scholarly journals Detection of axonal degeneration in a mouse model of Huntington’s disease: comparison between diffusion tensor imaging and anomalous diffusion metrics

2019 ◽  
Vol 32 (4) ◽  
pp. 461-471 ◽  
Author(s):  
Rodolfo G. Gatto ◽  
Allen Q. Ye ◽  
Luis Colon-Perez ◽  
Thomas H. Mareci ◽  
Anna Lysakowski ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Anomalous Diffusion ◽  
Axonal Degeneration ◽  
Diffusion Tensor

scholarly journals Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington’s Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

2021 ◽  
Author(s):  
Danielle A. Simmons ◽  
Brian D. Mills ◽  
Robert R. Butler III ◽  
Jason Kuan ◽  
Tyne L. M. McHugh ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Treatment Response ◽  
Diffusion Tensor ◽  
Disease Onset ◽  
Therapeutic Effects ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Pharmacodynamic Biomarkers

AbstractHuntington’s disease (HD) is caused by an expansion of the CAG repeat in the huntingtin gene leading to preferential neurodegeneration of the striatum. Disease-modifying treatments are not yet available to HD patients and their development would be facilitated by translatable pharmacodynamic biomarkers. Multi-modal magnetic resonance imaging (MRI) and plasma cytokines have been suggested as disease onset/progression biomarkers, but their ability to detect treatment efficacy is understudied. This study used the R6/2 mouse model of HD to assess if structural neuroimaging and biofluid assays can detect treatment response using as a prototype the small molecule p75NTR ligand LM11A-31, shown previously to reduce HD phenotypes in these mice. LM11A-31 alleviated volume reductions in multiple brain regions, including striatum, of vehicle-treated R6/2 mice relative to wild-types (WTs), as assessed with in vivo MRI. LM11A-31 also normalized changes in diffusion tensor imaging (DTI) metrics and diminished increases in certain plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6, in R6/2 mice. Finally, R6/2-vehicle mice had increased urinary levels of the p75NTR extracellular domain (ecd), a cleavage product released with pro-apoptotic ligand binding that detects the progression of other neurodegenerative diseases; LM11A-31 reduced this increase. These results are the first to show that urinary p75NTR-ecd levels are elevated in an HD mouse model and can be used to detect therapeutic effects. These data also indicate that multi-modal MRI and plasma cytokine levels may be effective pharmacodynamic biomarkers and that using combinations of these markers would be a viable and powerful option for clinical trials.

G08 A multicentre approach for the detection of patterns of impairment in Huntington's disease by using diffusion tensor imaging

2012 ◽  
Vol 83 (Suppl 1) ◽  
pp. A28.3-A29
Author(s):  
H-P Mueller ◽  
R Sprengelmeyer ◽  
SD Süssmuth ◽  
G Groen ◽  
NZ Hobbs ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor

Regional white matter change in pre-symptomatic Huntington's disease: A diffusion tensor imaging study

2005 ◽  
Vol 140 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Sarah A.J. Reading ◽  
Michael A. Yassa ◽  
Arnold Bakker ◽  
Adam C. Dziorny ◽  
Lisa M. Gourley ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Imaging Study ◽  
White Matter Change ◽  
Diffusion Tensor Imaging Study

scholarly journals Test-Retest Reliability of Diffusion Tensor Imaging in Huntington’s Disease

PLoS Currents ◽  
2014 ◽  
Author(s):  
James H. Cole ◽  
Ruth E. Farmer ◽  
Elin M. Rees ◽  
Hans J. Johnson ◽  
Chris Frost ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Retest Reliability ◽  
Test Retest Reliability

A complementary diffusion tensor imaging (DTI)-histological study in a model of Huntington's disease

2012 ◽  
Vol 33 (5) ◽  
pp. 945-959 ◽  
Author(s):  
Nadja Van Camp ◽  
Ines Blockx ◽  
Lluïsa Camón ◽  
Nuria de Vera ◽  
Marleen Verhoye ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Histological Study ◽  
Diffusion Tensor Imaging Dti

A longitudinal diffusion tensor imaging study in symptomatic Huntington's disease

2009 ◽  
Vol 81 (3) ◽  
pp. 257-262 ◽  
Author(s):  
A. Sritharan ◽  
G. F Egan ◽  
L. Johnston ◽  
M. Horne ◽  
J. L Bradshaw ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Imaging Study ◽  
Longitudinal Diffusion ◽  
Diffusion Tensor Imaging Study

scholarly journals Longitudinal Diffusion Tensor Imaging Shows Progressive Changes in White Matter in Huntington’s Disease

2015 ◽  
Vol 4 (4) ◽  
pp. 333-346 ◽  
Author(s):  
Sarah Gregory ◽  
James H. Cole ◽  
Ruth E. Farmer ◽  
Elin M. Rees ◽  
Raymund A.C. Roos ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Diffusion Tensor ◽  
Longitudinal Diffusion

scholarly journals Correlation between Relaxometry and Diffusion Tensor Imaging in the Globus Pallidus of Huntington’s Disease Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0118907 ◽  
Author(s):  
Michael Syka ◽  
Jiří Keller ◽  
Jiří Klempíř ◽  
Aaron M. Rulseh ◽  
Jan Roth ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Globus Pallidus ◽  
Diffusion Tensor ◽  
And Diffusion

Diffusion Tensor Imaging in Preclinical and Human Studies of Huntington’s Disease: What Have we Learned so Far?

2019 ◽  
Vol 15 (6) ◽  
pp. 521-542 ◽  
Author(s):  
Rodolfo Gabriel Gatto ◽  
Carina Weissmann
Keyword(s):  
Diffusion Tensor Imaging ◽  
Animal Models ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Clinical Studies ◽  
Animal Studies ◽  
Grey Matter ◽  
Diffusion Tensor ◽  
Ultrastructural Changes

Background:Huntington’s Disease is an irreversible neurodegenerative disease characterized by the progressive deterioration of specific brain nerve cells. The current evaluation of cellular and physiological events in patients with HD relies on the development of transgenic animal models. To explore such events in vivo, diffusion tensor imaging has been developed to examine the early macro and microstructural changes in brain tissue. However, the gap in diffusion tensor imaging findings between animal models and clinical studies and the lack of microstructural confirmation by histological methods has questioned the validity of this method.Objective:This review explores white and grey matter ultrastructural changes associated to diffusion tensor imaging, as well as similarities and differences between preclinical and clinical Huntington’s Disease studies.Methods:A comprehensive review of the literature using online-resources was performed (Pub- Med search).Results:Similar changes in fractional anisotropy as well as axial, radial and mean diffusivities were observed in white matter tracts across clinical and animal studies. However, comparative diffusion alterations in different grey matter structures were inconsistent between clinical and animal studies.Conclusion:Diffusion tensor imaging can be related to specific structural anomalies in specific cellular populations. However, some differences between animal and clinical studies could derive from the contrasting neuroanatomy or connectivity across species. Such differences should be considered before generalizing preclinical results into the clinical practice. Moreover, current limitations of this technique to accurately represent complex multicellular events at the single micro scale are real. Future work applying complex diffusion models should be considered.

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