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Jeffrey T Henderson

Publications and source records attributed to Jeffrey T Henderson.

5 recordsLinked to original sources

Eye-movement study and human performance using telepathology virtual slides: implications for medical education and differences with experience.

A core skill in diagnostic pathology is light microscopy. Remarkably little is known about human factors that affect the proficiency of pathologists as light microscopists. The cognitive skills of pathologists have received relatively little attention in comparison with the large literature on human performance studies in radiology. One reason for this lack of formal visual search studies in pathology has been the physical restrictions imposed by the close positioning of a microscope operator's head to the microscope's eyepieces. This blocks access to the operator's eyes and precludes assessment of the microscopist's eye movements. Virtual slide microscopy now removes this barrier and opens the door for studies on human factors and visual search strategies in light microscopy. The aim of this study was to assess eye movements of medical students, pathology residents, and practicing pathologists examining virtual slides on a digital display monitor. Whole histopathology glass slide digital images, so-called virtual slides, of 20 consecutive breast core biopsy cases were used in a retrospective study. These high-quality virtual slides were produced with an array-microscope equipped DMetrix DX-40 ultrarapid virtual slide processor (DMetrix, Tucson, Ariz). Using an eye-tracking device, we demonstrated for the first time that when a virtual slide reader initially looks at a virtual slide his or her eyes are very quickly attracted to regions of interest (ROIs) within the slide and that these ROIs are likely to contain diagnostic information. In a matter of seconds, critical decisions are made on the selection of ROIs for further examination at higher magnification. We recorded: (1) the time virtual slide readers spent fixating on self-selected locations on the video monitor; (2) the characteristics of the ways the eyes jumped between fixation locations; and (3) x and y coordinates for each virtual slide marking the sites the virtual slide readers manually selected for zooming to higher ROI magnifications. We correlated the locations of the visually selected fixation locations and the manually selected ROIs. Viewing profiles were identified for each group. Fully trained pathologists spent significantly less time (mean, 4.471 seconds) scanning virtual slides when compared to pathology residents (mean, 7.148 seconds) or medical students (mean, 11.861 seconds), but had relatively prolonged saccadic eye movements (P < .0001). Saccadic eye movements are defined as eye movements between fixation locations. On the other hand, the pathologists spent significantly more time than trainees dwelling on the 3 locations they subsequently chose for zooming. Unlike either the medical students or the residents, the pathologists frequently choose areas for viewing at higher magnification outside of areas of foveal (central) vision. Eye movement studies of scanning pathways (scan paths) may be useful for developing eye movement profiles for individuals and for understanding the difference in performances between novices and experts. They may also be useful for developing new visual search strategies for rendering diagnoses on telepathology virtual slides.

Biopsy↗

Neuroanatomical differences between mouse strains as shown by high-resolution 3D MRI.

The search for new mouse models of human disease requires a sensitive metric to make three-dimensional (3D) anatomical comparisons in a rapid and quantifiable manner. This is especially true in the brain, where changes in complex shapes such as the hippocampus and ventricles are difficult to assess with 2D histology. Here, we report that the 3D neuroanatomy of three strains of mice (129S1/SvImJ, C57/Bl6, and CD1) is significantly different from one another. Using image co-registration, we 'morphed' together nine brains of each strain scanned by magnetic resonance imaging at (60 microm)3 resolution to synthesize an average image. We applied three methods of comparison. First, we used visual inspection and graphically examined the standard deviation of the variability in each strain. Second, we annotated 42 neural structures and compared their volumes across the strains. Third, we assessed significant local deviations in volume and displacement between the two inbred strains, independent of prior anatomical knowledge.

Algorithms↗

Atm-null mice exhibit enhanced radiation-induced birth defects and a hybrid form of embryonic programmed cell death indicating a teratological suppressor function for ATM.

ATM (ataxia-telangiectasia mutated) is a genotoxic stress transducer. In this first report of Atm-dependent birth defects, Atm-null embryos were uniquely susceptible to low-dose (0.5 Gy) radiation, exhibiting severe runting, tail anomalies, and lethality, independent of cell cycle arrest or insulin-like growth factor 1. This treatment enhanced levels of p53 protein and central nervous system (CNS) apoptosis in wild-type mice, but not Atm-null mutants, at 6 h postirradiation. At 48 h, however, this pattern was reversed, with Atm-null mice exhibiting high levels of a hybrid form of programmed cell death within the CNS. Even heterozygous Atm-deficient embryos were radiosensitive to a higher radiation dose of 2 Gy. These results show that Atm is a novel teratologic suppressor gene protecting embryos from pathological cell death and teratogenesis initiated by even mild DNA damage.

Abnormalities, Radiation-Induced↗

Tetracycline-dependent regulation of formamidopyrimidine DNA glycosylase in transgenic mice conditionally reduces oxidative DNA damage in vivo.

8-Oxo-deoxyguanosine (8-oxo-dG) is a pervasive oxidative DNA lesion formed by endogenous oxidative stress and enhanced by drugs and environmental chemicals. This lesion results in transcriptional errors and mutations and is linked to neurodegeneration, teratogenesis, cancer, and other pathologies. We demonstrate that the neonatal central nervous system of transgenic mice carrying the tetracycline-regulable DNA repair gene formamidopyrimidine DNA glycosylase (fpg) has a 50% reduction in 8-oxo-dG levels. This enhanced DNA repair is suppressed by treatment with doxycycline. For the first time, this murine model permits the level of a specific DNA oxidation product to be regulated in a temporally and spatially specific manner, allowing its role as a primary or secondary factor in neurodegenerative disease to be determined in vivo.

8-Hydroxy-2'-Deoxyguanosine↗

Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB.

In the small intestine, the progeny of stem cells migrate in precise patterns. Absorptive, enteroendocrine, and goblet cells migrate toward the villus while Paneth cells occupy the bottom of the crypts. We show here that beta-catenin and TCF inversely control the expression of the EphB2/EphB3 receptors and their ligand ephrin-B1 in colorectal cancer and along the crypt-villus axis. Disruption of EphB2 and EphB3 genes reveals that their gene products restrict cell intermingling and allocate cell populations within the intestinal epithelium. In EphB2/EphB3 null mice, the proliferative and differentiated populations intermingle. In adult EphB3(-/-) mice, Paneth cells do not follow their downward migratory path, but scatter along crypt and villus. We conclude that in the intestinal epithelium beta-catenin and TCF couple proliferation and differentiation to the sorting of cell populations through the EphB/ephrin-B system.

Actins↗