Objective/Rationale:
The assessment of Parkinson’s disease is currently based on clinical symptoms that make an accurate diagnosis challenging, especially early on, when subtle impairment of movement begins. Likewise, progression of the disease and response to treatment can be difficult to predict. This study aims to establish objective markers of Parkinson’s disease based on magnetic resonance imaging (MRI) that allow accurate disease detection and reliable assessment of progression and response to treatment.
Project Description:
The study relies on established MRI technology but is unique in that it utilizes multiple MRI modalities to measure brain changes in PD, including structural MRI to detect loss of brain tissue, arterial spin labeling MRI to measure blood flow, diffusion tensor MRI to assess the integrity of nerve fibers, and susceptibility-weighted MRI to measure iron deposition. The primary goal is to test if these MRI modalities reveal a characteristic pattern of brain alterations in patients with PD and to correlate patterns with disease severity and progression. This goal will be accomplished by performing a prospective study with both clinical and MRI follow-up over one year on 30 subjects with a diagnosis of PD, 15 subjects with multiple system atrophy, and 20 healthy subjects for comparison.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
It is expected that this study will establish MRI-based measures that can be used to objectively aid in the early diagnosis of PD and to monitor disease progression. By providing objective and sensitive measures of PD detection and progression, multimodal MRI holds potential to considerably enhance the power of clinical trials to evaluate neuroprotection and disease-modifying effects of new pharmacologic interventions.
Anticipated Outcome:
It is anticipated that Parkinson’s disease is associated with regional alterations in the brain—including tissue loss, reduced blood flow, increased nerve fiber disintegration, and increased iron accumulation that are detectable using multimodal MRI. By using the various MRI modalities, the ability to measure brain pathology and disease progression in PD is likely improved compared to other methods that rely on only a single modality, enhancing the assessment of neuroprotective and disease-modifying trials of PD.
Progress Report
Preliminary results from 40 PD patients and 24 control subjects show PD is associated with abnormal values seen with susceptibility-weighted imaging (SWI), a measure for brain iron, and seen with diffusion tensor imaging (DTI), a measure for white matter integrity. In PD patients, SWI shows a pattern of regionally elevated iron levels and DTI detects a pattern of regional white matter degradation that involved structures of the known movement control circuit, such as the substantia nigra , the subthalamic nucleus and supplementary motor areas. Moreover, some of these measures correlate with severity of PD symptoms and also differ between tremor and akinetic-rigid dominant subtypes of the disease. Studies to determine the value of these MRI measures for predicting PD progression are ongoing. The preliminary findings suggest that SWI and DTI each detect a characteristic pattern of brain alterations in PD that could provide a marker for the disease. Efforts to study subjects with MSA have been slowed due to difficulties in recruitment.