Abstract
An MRI biomarker for Parkinsonism has long been sought, but almost all attempts at conventional field strengths have proved unsatisfactory, since patients and controls are not separated. The exception is Spin-Lattice Distribution MRI (SLD-MRI), a technique which detects changes in the substantia nigra (SN) due to changes in the spin-lattice relaxation time, T1. This easily separates patients with Parkinson's disease (PD) from control subjects at 1.5 Tesla, suggesting that it may be sensitive to presymptomatic disease. SLD-MRI demonstrates a topography of signal change within the SN which is the same as the known topography of pathological change, where the lateral portions of the nucleus are more affected than the medial. In a further step towards its validation, we apply SLD-MRI to a disease control, Progressive Supranuclear Palsy (PSP), the most common of the atypical forms of Parkinsonism. In PSP the topography of pathological change in the SN is reversed. We therefore hypothesized that PSP would show a topography of SLD-MRI signal change in the SN that is the reverse of PD (i.e. the medial portion is more affected than the lateral). All 7 patients showed such a topography of MR signal, and all patients were separated from control subjects. Although this is a step toward validation of SLD-MRI with respect to sensitivity and disease specificity, nevertheless we stress that this is a pilot project only. Validation will only be possible when comparing larger cohorts of PSP, PD and control subjects.
Highlights
MRI is known for its exquisite sensitivity to acute and subacute pathology
In Progressive Supranuclear Palsy (PSP) the largest signal change is seen medially, corresponding to the known pattern of pathologic change in PSP, opposite to that of Parkinson’s Disease (PD). This topography reflects the known topography of micropathological changes in the two conditions [10]
The null hypothesis, that control and PSP groups are indistinguishable is rejected for the RI and spin-lattice distribution index (SI) groups at a significance level p = 0.001
Summary
MRI is known for its exquisite sensitivity to acute and subacute pathology. This is because T2-weighted images are sensitive to small changes in the amount and character of water content in tissue. The existing techniques lack sensitivity and specificity for PD, and cannot reliably detect presymptomatic disease This has led to increasing efforts to investigate MRI at higher field strengths. We used the identical technique to image the SN in Progressive Supranuclear Palsy (PSP), a form of Parkinsonism where the topography of pathological change in the SN is known to be opposite to that in PD i.e. the medial portion of the nucleus being more affected than the lateral. First described in 1963, the most common of the atypical forms of Parkinson’s disease is usually referred to as PSP [8] It is a progressive, bradykinetic, adult-onset neurodegenerative disorder which superficially resembles PD. Using SLD-MRI we here validate the technique with respect to PSP as a disease control
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