Diffusion Kurtosis Imaging Detects Microstructural Alterations
in Brain of alpha-Synuclein Overexpressing Transgenic Mouse
Model of Parkinson’s Disease: A Pilot Study

J 2015

Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alpha-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

KHAIRNAR, Amit Suresh, Peter LATTA, Eva DRAŽANOVÁ, Jana RUDÁ, Nikoletta SZABÓ et. al.

Basic information

Original name

Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alpha-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study

Name in Czech

Diffusion Kurtosis Imaging detekuje mikrostrukturální změny v mozku myší alfa-synukleinového transgenního modelu Parkinsonovy choroby: pilotní studie

Authors

KHAIRNAR, Amit Suresh (356 India, belonging to the institution), Peter LATTA (703 Slovakia, belonging to the institution), Eva DRAŽANOVÁ (203 Czech Republic, belonging to the institution), Jana RUDÁ (203 Czech Republic, belonging to the institution), Nikoletta SZABÓ (348 Hungary), Anas ARAB (760 Syrian Arab Republic, belonging to the institution), Birgit HUTTER-PAIER (40 Austria), Daniel HAVAS (40 Austria), Manfred WINDISCH (40 Austria), Alexandra ŠULCOVÁ (203 Czech Republic, belonging to the institution), Zenon STARČUK (203 Czech Republic, belonging to the institution) and Irena REKTOROVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Neurotoxicity research, New York, Springer, 2015, 1029-8428

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30000 3. Medical and Health Sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.140

RIV identification code

RIV/00216224:14740/15:00083366

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1007/s12640-015-9537-9

UT WoS

000362028700001

Keywords in English

Diffusion kurtosis imaging; a-Synuclein; TNWT-61; Parkinson’s disease; Transgenic mice; TBSS

Abstract

V originále

Evidence suggests that accumulation and aggregation of alpha-synuclein contribute to the pathogenesis of Parkinson's disease (PD). The aim of this study was to evaluate whether diffusion kurtosis imaging (DKI) will provide a sensitive tool for differentiating between alpha-synuclein-overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. This experiment was designed as a proof-of-concept study and forms a part of a complex protocol and ongoing translational research. Nine-month-old TNWT-61 mice and age-matched WT littermates underwent behavioral tests to monitor motor impairment and MRI scanning using 9.4 Tesla system in vivo. Tract-based spatial statistics (TBSS) and the DKI protocol were used to compare the whole brain white matter of TNWT-61 and WT mice. In addition, region of interest (ROI) analysis was performed in gray matter regions such as substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus known to show higher accumulation of alpha-synuclein. For the ROI analysis, both DKI (6 b-values) protocol and conventional (2 b-values) diffusion tensor imaging (cDTI) protocol were used. TNWT-61 mice showed significant impairment of motor coordination. With the DKI protocol, mean, axial, and radial kurtosis were found to be significantly elevated, whereas mean and radial diffusivity were decreased in the TNWT-61 group compared to that in the WT controls with both TBSS and ROI analysis. With the cDTI protocol, the ROI analysis showed decrease in all diffusivity parameters in TNWT-61 mice. The current study provides evidence that DKI by providing both kurtosis and diffusivity parameters gives unique information that is complementary to cDTI for in vivo detection of pathological changes that underlie PD-like symptomatology in TNWT-61 mouse model of PD. This result is a crucial step in search for a candidate diagnostic biomarker with translational potential and relevance for human studies.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

EE2.3.30.0009, research and development project

Name: Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci

Files attached

ZVV_2015_139_1306155_Diffusion_Kurtosis.pdf

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Citovat

KHAIRNAR, Amit Suresh, Peter LATTA, Eva DRAŽANOVÁ, Jana RUDÁ, Nikoletta SZABÓ, Anas ARAB, Birgit HUTTER-PAIER, Daniel HAVAS, Manfred WINDISCH, Alexandra ŠULCOVÁ, Zenon STARČUK and Irena REKTOROVÁ. Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alpha-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study. Neurotoxicity research. New York: Springer, 2015, vol. 28, No 4, p. 281-289. ISSN 1029-8428. Available from: https://dx.doi.org/10.1007/s12640-015-9537-9.

