Characterising 18F-fluciclovine uptake in breast cancer through the use of dynamic PET/CT imaging.

BACKGROUND: 18F-fluciclovine is a synthetic amino acid positron emission tomography (PET) radiotracer that is approved for use in prostate cancer. In this clinical study, we characterised the kinetic model best describing the uptake of 18F-fluciclovine in breast cancer and assessed differences in tracer kinetics and static parameters for different breast cancer receptor subtypes and tumour grades. METHODS: Thirty-nine patients with pathologically proven breast cancer underwent 20-min dynamic PET/computed tomography imaging following the administration of 18F-fluciclovine. Uptake into primary breast tumours was evaluated using one- and two-tissue reversible compartmental kinetic models and static parameters. RESULTS: A reversible one-tissue compartment model was shown to best describe tracer uptake in breast cancer. No significant differences were seen in kinetic or static parameters for different tumour receptor subtypes or grades. Kinetic and static parameters showed a good correlation. CONCLUSIONS: 18F-fluciclovine has potential in the imaging of primary breast cancer, but kinetic analysis may not have additional value over static measures of tracer uptake. CLINICAL TRIAL REGISTRATION: NCT03036943.

A medical expert system approach using artificial neural networks for standardized treatment planning.

PURPOSE: Many radiotherapy treatment plans involve some level of standardization (e.g., in terms of beam ballistics, collimator settings, and wedge angles), which is determined primarily by tumor site and stage. If patient-to-patient variations in the size and shape of relevant anatomical structures for a given treatment site are adequately sampled, then it would seem possible to develop a general method for automatically mapping individual patient anatomy to a corresponding set of treatment variables. A medical expert system approach to standardized treatment planning was developed that should lead to improved planning efficiency and consistency. METHODS AND MATERIALS: The expert system was designed to specify treatment variables for new patients based upon a set of templates (a database of treatment plans for previous patients) and a similarity metric for determining the goodness of fit between the relevant anatomy of new patients and patients in the database. A set of artificial neural networks was used to optimize the treatment variables to the individual patient. A simplified example, a four-field box technique for prostate treatments based upon a single external contour, was used to test the viability of the approach. RESULTS: For a group of new prostate patients, treatment variables specified by the expert system were compared to treatment variables chosen by the dosimetrists. Performance criteria included dose uniformity within the target region and dose to surrounding critical organs. For this standardized prostate technique, a database consisting of approximately 75 patient records was required for the expert system performance to approach that of the dosimetrists. CONCLUSIONS: An expert system approach to standardized treatment planning has the potential of improving the overall efficiency of the planning process by reducing the number of iterations required to generate an optimized dose distribution, and to function most effectively, should be closely integrated with a dosimetric based treatment planning system.

Cortical target depletion and the developing lateral geniculate nucleus: implications for trophic dependence.

The dependence of the developing dorsal lateral geniculate nucleus (LGd) on visual cortex for survival has been well documented. Complete removal of visual cortex during early postnatal development results in degeneration of the LGd. To further explore the nature of this trophic relationship, we depleted variable proportions of the principal targets of geniculocortical axons, layer IV neurons, and also variable proportions of the supragranular neurons by intraperitoneal injections of different dosages of a mitotic inhibitor MAM (methylazoxymethanol acetate) into pregnant hamsters at the time when these neurons were being generated in the ventricular zone. We demonstrate that after more than 75% loss of layer IV there is no reduction in cell number in the LGd. HRP (horseradish peroxidase) injections into the LGd in adult animals reveal an essentially normal pattern of termination without evidence of rerouting of geniculocortical axons to other cortical areas, nor compensatory increase in arborization in layer VI and VIb (subplate). Geniculocortical axons terminate principally in the middle stratum of the depleted cortex above layer V, with obvious reduction in both the extent and density of arborization. After higher dosages of MAM treatment resulting in more severe cell loss in layers II-IV with the apparent loss of layer IV, the extent and density of geniculocortical arborization are further reduced. Reduction in size as well as total number of geniculate neurons become detectable. Above depletions of 75% of layer IV neurons, the number of surviving LGd neurons is linearly related to the total number of remaining layer II-IV neurons in the cortex. These findings are discussed in light of the possible trophic mechanisms that match cell populations in number during development.

Damaging effect of therapeutic radiation on programmable pacemakers.

Two series of present-day pacemakers were tested in vitro with pulsed x-ray radiation. The first series of 12 pacemakers consisted of 10 different types and models of demand pacemakers (VVI). The second series of 13 pacemakers had 9 different types and models of programmable pacemakers. Unlike the first series which showed only mild changes in frequency and pulse width, all but four of the programmable pacemakers presented sudden complete failure after different radiation doses. We conclude that direct pulse radiation at therapeutic levels of programmable pacemakers should be avoided.

The response of cells in culture to fractionated radiation: a theoretical approach.

A mathematical model has been constructed to simulate the response of cells in vitro to fractionated doses of radiation. The model is capable of describing most of the radiobiological functions that are commonly studied. Input data are measurable cell properties. The details of the model and methods of acquiring the input data are outlined and a comparison with experimental observations on two radiobiological functions, survival curves and recovery curves are discussed in some detail.