Statistical parametric maps of 18F-FDG PET and 3-D autoradiography in the rat brain: a cross-validation study

Prieto, Elena; Collantes, María; Delgado, Mercedes; Juri, Carlos; Garcı́a-Garcı́a, Luis; Molinet, Francisco; Fernández-Valle, Encarnación; Pozo, Miguel A.; Gago, Belén; Martí-Climent, Josep M.; Obeso, José A.; Peñuelas, Iván

doi:10.1007/s00259-011-1905-y

Cited by 31 publications

(17 citation statements)

References 32 publications

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“…To overcome these problems in the present study an observer-independent wholebrain analysis was implemented using the reliable stereotactic normalization procedure of SPM. This allows quantitative voxel-based statistical analysis between time points and within groups (Prieto et al 2011). In future studies, accuracy of spatial localization may be controlled by application of autoradiography.…”

Section: Methodological Strengths and Limitationsmentioning

confidence: 99%

Sequential [18F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity

et al. 2014

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Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in brain glucose metabolism during behavioural recovery after surgical and chemical unilateral labyrinthectomy, to determine the extent and time-course of the involvement of different brain regions in vestibular compensation and test previously described hypotheses of underlying mechanisms. Systematic patterns of relative changes of glucose metabolism (rCGM) were observed during vestibular compensation. A significant asymmetry of rCGM appeared in the vestibular nuclei, vestibulocerebellum, thalamus, multisensory vestibular cortex, hippocampus and amygdala in the acute phase of vestibular imbalance (4 h). This was followed by early vestibular compensation over 1-2 days where rCGM re-balanced between the vestibular nuclei, thalami and temporoparietal cortices and bilateral rCGM increase appeared in the hippocampus and amygdala. Subsequently over 2-7 days, rCGM increased in the ipsilesional spinal trigeminal nucleus and later (7-9 days) rCGM increased in the vestibulocerebellum bilaterally and the hypothalamus and persisted in the hippocampus. These systematic dynamic rCGM patterns during vestibular compensation, were confirmed in a second rat model of chemical unilateral labyrinthectomy by serial [(18)F]FDG-µPET. These findings show that deafferentation-induced plasticity after unilateral labyrinthectomy involves early mechanisms of re-balancing predominantly in the brainstem vestibular nuclei but also in thalamo-cortical and limbic areas, and indicate the contribution of spinocerebellar sensory inputs and vestibulocerebellar adaptation at the later stages of behavioural recovery.

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Section: Methodological Strengths and Limitationsmentioning

confidence: 99%

Sequential [18F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity

et al. 2014

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“…While [ 18 F]FDOPA-PET can be used to image dopaminergic system integrity in the anaesthetised animal, [ 18 F]FDG uptake must occur in the awake state [ 14 ] as anaesthesia strongly decreases cerebral glucose metabolism [ 15 ]. Resting state [ 18 F]FDG-PET measurements were performed between days 13 and 24 after 6-OHDA injection.…”

Section: Methodsmentioning

confidence: 99%

Motor impairment and compensation in a hemiparkinsonian rat model: correlation between dopamine depletion severity, cerebral metabolism and gait patterns

et al. 2017

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BackgroundIn Parkinson’s disease (PD), cerebral dopamine depletion is associated with PD subtype-specific metabolic patterns of hypo- and hypermetabolism. It has been hypothesised that hypometabolism reflects impairment, while hypermetabolism may indicate compensatory activity. In order to associate metabolic patterns with pathophysiological and compensatory mechanisms, we combined resting state [18F]FDG-PET (to demonstrate brain metabolism in awake animals), [18F]FDOPA-PET (dopamine depletion severity) and gait analysis in a unilateral 6-hydroxydopamine rat model.ResultsWe found unilateral nigro-striatal dopaminergic loss to decrease swing speed of the contralesional forelimb and stride length of all paws in association with depletion severity. Depletion severity was found to correlate with compensatory changes such as increased stance time of the other three paws and diagonal weight shift to the ipsilesional hind paw. [18F]FDG-PET revealed ipsilesional hypo- and contralesional hypermetabolism; metabolic deactivation of the ipsilesional network needed for sensorimotor integration (hippocampus/retrosplenial cortex/lateral posterior thalamus) was solely associated with bradykinesia, but hypometabolism of the ipsilesional rostral forelimb area was related to both pathological and compensatory gait changes. Mixed effects were also found for hypermetabolism of the contralesional midbrain locomotor region, while contralesional striatal hyperactivation was linked to motor impairments rather than compensation.ConclusionsOur results indicate that ipsilesional hypo- and contralesional hypermetabolism contribute to both motor impairment and compensation. This is the first time when energy metabolism, dopamine depletion and gait analysis were combined in a hemiparkinsonian model. By experimentally increasing or decreasing compensational brain activity, its potential and limits can be further investigated.

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“…Rats were anesthetized with the same mixture of isoflurane and oxygen. The acquisition parameters and protocols have been described previously (Prieto et al, 2011).…”

Section: Micropet Scanning and Mri Acquisitionmentioning

confidence: 99%

Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: A longitudinal in-vivo study

Molinet-Dronda

Gago

Quiroga-Varela

et al. 2015

Neurobiology of Disease

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Carbon-11 labeled dihydrotetrabenazine ((11)C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied (11)C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague-Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. (11)C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new (11)C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). (11)C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between (11)C-DTBZ PET SB and striatal DAT immunostaining values (r=0.95, p<0.001). The data presented here indicate that (11)C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat.

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Statistical parametric maps of 18F-FDG PET and 3-D autoradiography in the rat brain: a cross-validation study

Cited by 31 publications

References 32 publications

Sequential [18F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity

Sequential [18F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity

Motor impairment and compensation in a hemiparkinsonian rat model: correlation between dopamine depletion severity, cerebral metabolism and gait patterns

Monoaminergic PET imaging and histopathological correlation in unilateral and bilateral 6-hydroxydopamine lesioned rat models of Parkinson's disease: A longitudinal in-vivo study

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