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Arterial spin labeling perfusion predicts longitudinal decline in semantic variant primary progressive aphasia

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Abstract

The objective of the study was to evaluate the prognostic value of regional cerebral blood flow (CBF) measured by arterial spin labeled (ASL) perfusion MRI in patients with semantic variant primary progressive aphasia (svPPA). We acquired pseudo-continuous ASL (pCASL) MRI and whole-brain T1-weighted structural MRI in svPPA patients (N = 13) with cerebrospinal fluid biomarkers consistent with frontotemporal lobar degeneration pathology. Follow-up T1-weighted MRI was available in a subset of patients (N = 8). We performed whole-brain comparisons of partial volume-corrected CBF and cortical thickness between svPPA and controls, and compared baseline and follow-up cortical thickness in regions of significant hypoperfusion and hyperperfusion. Patients with svPPA showed partial volume-corrected hypoperfusion relative to controls in left temporal lobe and insula. svPPA patients also had typical cortical thinning in anterior temporal, insula, and inferior frontal regions at baseline. Volume-corrected hypoperfusion was seen in areas of significant cortical thinning such as the left temporal lobe and insula. Additional regions of hypoperfusion corresponded to areas without cortical thinning. We also observed regions of hyperperfusion, some associated with cortical thinning and others without cortical thinning, including right superior temporal, inferior parietal, and orbitofrontal cortices. Regions of hypoperfusion and hyperperfusion near cortical thinning at baseline had significant longitudinal thinning between baseline and follow-up scans, but perfusion changes in distant areas did not show progressive thinning. Our findings suggest ASL MRI may be sensitive to functional changes not readily apparent in structural MRI, and specific changes in perfusion may be prognostic markers of disease progression in a manner consistent with cell-to-cell spreading pathology.

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Acknowledgments

This work was supported in part by the National Institutes of Health: AG017586, AG043503, AG015116, NS044266, AG032953, the Wyncote Foundation, and the Arking Family Foundation. Open-source ANTs software, available at https://github.com/stnava/ANTs, was used to process T1 and pCASL images. No funding source played a role in the study design, in the collection, analysis and interpretation of the data, in the writing of the report, or in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Neurology, Penn Frontotemporal Degeneration Center, University of Pennsylvania Perelman School of Medicine, 3 West Gates, Philadelphia, PA, 19104, USA

    Christopher A. Olm, Murray Grossman & Corey T. McMillan

  2. Department of Radiology, Penn Image Computing and Science Lab, Philadelphia, PA, 19104, USA

    Benjamin M. Kandel, Brian B. Avants & James C. Gee

  3. Departments of Neurology and Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    John A. Detre

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  1. Christopher A. Olm
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Correspondence to Corey T. McMillan.

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Prior to inclusion in the study, all participants participated in a written informed consent procedure under a protocol approved by the Institutional Review Board at the University of Pennsylvania in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Olm, C.A., Kandel, B.M., Avants, B.B. et al. Arterial spin labeling perfusion predicts longitudinal decline in semantic variant primary progressive aphasia. J Neurol 263, 1927–1938 (2016). https://doi.org/10.1007/s00415-016-8221-1

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