Visualization of nigrosome 1 and its loss in PD: Pathoanatomical correlation and in vivo 7 T MRI.

Blazejewska AI, Schwarz ST, Pitiot A, Stephenson MC, Lowe J, Bajaj N, Bowtell RW, Auer DP, Gowland PA.
Neurology. 2013 Aug 6;81(6):534-40. PMID: 23843466
 

Objective:   Parkinson’s Disease (PD) is a progressive neurological disease marked by the loss of dopamine-producing cells in the midbrain area known as the substantia nigra (SN).  Diagnosis, and consequently therapy, usually occurs after pathognomonic motor symptoms occur, brought about by the loss of greater than 60% of the dopaminergic cells in the SN.  In this paper, diagnostic regions of the SN, known as nigrosomes, were examined by MRI in order to identify changes that could lead to earlier diagnosis of PD.

Results:

·         Areas defined by staining were able to be matched to and overlaid on MRI scans.  In the sample from the PD patient, the structure corresponding to nigrosome 1 (the area most affected by PD) could be seen on MRI, but lacked neuromelanin and staining for tyrosine hydroxylase (TH), two markers for the dopaminergic neurons in the SN.

·         The nigrosome 1 was examined in healthy volunteers with T2 weighted imaging with a 7T and a 3T scanner.  The 3T scanner could show the nigrosome, but with a lower-signal-to-noise ratio.  When compared to the nigrosome 1 of people suffering from PD, neuroradiologists blinded to the patients’ statuses could correctly classify their state of healthy in 7/8 controls and 10/10 of PD patients.

Conclusions:

·         The nigrosome 1 region of the SN can be accurately identified on a 7T MRI scanner using T2 weighted imaging.

·         Due to experimental design and small sample size, no definite conclusion can be drawn about this technique’s ability to identify PD patients before the onset of motor symptoms.  Longitudinal studies will be needed in populations being investigated for the progression of PD.

Methods:    Post-mortem human brains were acquired, formalin fixed, and imaged with a 7T MRI scanner.  The midbrains were then sectioned in to 5um slices for immunostaining.  Additional scans were done on live healthy controls and live patients with PD (diagnosed with traditional methods and shown to respond to standard therapy).  Further scans were done at 3T in order to investigate the feasibility of visualizing nigrosome 1 in a lower magnetic field.

-DH