Browsing by Author "Baer K"

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    A Proof-of-Concept Solution for Co-locating 2D Histology Images in 3D for Histology-to-CT and MR Image Registration: Closing the Loop for Bone Sarcoma Treatment Planning.
    (Springer Nature, 2025-02-26) Phillips R; Zakkaroff C; Dittmer K; Robilliard N; Baer K; Butler A
    This work presents a proof-of-concept solution designed to facilitate more accurate radiographic feature characterisation in pre-surgical CT/MR volumes. The solution involves 3D co-location of 2D digital histology slides within ex-vivo, tumour tissue CT volumes. Initially, laboratory dissection measurements seed the placement of histology slices in corresponding CT volumes, followed by in-plane point-based registration of bone in histology images to the bone in CT. Validation using six bisected canine humerus ex-vivo CT datasets indicated a plane misalignment of 0.19 ± 1.8 mm. User input sensitivity was assessed at 0.08 ± 0.2 mm for plane translation and 0-1.6° deviation. These results show a similar magnitude of error to related prostate histology co-location work. Although demonstrated with a femoral canine sarcoma tumour, this solution can be generalised to various orthopaedic geometries and sites. It supports high-fidelity histology image co-location to improve understanding of tissue characterisation accuracy in clinical radiology. This solution requires only minimal adjustment to routine workflows. By integrating histology insights earlier in the presentation-diagnosis-planning-surgery-recovery loop, this solution guides data co-location to support the continued evaluation of safe pre-surgical margins.
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    Combined injection of rAAV with mannitol enhances gene expression in the rat brain
    (Cell Press, 6/09/2000) Mastakov M; Baer K; Xu R; Fitzsimons H; During M
    Recombinant adeno-associated viruses (rAAV) are highly efficient vectors for gene transfer into the central nervous system (CNS). However, a major hurdle for gene delivery to the mammalian brain is to achieve high-level transduction in target cells beyond the immediate injection site. Therefore, in addition to improvements in expression cassettes and viral titers, optimal injection parameters need to be defined. Here, we show that previous studies of somatic cell gene transfer to the mammalian brain have used suboptimal injection parameters, with even the lowest reported perfusion rates still excessively fast. Moreover, we evaluated the effect of local administration of mannitol to further enhance transgene expression and vector spread. Ultraslow microperfusion of rAAV, i.e., <33 nl/min, resulted in significantly higher gene expression and less injury of surrounding tissue than the previously reported rates of 100 nl/min or faster. Co-infusion of mannitol facilitated gene transfer to neurons, increasing both the total number and the distribution of transduced cells by 200-300%. Gene transfer studies in the CNS using rAAV should use very slow infusion rates and combined injection with mannitol to maximize transduction efficiency and spread.