranial vessel wall characteristics have been increasingly studied as possible markers of neurological symptoms 2. However, the natural history of intracranial atherosclerotic plaque is still poorly understood. Previous longitudinal studies using angiography or trans-cranial ultrasound failed to evaluate pathological changes of the vessel wall 3. This study aims: 1) to evaluate the feasibility of MRI for monitoring intracranial plaque progression in patients with recent stroke or TIA, and 2) to preliminary investigate the possible risk factors correlated with plaque progression and recurrence of ischemic events.

Methods

Study population: 63 patients (49 male, mean age 66) with recent stroke or TIA who were identified with intracranial artery stenosis were recruited in the MIPP study. 76 stenotic intracranial arteries were identified including 65 middle cerebral arteries (MCAs) and 11 basilar arteries (BAs). Patients first underwent baseline MRI imaging, and then were followed with repeated MRI at least once (follow up time 3 months to 3 years). Recurrence of neurological symptoms during the follow up period was recorded. All patients were under best medical therapy. MRI acquisition: For each visit, patients underwent multi-contrast high resolution MRI of the plaque and clinical brain MRI. Plaque imaging included black blood sequences: pre- and post-Gd contrast T1-weighted fast spin echo (FSE), T2 and proton-density (PD) weighted FSE. An in-plane resolution of 0.4mm and a slice thickness of 2mm were used. Brain imaging included T1/T2-weighted FSE, FLAIR and DWI. Image analysis: Lumen and outer wall boundaries were manually segmented on T2-weighted images by a radiologist and the plaque area and volume were quantified. Contrast enhancement on T1-weighted MRI was graded by three categories: 0: no enhancement; 1: possible enhancement; 2: obvious enhancement. Statistics: T-tests were used to compare the group differences. We documented patient clinical characteristics and performed multivariable logistic regression analysis to investigate their correlation with plaque progression.

Results

In this initial report, we analysed data from 22 patients (18 male, age 56±13, stenosis 70.2±22.9%) with follow up scan at ~6 months. 26 plaques were identified (22 MCAs, 4 BAs). Two patients had recurrent TIAs; however, no additional infarcts were identified on DWI in all patients. Overall there was no significant plaque volume change (annual progression rate: 0.8±21.0%), however with a big SD and range (-45.9% to 40.1%). Representative images of patients with plaque progression (Figure 1), regression (Figure 2) and no change (Figure 3) are shown. At baseline, 4 plaques showed no enhancement, 8 plaque showed possible enhancement, and 10 plaques showed strong enhancement. At follow up, 5 plaques showed a category decrease in contrast enhancement, while 17 plaques were un-changed. Regression analysis showed that there was no significant correlation between clinical factors, contrast enchantment status, stenosis values or baseline volume with progression rate (p>0.05). However, patients with hypertension tended to progress faster compared with patients without hypertension with a borderline significance (p=0.057) (Table 1), and there was a moderate inverse relationship between baseline HDL levels and plaque progression (Pearson’s r = -0.34, p=0.08, Figure 4).

Discussion

To our best knowledge, this is the first study that reports the natural history of the intracranial artery wall. We showed that high resolution MRI is feasible for monitoring intracranial plaque progression even during a relatively short period of time. Plaque volume and contrast enhancement changes were evident, indicating an active progress of the intracranial plaque development. Therefore, vessel wall MRI has the potential to evaluate treatment response in a short period of time, rather than waiting for patient long-term outcome data. The current initial report is limited by a small sample size and short follow up time, thus the statistics did not reach significance. Plaque volume was used in this study as the only end point given that only two patients had recurrent TIAs. In a previous reproducibility study 4, we have proved that plaque volume was more sensitive to detect changes compared with plaque area.

Conclusion

High resolution vessel wall MRI is feasible to monitor intracranial plaque progression and pathological changes in a short period of time. These techniques can be potentially used to better understand the natural history of intracranial plaque, evaluate treatment response, and investigate risk factors associated with future ischemic events.

Acknowledgements

This study is supported by NIH grants R01HL114118 and R01NS059944.

References

1. Arenillas, J. F. Intracranial atherosclerosis: current concepts. Stroke; a journal of cerebral circulation 42, S20-23, (2011).

2. Dieleman, N. et al. Imaging intracranial vessel wall pathology with magnetic resonance imaging: current prospects and future directions. Circulation 130, 192-201, (2014).

3. Komotar, R. J. et al. Natural history of intracranial atherosclerosis: a critical review. Neurosurgery 58, 595-601; discussion 595-601, (2006).

4. Zhang, X. et al. Scan-Rescan Reproducibility of High Resolution Magnetic Resonance Imaging of Atherosclerotic Plaque in the Middle Cerebral Artery. PloS one 10, e0134913, (2015).

Figures

Figure 1. A patient with MCA plaque shows progression on T2 weighted images.

Figure 2. A patient with basilar plaque shows regression of the plaque at follow up. Plaque area was reduced as shown on T2-weighted images, and plaque enhancement was also reduced on post-contrast T1 weighted images.

Figure 3. A patient with MCA plaque shows stable status on T2 weighted images.

Table 1. Patient demographical data and annual progression rate by groups.

Figure 4. Relationship between HDL-C levels and plaque progression.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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