The generation of tetrahedral mesh models for neuroanatomical MRI

In this article, we describe a detailed method for automatically generating tetrahedral meshes from 3D images having multiple region labels. An adaptively sized tetrahedral mesh modeling approach is described that is capable of producing meshes conforming precisely to the voxelized regions in the image. Efficient tetrahedral mesh improvement is then performed minimizing an energy function containing three terms: a smoothing term to remove the voxelization, a fidelity term to maintain continuity with the image data, and a novel elasticity term to prevent the tetrahedra from becoming flattened or inverted as the mesh deforms while allowing the voxelization to be removed entirely. The meshing algorithm is applied to structural MR image data that has been automatically segmented into 56 neuroanatomical sub-divisions as well as on two other examples. The resulting tetrahedral representation has several desirable properties such as tetrahedra with dihedral angles away from 0 and 180 degrees, smoothness, and a high resolution. Tetrahedral modeling via the approach described here has applications in modeling brain structure in normal as well as diseased brain in human and non-human data and facilitates examination of 3D object deformations resulting from neurological illness (e.g. Alzheimer's disease), development, and/or aging.     

Combination of interfragmentary screws and locking plates in distal meta-diaphyseal fractures of the tibia: a retrospective, single-centre pilot study

If distal tibia fractures cannot be treated with intramedullary nails, locking compression plates, such as the LCP Medial Distal Tibia Plate of Synthes, are used. Bridge plating with interfragmentary movement is the strategy for such osteosynthesis. Interfragmentary movement is difficult to predict. Too much movement leads to formation of more, but less stable callus; longer time until complete fracture healing has been reported. Interfragmentary movement can be controlled by the stability and flexibility of the osteosynthesis construct. We used interfragmentary screws to limit interfragmentary movement in certain cases. We noticed a tendency of faster fracture healing in patients with interfragment lag screw compared with those with sole bridge plating. We therefore retrospectively assessed our patients for time until clinical fracture healing (i.e., pain-free weight bearing and visible callus in both layers on conventional plain film radiographs) and callus formation.

Methods

Data (from patient chart and from regular visits) of 52 patients with fracture of the distal tibia were reviewed, of which 11 were lost to follow-up. After surgery, weight bearing was limited to 20 kg for 6 weeks and then increased in weekly intervals to the pain threshold. X-rays were taken after 3 days, 6, 12 and 24 weeks and when achieving full weight bearing. Time from surgery until ability to full weight bearing was measured and compared. Callus index was measured as quotient of callus thickness and diameter of corticalis both in a.p. and sagittal direction. Statistical evaluation was done with the Mann–Whitney U-test.

Results

A total of 41 patients could be analysed; of them, 30 patients had extra-articular fractures. Four patients had 43-B and seven patients had 43-C fractures.As many as 13/30 extra-articular fractures were treated with interfragmentary screws: In this group (n = 11, without considering one patient with plate failure and one with pseudarthrosis) time to full weight bearing was 11.38 weeks versus 14.9 weeks without screw (n = 14; without two pseudarthrosis and one deep infection) (p = 0.044). Callus index at full weight bearing was significantly lesser in patients with screw compared with those without.

Conclusion

Though interfragmentary screws seem to block necessary interfragmentary movement, we see callus formation as a sign of secondary fracture healing. The osteosynthesis construct with interfragmentary screw seems to be more stable and less flexible than sole bridge plating, leading to faster fracture healing. Interfragmentary screws might help to control and limit interfragmentary movement in certain cases.     

Can high resolution manometry parameters for achalasia be obtained by conventional manometry?

High resolution manometry(HRM) is a new technology that made important contributions to the field of gastrointestinal physiology. HRM showed clear advan-tages over conventional manometry and it allowed the creation of different manometric parameters. On the other side, conventional manometry is still wild available. It must be better studied if the new technology made possible the creation and study of these parameters or if they were always there but the colorful intuitive panoramic view of the peristalsis from the pharynx to the stomach HRM allowed the human eyes to distinguish subtle parameters unknown or uncomprehend so far and if HRM parameters can be reliably obtained by conventional manometry and data from conventional manometry still can be accepted in achalasia studies. Conventional manometry relied solely on the residual pressure to evaluate lower esophageal sphincter(LES) relaxation while HRM can obtain the Integrated Relaxation Pressure. Esophageal body HRM parameters defines achalasia subtypes, the Chicago classification, based on esophageal pressurization after swallows. The characterization of each subtype is very intuitive by HRM but also easy by conventional manometry since only wave amplitudes need to be measured. In conclusion, conventional manometry is still valuable to classify achalasia according to the Chicago classification. HRM permits a better study of the LES.     

Antiviral treatment normalizes neurophysiological but not movement abnormalities in simian immunodeficiency virus-infected monkeys

Simian immunodeficiency virus (SIV) infection of rhesus monkeys provides an excellent model of the central nervous system (CNS) consequences of HIV infection. To discern the relationship between viral load and abnormalities induced in the CNS by the virus, we infected animals with SIV and later instituted antiviral treatment to lower peripheral viral load. Measurement of sensory-evoked potentials, assessing CNS neuronal circuitry, revealed delayed latencies after infection that could be reversed by lowering viral load. Cessation of treatment led to the reappearance of these abnormalities. In contrast, the decline in general motor activity induced by SIV infection was unaffected by antiviral treatment. An acute increase in the level of the chemokine monocyte chemoattractant protein-1 (MCP-1) was found in the cerebrospinal fluid (CSF) relative to plasma in the infected animals at the peak of acute viremia, likely contributing to an early influx of immune cells into the CNS. Examination of the brains of the infected animals after return of the electrophysiological abnormalities revealed diverse viral and inflammatory findings. Although some of the physiological abnormalities resulting from SIV infection can be at least temporarily reversed by lowering viral load, the viral-host interactions initiated by infection may result in long-lasting changes in CNS-mediated functions.     

Personalized medicine approach for optimizing the dose of tafamidis to potentially ameliorate wild-type transthyretin amyloidosis (cardiomyopathy)

Placebo-controlled clinical trials are useful for identifying the dose of a drug candidate that produces a meaningful clinical response in a patient population. Currently, Pfizer, Inc. is enrolling a 400-person clinical trial to test the efficacy of 20 or 80?mg of tafamidis to ameliorate transthyretin (TTR)-associated cardiomyopathy using clinical endpoints. Herein, we provide guidance for how to optimize the dose of tafamidis for each WT TTR cardiomyopathy patient using its mechanism of action as the key readout, i.e. we identify the dose of tafamidis that maximally kinetically stabilizes TTR in the blood. Tetramer dissociation is rate limiting for TTR aggregation, which appears to drive the pathology of the TTR amyloidoses. Hence, we measure the TTR tetramer dissociation rate (kinetic stability) in the patient's plasma as a function of tafamidis dose to optimize the dose employed to maximize kinetic stability. Historical data tell us that a subset of patients exhibiting higher tafamidis plasma concentrations are maximally kinetically stabilized at the 20-mg tafamidis dose, whereas the patient studied herein required a 60?mg once daily dose to achieve maximum kinetic stabilization. We anticipate that establishing the dose of tafamidis that achieves maximal TTR kinetic stabilization will translate into a maximal clinical effect, but that remains to be demonstrated.

Trial registration: ClinicalTrials.gov identifier: NCT01994889.