Imaging nigral pathology and clinical progression in Parkinson's disease

Abstract

Background The pattern of dopamine cell loss in Parkinson's disease is known to be prominent in the ventrolateral and caudal substantia nigra, but less severe in the dorsal and rostral region. Both diffusion tensor imaging and R2* relaxometry of the substantia nigra have been reported as potential markers for Parkinson's disease, but their relative ability to mark disease progression and differences in pathophysiological bases remains unclear. Methods High resolution T2-weigthed, R2*, and diffusion tensor imaging were obtained from 28 controls and 40 Parkinson's disease subjects [15 early-stage (disease duration≤1 year), 14 mid-stage (duration 2-5 years), and 11 late-stage (duration>5 years)]. Fractional anisotropy and R2* values in both rostral and caudal substantia nigra were obtained for all subjects, and clinical measures (disease duration; levodopa-equivalent daily dosage; “off”-drug Unified Parkinson's Disease Rating Scale motor score) were obtained for Parkinson's subjects. Results There was no correlation between fractional anisotropy and clinical measures, whereas R2* was strongly associated with disease progression. Compared to controls, fractional anisotropy in caudal substantia nigra was significantly decreased in Parkinson's disease patients of all stages, whereas in rostral substantia nigra it was decreased significantly only in the late-stage group. R2* in both substantia nigra regions was significantly increased in the mid-stage and late-stage, but not early-stage, of Parkinson's disease subjects. Conclusions These findings suggest that fractional anisotropy changes may mark early pathological changes in caudal substantia nigra, whereas the changes in R2* may more closely track Parkinson's disease's clinical progression after symptom onset.

T2* Relaxometry in Patients with Parkinson’s Disease

“…The atlas-based derived T2* values presented in this study (putamen, 34.2 ± 4.4; GPe, 23.5 ± 4.3; GPi, 23.4 ± 4.1; SN mean, 25.9 ± 6.5) were within the range of previously reported T2* values [5][6][7][8][9][10]. A multivariate ANOVA on the T2* relaxation times in the four specified anatomical regions as dependent variables did not show a significant main effect but a trend for the between-subject factor group (p = 0.071).…”

“…All studies investigating relaxation times to quantify in vivo the signal alterations of disease-specific areas in PD used manually drawn regions of interest (ROIs) [5][6][7][8][9][10]. An exact manual definition of a specific anatomical structure is time consuming.…”

Computational Dissection of Dopamine Motor and Motivational Functions in Humans

“…This translates into a gradient with stronger dopamine depletion in the dorsolateral putamen, compared to caudate and ventral striatum (Kish et al, 1988). The severity of motor symptoms in PD correlate with substantia nigra neurodegeneration (Gorell et al, 1995;Du et al, 2012) and with dopamine depletion in the dorsolateral striatum (Leenders et al, 1986), supporting involvement of the nigrostriatal pathway in motor dysfunction. In contrast, the ventral tegmental area has been hypothesized to play a key role in motivated behaviors (Tsai et al, 2009), through the mesolimbic projections to the ventral striatum (Berridge, 2007;Salamone et al, 2012), which has been conceived as a functional interface for translating motivational drives into motor or cognitive behaviors (Mogenson et al, 1980;Schmidt et al, 2012).…”

Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds”

“…32 To understand the stage-dependent changes of gyrification in PD, we subdivided PD patients into 3 subgroups as we have done previously. 33 The PD E upper limit of DOI (1 year) was chosen to define PD participants who had not received extended treatment. PD L was defined as PD participants having at least 5 years of disease duration for several reasons.…”