In this project, we will focus on the use of ultra high field techniques (7T) for investigating the structural disorders of the brainstem and of the central deep nuclei in Parkinson’s disease (PD) and in Progressive Supranuclear Palsy (PSP), a rare parkinsonian syndrome, compared to normal age-matched subjects.
We specifically selected these 2 types of parkinsonian syndromes (PD and PSP) for the following reasons:
- In PSP, the occurrence of eye movement disorders or falls early in the course of the disease is the hallmark of the disease. PSP represents a paradigmatic disorder to study brainstem structures as the clinical disorders are mainly related to brainstem lesions that are well identified post mortem (severe neuronal loss in the PPN, lesions of the oculomotor system) (Litvan I et al 1996). Moreover, during the evolution of the disease eye movement recordings (EMR) may be altered before the detection of abnormal eye movements at bed-side examination (Rivaud-Pechoux S et al 2000). EMR parameters can be quantified and related to dysfunctions of specific well known brainstem oculomotor structures (superior colliculi, pontine and mesencephalic reticular formations, fastigial nucleus and nucleus raphe interpositus). Identification of some of these structures using neuroimaging may allow correlating neuronal loss with quantified abnormalities on EMR (video-graphy) (Rivaud-Pechoux et al 2000, 2007).
- In PD, pathology and neuronal loss occur beyond the dopaminergic system (Braak H et al 1996). Non dopaminergic lesions are considered being responsible (at least partially) for the occurrence of symptoms such RBD or gait and equilibrium disorders. RBD can be characterised using polysomnography and the locus sub-coeruleus is involved in the control of atonia during rapid eye movement (REM) sleep. Decreased signal intensity could be detected on 3T imaging in PD in the locus coeruleus (Shibata et al.2007). Whether the locus sub-coeruleus could be detected is questionable but, if so, it would be of particular interest as the occurrence of RBD exposes PD patients to 3 times more frequent hallucinations, and to cognitive disturbances (Postuma et al 2008). Gait and balance disorders are being a therapeutic challenge as their occurrence is negatively correlated to life expectancy and autonomy (Sinforiani et al 2008). In PD, early detection of lesions in the area of the PPN, prior to the occurrence of gait and balance difficulties may correlate with the occurrence of the symptoms later on.
At a later stage of the disease, as the PPN is a promising new target for DBS in parkinsonian patients with gait disturbance and postural instability refractory to other treatment modalities direct MRI localization of the PPN area and related structures may allow greater individual accuracy.
The goal of the project is to find new neuroimaging markers of deep brain nuclei in neurodegenerative diseases that can be used for the diagnosis of Parkinsonian syndromes at the early stage. In addition, the goal is the characterization of lesions of deep brain structures and the detection of biomarkers of neuronal lesions in PD that can be related to clinical signs, such as gait disorders.
Biomarkers of Parkinsonian syndromes could be used to create a diagnostic tool of the pathology and to correlate the identified markers with clinical signs.
As a whole, the structures that will be studied will be selected based on their scientific and clinical interest as previously detailed:
- In PD, there are no reliable imaging markers of substantia nigra (SN) pathology and nigro-striatal fiber pathways.
- Similarly, there are no markers of other deep brain nuclei involved in other Parkinsonian syndromes including the subthalamic nucleus (STN), the red nucleus (RN), oculomotor pathways (mesencephalic and pontine reticular formation, superior colliculli, implicated in eye-movement disorders in PSP), the pedonculo-pontine nucleus (involved in gait and posture control disorders) and the locus sub-coeruleus area (implicated in sleep disorders, located internal and ventral to the locus coeruleus and close to the brachium conjunctivum.
Some of the structures of interest in parkinsonian syndromes (thalamus, striatum, pallidum) can be observed using standard T1- or T2-weighted MR data. They can be more or less easily delineated, but no parcellation can be obtained. Many other structures located in the mesencephalon and the pons are difficult to see at the standard resolution of clinical data or do not depict any specific contrast, like the SN participating to motor control and severely damaged in Parkinsonian syndromes. In this project, we will use ultra high field systems (3T & 7T) to obtain very high spatial resolution images providing information about the localization, the morphometric characteristics (volume, shape), the subdivisions and the cytoarchitectonics of these structures.