Imaging neurodegeneration in Down syndrome: brain templates for amyloid burden and tissue segmentation

Patrick J Lao; Ben L Handen; Tobey J Betthauser; Karly A Cody; Annie D Cohen; Dana L Tudorascu; Charles K Stone; Julie C Price; Sterling C Johnson; William E Klunk; Bradley T Christian

doi:10.1007/s11682-018-9888-y

Imaging neurodegeneration in Down syndrome: brain templates for amyloid burden and tissue segmentation

Brain Imaging Behav. 2019 Apr;13(2):345-353. doi: 10.1007/s11682-018-9888-y.

Authors

Patrick J Lao^{1

2}, Ben L Handen^{3

4

5

6}, Tobey J Betthauser^{7

8}, Karly A Cody⁸, Annie D Cohen³, Dana L Tudorascu^{3

9

10}, Charles K Stone¹¹, Julie C Price^{12

13}, Sterling C Johnson¹⁴, William E Klunk^{3

15}, Bradley T Christian^{7

8

16}

Affiliations

¹ Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI, 53705, USA. plao@wisc.edu.
² Waisman Center, University of Wisconsin-Madison, 1500 Highland Ave, Madison, WI, 53705, USA. plao@wisc.edu.
³ Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
⁴ Department of Pediatrics, University of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.
⁵ Department of Psychology, University of Pittsburgh, 201 South Bouquet Street, Pittsburgh, PA, 15260, USA.
⁶ Department of Instruction and Learning, University of Pittsburgh, 230 South Bouquet Street, Pittsburgh, PA, 15260, USA.
⁷ Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI, 53705, USA.
⁸ Waisman Center, University of Wisconsin-Madison, 1500 Highland Ave, Madison, WI, 53705, USA.
⁹ Department of Internal Medicine, University of Pittsburgh, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
¹⁰ Department of Biostatistics, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA, 15261, USA.
¹¹ Department of Cardiovascular Medicine, University of Wisconsin-Madison, 1 South Park Street, Madison, WI, 53715, USA.
¹² Department of Radiology, University of Pittsburgh, 3600 Forbes @ Meyran Avenues, Pittsburgh, PA, 15213, USA.
¹³ Department of Radiology, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, 02129, USA.
¹⁴ Department of Medicine-Geriatrics, University of Wisconsin-Madison, 1685 Highland Ave, Madison, WI, 53705, USA.
¹⁵ Department of Neurology, University of Pittsburgh, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA.
¹⁶ Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Blvd, Madison, WI, 53719, USA.

Abstract

The focus of Alzheimer's disease (AD) neuroimaging research has shifted towards an investigation of the earliest stages of AD pathogenesis, which manifests in every young adult with Down syndrome (DS; trisomy 21) resulting from a deterministic genetic predisposition to amyloid precursor protein overproduction. Due to morphological differences in brain structure in the DS population, special consideration must be given to processing pipelines and the use of normative atlases developed for the non-DS population. Further, the use of typical MRI to MRI template spatial normalization is less desirable in this cohort due to a greater presence of motion artefacts in MRI images. The diffuse nature of PiB uptake and comparatively lower spatial resolution of the PET image permits the purposing of this modality as a template for spatial normalization, which can substantially improve the robustness of this procedure in the cases of MRI images with motion. The aim of this work was to establish standardized methods for spatial normalization and tissue type segmentation using DS specific templates in order to perform voxel-wise analyses. A total of 72 adults with DS underwent [¹¹C]PiB PET to assess brain amyloid burden and volumetric MRI imaging. A DS specific PiB template for spatial normalization and a set of DS specific prior probability templates were created with two-pass methods. With implementation of this DS specific PiB template, no participants were excluded due to poor spatial normalization, thus maximizing the sample size for PiB analyses in standardized space. In addition, difference images between prior probability templates created from the general population and the DS population reflected known morphological differences, particularly in the frontal cortex. In conclusion, DS specific templates that account for unique challenges improve spatial normalization and tissue type segmentation, and provide a framework for reliable voxel-wise analysis of AD biomarkers in this atypical population.

Keywords: Alzheimer’s disease; Brain template; Down syndrome; MRI; PET.

MeSH terms

Adult
Brain / pathology
Down Syndrome / diagnostic imaging*
Down Syndrome / physiopathology
Female
Humans
Magnetic Resonance Imaging / methods*
Magnetic Resonance Imaging / standards
Male
Plaque, Amyloid / diagnostic imaging*
Positron-Emission Tomography / methods*
Positron-Emission Tomography / standards
Radiopharmaceuticals

Substances

Radiopharmaceuticals

Abstract

MeSH terms

Substances

Grants and funding