Biologically effective dose (BED) treatment planning for Gamma Knife Radiosurgery

Gamma Knife (GK) radiosurgery treats brain lesions through multiple targeted radiation exposures of varying duration and spatial distribution. Clinical radiosurgery treatment planning only considers the total amount of delivered radiation. A biologically effective dose (BED) model allows quantifying the damage induced in a tissue due to radiation exposure while accounting for cellular repair. With this thesis work, we explore the potential and feasibility of using the more complex BED formulation to generate biologically-aware treatment plans. To this end, we quantify the impact of changes in the temporal domain of treatment delivery (i.e. beam-off periods, order of delivery), which need to be considered at the treatment planning stage to avoid undesirable BED variations. The delivery sequence alone can incur variations in marginal BED by up to 14%. Consideration of treatment delivery timing and sequence creates a nonconvex nonlinear treatment planning problem that is too computationally expensive to solve in a time-sensitive clinical setting. We develop multiple optimisation techniques to identify the most suitable one for a clinical workflow. While a convex underestimator approach provides slightly improved solutions, it requires several orders of magnitude more computational resources than local optimisation approaches that reach similar performance in terms of plan quality. In consultation with our clinical collaborators, we devise a BED treatment planning workflow that further reduces the possible planning times by combining pre-computation of candidate solutions with interactive exploration and refinement of the final treatment plans. To evaluate this workflow, we develop a prototype treatment planning framework. We show that BED optimisation removes the time dependence and further increases plan quality. The results of the proof-of-concept workflow demonstrate the feasibility of a future clinical application of BED planning in GK radiosurgery

Toward semi-automatic biologically effective dose treatment plan optimisation for Gamma Knife radiosurgery

Objective. Dose-rate effects in Gamma Knife radiosurgery treatments can lead to varying biologically effective dose (BED) levels for the same physical dose. The non-convex BED model depends on the delivery sequence and creates a non-trivial treatment planning problem. We investigate the feasibility of employing inverse planning methods to generate treatment plans exhibiting desirable BED characteristics using the per iso-centre beam-on times and delivery sequence. Approach. We implement two dedicated optimisation algorithms. One approach relies on mixed-integer linear programming (MILP) using a purposely developed convex underestimator for the BED to mitigate local minima issues at the cost of computational complexity. The second approach (local optimisation) is faster and potentially usable in a clinical setting but more prone to local minima issues. It sequentially executes the beam-on time (quasi-Newton method) and sequence optimisation (local search algorithm). We investigate the trade-off between time to convergence and solution quality by evaluating the resulting treatment plans’ objective function values and clinical parameters. We also study the treatment time dependence of the initial and optimised plans using BED95 (BED delivered to 95% of the target volume) values. Main results. When optimising the beam-on times and delivery sequence, the local optimisation approach converges several orders of magnitude faster than the MILP approach (minutes versus hours-days) while typically reaching within 1.2% (0.02-2.08%) of the final objective function value. The quality parameters of the resulting treatment plans show no meaningful difference between the local and MILP optimisation approaches. The presented optimisation approaches remove the treatment time dependence observed in the original treatment plans, and the chosen objectives successfully promote more conformal treatments. Significance. We demonstrate the feasibility of using an inverse planning approach within a reasonable time frame to ensure BED-based objectives are achieved across varying treatment times and highlight the prospect of further improvements in treatment plan quality

Therapeutic concentrations of glucagon-like peptide-1 in cerebrospinal fluid following cell-based delivery into the cerebral ventricles of cats

<p>Abstract</p> <p>Background</p> <p>Neuropeptides may have considerable potential in the treatment of acute and chronic neurological diseases. Encapsulated genetically engineered cells have been suggested as a means for sustained local delivery of such peptides to the brain. In our experiments, we studied human mesenchymal stem cells which were transfected to produce glucagon-like peptide-1 (GLP-1).</p> <p>Methods</p> <p>Cells were packed in a water-permeable mesh bag containing 400 polymeric microcapsules, each containing 3000 cells. The mesh bags were either transplanted into the subdural space, into the brain parenchyma or into the cerebral ventricles of the cat brain. Mesh bags were explanted after two weeks, and cell viability, as well as GLP-1 concentration in the cerebrospinal fluid (CSF), was measured.</p> <p>Results</p> <p>Viability of cells did not significantly differ between the three implantation sites. However, CSF concentration of GLP-1 was significantly elevated only after ventricular transplantation with a maximum concentration of 73 pM (binding constant = 70 pM).</p> <p>Conclusions</p> <p>This study showed that ventricular cell-based delivery of soluble factors has the capability to achieve concentrations in the CSF which may become pharmacologically active. Despite the controversy about the pharmacokinetic limitations of ventricular drug delivery, there might be a niche in this for encapsulated cell biodelivery of soluble, highly biologically-effective neuropeptides of low molecular weight like GLP-1.</p

Comparison of the visually evoked response in drug-free chronic schizophrenic patients and normal controls

Thirteen cooperative male drug-free chronic schizophrenic patients, and 11 mentally normal male controls were studied. The VER was recorded from scalp leads O1, O2, Oz, C3 and C4 to combined ear reference (A1---A2). The stimulus was an unpatterned flash of single intensity. Compared to normal controls, there were no consistent differences in wave peak latencies or amplitudes for chronic schizophrenics in any brain area tested. When the chronic schizophrenic patients were separated on the basis of high and low tryptophan uptake, using the Frohman-Gottlieb criteria, the high uptake group exhibited normal VERs while in the occipital regions the low tryptophan uptake group exhibited prolonged latencies and an increased amplitude for wave V when compared to normals. From BPRS scores the high tryptophan subgroup indicated a greater degree of psychopathology than the low tryptophan subgroup. The results obtained do not support an indole hallucinogen hypothesis for process schizophrenia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23636/1/0000600.pd

Experimental evaluation of the effectiveness of water mist automated fire extinguishing systems for oil transportation

Experimental investigation of regularities of carryover of water mist droplets (radius of 50 - 500 [mu]m) by high temperature (500 - 1800 K) products of combustion of typical petroleum products (oil, gasoline, kerosene, etc.) was carried out. The panoramic optical methods and high-speed hardware and software systems were used. Speeds of droplets after mixing with oncoming high temperature gases were determined. Conditions of continuation of droplets movement through combustion products with preservation of initial trajectory in spite of intensive evaporation and braking were found. The predictive evaluation of effectiveness of water mist use for extinguishing of fires involving oil and typical petroleum products

Исследование влияния различных видов излучения на структуру ДНК с помощью программы Geant4

В работе было произведено исследование влияния различных видов излучения на структуру ДНК с помощью программы Geant4. В результате работы было проведено моделирование повреждений молекулы ДНК от альфа частиц, электронов и протонов с энергиями от 100 КэВ до 1 МэВ. Гамма излучение не вызвало воздействий. Наибольшее влияние оказали альфа частицы и протоны.A study was made of the effect of various types of radiation on the DNA structure using the Geant4 program. As a result of the work, damage modeling of the DNA molecule from alpha particles, electrons and protons with energies from 100 KeV to 1 MeV was carried out. Gamma radiation caused no effects. Alpha particles and protons had the greatest impact