@article{1306155,
   author = {Khairnar, Amit Suresh and Latta, Peter and Dražanová, Eva and Rudá, Jana and Szabó, Nikoletta and Arab, Anas and HutterandPaier, Birgit and Havas, Daniel and Windisch, Manfred and Šulcová, Alexandra and Starčuk, Zenon and Rektorová, Irena},
   article_location = {New York},
   article_number = {4},
   doi = {http://dx.doi.org/10.1007/s12640-015-9537-9},
   keywords = {Diffusion kurtosis imaging; a-Synuclein; TNWT-61; Parkinson’s disease; Transgenic mice; TBSS},
   language = {eng},
   issn = {1029-8428},
   journal = {Neurotoxicity research},
   title = {Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alpha-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study},
   url = {http://link.springer.com/article/10.1007%2Fs12640-015-9537-9},
   volume = {28},
   year = {2015}
}

TY  - JOUR
ID  - 1306155
AU  - Khairnar, Amit Suresh - Latta, Peter - Dražanová, Eva - Rudá, Jana - Szabó, Nikoletta - Arab, Anas - Hutter-Paier, Birgit - Havas, Daniel - Windisch, Manfred - Šulcová, Alexandra - Starčuk, Zenon - Rektorová, Irena
PY  - 2015
TI  - Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alpha-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study
JF  - Neurotoxicity research
VL  - 28
IS  - 4
SP  - 281-289
EP  - 281-289
PB  - Springer
SN  - 10298428
KW  - Diffusion kurtosis imaging
KW  - a-Synuclein
KW  - TNWT-61
KW  - Parkinson’s disease
KW  - Transgenic mice
KW  - TBSS
UR  - http://link.springer.com/article/10.1007%2Fs12640-015-9537-9
L2  - http://link.springer.com/article/10.1007%2Fs12640-015-9537-9
N2  - Evidence suggests that accumulation and aggregation of alpha-synuclein contribute to the pathogenesis of Parkinson's disease (PD). The aim of this study was to evaluate whether diffusion kurtosis imaging (DKI) will provide a sensitive tool for differentiating between alpha-synuclein-overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. This experiment was designed as a proof-of-concept study and forms a part of a complex protocol and ongoing translational research. Nine-month-old TNWT-61 mice and age-matched WT littermates underwent behavioral tests to monitor motor impairment and MRI scanning using 9.4 Tesla system in vivo. Tract-based spatial statistics (TBSS) and the DKI protocol were used to compare the whole brain white matter of TNWT-61 and WT mice. In addition, region of interest (ROI) analysis was performed in gray matter regions such as substantia nigra, striatum, hippocampus, sensorimotor cortex, and thalamus known to show higher accumulation of alpha-synuclein. For the ROI analysis, both DKI (6 b-values) protocol and conventional (2 b-values) diffusion tensor imaging (cDTI) protocol were used. TNWT-61 mice showed significant impairment of motor coordination. With the DKI protocol, mean, axial, and radial kurtosis were found to be significantly elevated, whereas mean and radial diffusivity were decreased in the TNWT-61 group compared to that in the WT controls with both TBSS and ROI analysis. With the cDTI protocol, the ROI analysis showed decrease in all diffusivity parameters in TNWT-61 mice. The current study provides evidence that DKI by providing both kurtosis and diffusivity parameters gives unique information that is complementary to cDTI for in vivo detection of pathological changes that underlie PD-like symptomatology in TNWT-61 mouse model of PD. This result is a crucial step in search for a candidate diagnostic biomarker with translational potential and relevance for human studies.
ER  -

KHAIRNAR, Amit Suresh, Peter LATTA, Eva DRAŽANOVÁ, Jana RUDÁ, Nikoletta SZABÓ, Anas ARAB, Birgit HUTTER-PAIER, Daniel HAVAS, Manfred WINDISCH, Alexandra ŠULCOVÁ, Zenon STARČUK and Irena REKTOROVÁ. Diffusion Kurtosis Imaging Detects Microstructural Alterations in Brain of alpha-Synuclein Overexpressing Transgenic Mouse Model of Parkinson’s Disease: A Pilot Study. \textit{Neurotoxicity research}. New York: Springer, 2015, vol.~28, No~4, p.~281-289. ISSN~1029-8428. Available from: https://dx.doi.org/10.1007/s12640-015-9537-9.

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