Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease.

Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer's disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer's disease.

In vivo imaging of tau pathology using multi-parametric quantitative MRI.

As the number of people diagnosed with Alzheimer's disease (AD) reaches epidemic proportions, there is an urgent need to develop effective treatment strategies to tackle the social and economic costs of this fatal condition. Dozens of candidate therapeutics are currently being tested in clinical trials, and compounds targeting the aberrant accumulation of tau proteins into neurofibrillary tangles (NFTs) are the focus of substantial current interest. Reliable, translatable biomarkers sensitive to both tau pathology and its modulation by treatment along with animal models that faithfully reflect aspects of the human disease are urgently required. Magnetic resonance imaging (MRI) is well established as a valuable tool for monitoring the structural brain changes that accompany AD progression. However the descent into dementia is not defined by macroscopic brain matter loss alone: non-invasive imaging measurements sensitive to protein accumulation, white matter integrity and cerebral haemodynamics probe distinct aspects of AD pathophysiology and may serve as superior biomarkers for assessing drug efficacy. Here we employ a multi-parametric array of five translatable MRI techniques to characterise the in vivo pathophysiological phenotype of the rTg4510 mouse model of tauopathy (structural imaging, diffusion tensor imaging (DTI), arterial spin labelling (ASL), chemical exchange saturation transfer (CEST) and glucose CEST). Tau-induced pathological changes included grey matter atrophy, increased radial diffusivity in the white matter, decreased amide proton transfer and hyperperfusion. We demonstrate that the above markers unambiguously discriminate between the transgenic group and age-matched controls and provide a comprehensive profile of the multifaceted neuropathological processes underlying the rTg4510 model. Furthermore, we show that ASL and DTI techniques offer heightened sensitivity to processes believed to precede detectable structural changes and, as such, provides a platform for the study of disease mechanisms and therapeutic intervention.

Cast-bracing of femoral fractures: experience at emory university hospitals.

At Emory University Hospitals from 1975 to 1979, 110 fractures of the femoral shaft were treated following a femoral fracture protocol with a single component cast-brace and early ambulation. In an effort to reduce the hospitalization and disability time in patients with mid-third and distal-third femoral fractures, a technique of modified Dehne bracing was used in which immediate ambulation was instituted after casting. Prior to initiation of this protocol, these fractures were routinely treated with six to eight weeks of balanced traction, followed by four to six months of cast fixation and a subsequent period of rehabilitation. Complications of the technique occurred in 9% of the patients, with shortening of 2.3 cm in 5%, refractures in 3% and malunion in 1%.This series of patients demonstrates the technical feasibility of a single component cast-brace and early ambulation for fractures of the femoral shaft, which is a great advance in the closed treatment of femoral fractures. Our results show that early cast-bracing using a modified Dehne technique is a viable method of treating fractures of the femoral shaft, with the technique being most effective when applied in the early stages- days one through 28. Indexing terms: cast-bracing, femoral fractures.

The Pennsylvania Plan. An algorithm for the management of lumbar degenerative disc disease.

An algorithm for the sequential management of the patient with low-back pain has been formulated from evaluation of treatment outcomes. Patients presenting with back pain complaints and cauda equina syndrome are evaluated with immediate myelography. Without this complication, back pain patients are treated with 6 weeks of conservative therapy. Those who fail to respond are evaluated with progressively more complex techniques. When sciatica predominates, treatment may ultimately include laminectomy. When back pain predominates, medical and psychosocial appraisal are recommended. Some with normal medical and psychosocial evaluations may become candidates for spine fusion. The remaining are treated according to the findings of such appraisals. Rigorous screening is mandatory prior to any surgery.