Dedicated container for postmortem human brain ultra-high field magnetic resonance imaging.

BACKGROUND: The emerging field of ultra-high field MRI (UHF-MRI, 7 Tesla and higher) provides the opportunity to image human brains at a higher resolution and with higher signal-to-noise ratios compared to the more widely available 1.5 and 3T scanners. Scanning postmortem tissue additionally allows for greatly increased scan times and fewer movement issues leading to improvements in image quality. However, typical postmortem neuroimaging routines involve placing the tissue within plastic bags that leave room for susceptibility artifacts from tissue-air interfaces, inadequate submersion, and leakage issues. To address these challenges in postmortem imaging, a custom-built nonferromagnetic container was developed that allows whole brain hemispheres to be scanned at sub-millimeter resolution within typical head-coils. METHOD: The custom-built polymethylmethacrylaat container consists of a cylinder with a hemispheric side and a lid with valves on the adjacent side. This shape fits within common MR head-coils and allows whole hemispheres to be submerged and vacuum sealed within it reducing imaging artifacts that would otherwise arise at air-tissue boundaries. Two hemisphere samples were scanned on a Siemens 9.4T Magnetom MRI scanner. High resolution T2* weighted data was obtained with a custom 3D gradient echo (GRE) sequence and diffusion-weighted imaging (DWI) scans were obtained with a 3D kT-dSTEAM sequence along 48 directions. RESULTS: The custom-built container proved to submerge and contain tissue samples effectively and showed no interferences with MR scanning acquisition. The 3D GRE sequence provided high resolution isotropic T2* weighted data at 250 µm which showed a clear visualization of gray and white matter structures. DWI scans allowed for dense reconstruction of structural white matter connections via tractography. CONCLUSION: Using this custom-built container worked towards achieving high quality MR images of postmortem brain material. This procedure can have advantages over traditional schemes including utilization of a standardized protocol and the reduced likelihood of leakage. This methodology could be adjusted and used to improve typical postmortem imaging routines.

Nigral neuropathology of Parkinson's motor subtypes coincide with circuitopathies: a scoping review.

The neuropathological substrates of Parkinson's disease (PD) patients with motor subtypes tremor-dominance (TD), non-tremor dominance (nTD), postural instability and gait difficulty (PIGD), and akinetic-rigid (AR) are not completely differentiated. While extensive pathological research has been conducted on neuronal tissue of PD patients, data have not been discussed in the context of mechanistic circuitry theories differentiating motor subtypes. It is, therefore, expected that a more specific and tailored management of PD symptoms can be accomplished by understanding symptom-specific neuropathological mechanisms with the detail histology can provide. This scoping review gives an overview of the literature comparing TD and nTD PD motor subtypes by clarify observed pathology with underlying physiological circuitry theories. Studies using an array of pathological examination techniques have shown significant differences between TD and nTD PD subtypes. nTD PD patients show higher neuronal loss, gliosis, extraneuronal melanin deposits, and neuroaxonal dystrophy in multiple subregions of the substantia nigra (SN) related to the overactivity of the indirect motor loop. TD patients show more severe cell loss specifically in medial SN subdivisions, and have damage in the retrorubral field A-8 that projects to the dorsolateral striatum and ventromedial thalamus in the direct motor loop. Pathological studies are consistent with neuroimaging data and support contemporary mechanistic circuitry theories of PD motor symptom genesis. Further multimodal neuroimaging and histological studies are required to validate and expand upon these findings.

The role of neurotransmitter systems in mediating deep brain stimulation effects in Parkinson's disease.

Deep brain stimulation (DBS) is among the most successful paradigms in both translational and reverse translational neuroscience. DBS has developed into a standard treatment for movement disorders such as Parkinson's disease (PD) in recent decades, however, specific mechanisms behind DBS's efficacy and side effects remain unrevealed. Several hypotheses have been proposed, including neuronal firing rate and pattern theories that emphasize the impact of DBS on local circuitry but detail distant electrophysiological readouts to a lesser extent. Furthermore, ample preclinical and clinical evidence indicates that DBS influences neurotransmitter dynamics in PD, particularly the effects of subthalamic nucleus (STN) DBS on striatal dopaminergic and glutamatergic systems; pallidum DBS on striatal dopaminergic and GABAergic systems; pedunculopontine nucleus DBS on cholinergic systems; and STN-DBS on locus coeruleus (LC) noradrenergic system. DBS has additionally been associated with mood-related side effects within brainstem serotoninergic systems in response to STN-DBS. Still, addressing the mechanisms of DBS on neurotransmitters' dynamics is commonly overlooked due to its practical difficulties in monitoring real-time changes in remote areas. Given that electrical stimulation alters neurotransmitter release in local and remote regions, it eventually exhibits changes in specific neuronal functions. Consequently, such changes lead to further modulation, synthesis, and release of neurotransmitters. This narrative review discusses the main neurotransmitter dynamics in PD and their role in mediating DBS effects from preclinical and clinical data.

Neuroimaging Detectable Differences between Parkinson's Disease Motor Subtypes: A Systematic Review.

BACKGROUND: The neuroanatomical substrates of Parkinson's disease (PD) with tremor-dominance (TD) and those with non-tremor dominance (nTD), postural instability and gait difficulty (PIGD), and akinetic-rigid (AR) are not fully differentiated. A better understanding of symptom specific pathoanatomical markers of PD subtypes may result in earlier diagnosis and more tailored treatment. Here, we aim to give an overview of the neuroimaging literature that compared PD motor subtypes. METHODS: A systematic literature review on neuroimaging studies of PD subtypes was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search terms submitted to the PubMed database included: "Parkinson's disease", "MRI" and "motor subtypes" (TD, nTD, PIGD, AR). The results are first discussed from macro to micro level of organization (i.e., (1) structural; (2) functional; and (3) molecular) and then by applied imaging methodology. FINDINGS: Several neuroimaging methods including diffusion imaging and positron emission tomography (PET) distinguish specific PD motor subtypes well, although findings are mixed. Furthermore, our review demonstrates that nTD-PD patients have more severe neuroalterations compared to TD-PD patients. More specifically, nTD-PD patients have deficits within striato-thalamo-cortical (STC) circuitry and other thalamocortical projections related to cognitive and sensorimotor function, while TD-PD patients tend to have greater cerebello-thalamo-cortical (CTC) circuitry dysfunction. CONCLUSIONS: Based on the literature, STC and CTC circuitry deficits seem to be the key features of PD and the subtypes. Future research should make greater use of multimodal neuroimaging and techniques that have higher sensitivity in delineating subcortical structures involved in motor diseases.