Simultaneous, multidirectional acquisition of displacement fields in magnetic resonance elastography of the in vivo human brain

Purpose—To implement a multidirectional motion encoding scheme for magnetic resonance elastography (MRE) of the human brain with reduced acquisition time, and investigate its performance relative to a conventional MRE scheme. Materials and Methods—The sample interval modulation (SLIM) scheme was implemented in a multishot, variable density spiral MRE sequence. The brains of seven healthy volunteers were investigated with both SLIM-MRE and conventional MRE acquisitions in a single imaging session on a clinical 3 T MRI scanner with 50 Hz vibration. Following extraction of displacement fields, complex shear modulus property maps were estimated for each encoding acquisition. Results—The SLIM-MRE and conventional MRE acquisitions produced deformation fields that were nearly identical and exhibited an average correlation coefficient of 0.95 (all p < 0.05). Average properties of white matter differed between the two acquisitions by less than 5% for all volunteers, which is better than reproducibility estimates for conventional MRE alone. Conclusions—The use of SLIM provides very similar quantitative property estimates compared to the conventional MRE encoding scheme. The SLIM acquisition is 2.5 times faster than the conventional acquisition, and may improve the adoption of MRE in clinical settings

Analysis of YFP(J16)-R6/2 reporter mice and postmortem brains reveals early pathology and increased vulnerability of callosal axons in Huntington's disease.

Cumulative evidence indicates that the onset and severity of Huntington’s disease (HD) symptoms correlate with connectivity deficits involving specific neuronal populations within cortical and basal ganglia circuits. Brain imaging studies and pathological reports further associated these deficits with alterations in cerebral white matter structure and axonal pathology. However, whether axonopathy represents an early pathogenic event or an epiphenomenon in HD remains unknown, nor is clear the identity of specific neuronal populations affected. To directly evaluate early axonal abnormalities in the context of HD in vivo, we bred transgenic YFP(J16) with R6/2 mice, a widely used HD model. Diffusion tensor imaging and fluorescence microscopy studies revealed a marked degeneration of callosal axons long before the onset of motor symptoms. Accordingly, a significant fraction of YFP-positive cortical neurons in YFP(J16) mice cortex were identified as callosal projection neurons. Callosal axon pathology progressively worsened with age and was influenced by polyglutamine tract length in mutant huntingtin (mhtt). Degenerating axons were dissociated from microscopically visible mhtt aggregates and did not result from loss of cortical neurons. Interestingly, other axonal populations were mildly or not affected, suggesting differential vulnerability to mhtt toxicity. Validating these results, increased vulnerability of callosal axons was documented in the brains of HD patients. Observations here provide a structural basis for the alterations in cerebral white matter structure widely reported in HD patients. Collectively, our data demonstrate a dying-back pattern of degeneration for cortical projection neurons affected in HD, suggesting that axons represent an early and potentially critical target for mhtt toxicity