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Ivan Klyuzhin

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2 papers

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YNICL Journal 2019 Journal Article

Joint pattern analysis applied to PET DAT and VMAT2 imaging reveals new insights into Parkinson's disease induced presynaptic alterations

Jessie Fanglu Fu
Ivan Klyuzhin
Jessamyn McKenzie
Nicole Neilson
Elham Shahinfard
Katie Dinelle
Martin J. McKeown
A. Jon Stoessl

C]-MP (DAT marker) data from 15 early Parkinson's disease (PD) subjects; the behavior of these two tracers/targets is well characterized providing robust reference information for the method's outcome. Highly significant common subject profiles were identified that decomposed the characteristic dopaminergic changes into three distinct orthogonal spatial patterns: 1) disease-induced asymmetry between the less and more affected dorsal striatum; 2) disease-induced gradient with caudate and ventral striatum being relatively spared compared to putamen; 3) progressive loss in the less affected striatum, which correlated significantly with disease duration (p < 0.01 for DTBZ, p < 0.05 for MP). These common spatial patterns reproduce all known aspects of these two targets/tracers. In addition, orthogonality of the patterns may indicate different mechanisms underlying disease initiation or progression. Information unique to each tracer revealed a residual striatal asymmetry when targeting VMAT2, consistent with the notion that VMAT2 density is highly related to terminal degeneration; and a residual DAT disease-induced gradient in the striatum with relative DAT preservation in the substantia nigra. This finding may be indicative either of a possible DAT specific early disease compensation and/or related to disease origin. These results demonstrate the applicability and relevance of the joint pattern analysis approach to datasets obtained with two PET tracers; this data driven method, while recapitulating known aspects of the PD-induced tracer/target behaviour, was found to be statistically more robust and provided additional information on (i) correlated behaviors of the two systems, identified as orthogonal patterns, possibly reflecting different disease-induced alterations and (ii) system specific effects of disease. It is thus expected that this approach will be very well suited to the analysis of multi-tracer and/or multi-modality data and to relating the outcomes to different aspects of disease.

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YNICL Journal 2018 Journal Article

Investigation of serotonergic Parkinson's disease-related covariance pattern using [11C]-DASB/PET

Jessie Fanglu Fu
Ivan Klyuzhin
Shuying Liu
Elham Shahinfard
Nasim Vafai
Jessamyn McKenzie
Nicole Neilson
Rostom Mabrouk

We used positron emission tomography imaging with [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)- benzonitrile (DASB) and principal component analysis to investigate whether a specific Parkinson's disease (PD)-related spatial covariance pattern could be identified for the serotonergic system. We also explored if non-manifesting leucine-rich repeat kinase 2 (LRRK2) mutation carriers, with normal striatal dopaminergic innervation as measured with [11C]-dihydrotetrabenazine (DTBZ), exhibit a distinct spatial covariance pattern compared to healthy controls and subjects with manifest PD. 15 subjects with sporadic PD, eight subjects with LRRK2 mutation-associated PD, nine LRRK2 non-manifesting mutation carriers, and nine healthy controls participated in the study. The analysis was applied to the DASB non-displaceable binding potential values evaluated in 42 pre-defined regions of interest. PD was found to be associated with a specific spatial covariance pattern, comprising relatively decreased DASB binding in the caudate, putamen and substantia nigra and relatively preserved binding in the hypothalamus and hippocampus; the expression of this pattern in PD subjects was significantly higher than in healthy controls (P < 0. 001) and correlated significantly with disease duration (P < 0. 01) and with DTBZ binding in the more affected putamen (P < 0. 01). The LRRK2 non-manifesting mutation carriers expressed a different pattern, also significantly different from healthy controls (P < 0. 001), comprising relatively decreased DASB binding in the pons, pedunculopontine nucleus, thalamus and rostral raphe nucleus, and with relatively preserved binding in the hypothalamus, amygdala, hippocampus and substantia nigra. This pattern was not present in either sporadic or LRRK2 mutation-associated PD subjects. These findings, although obtained with a relatively limited number of subjects, suggest that specific and overall distinct spatial serotonergic patterns may be associated with PD and LRRK2 mutations. Alterations in regions where relative upregulation is observed in both patterns may be indicative of compensatory mechanisms preceding or protecting from disease manifestation.

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