Knowledge-based isocenter selection in radiosurgery planning.

PURPOSE: We present a new method for knowledge-based isocenter selection for treatment planning in radiosurgery. Our objective is to develop a prediction model that can learn from past manually designed treatment plans. We leverage recent advances in deep learning to predict isocenter locations in treatment plans in order to provide a decision support tool. METHODS: The proposed method adapts a geometric approach using orthogonal moment expansions as a feature vector for describing the shape of the tumor. Our approach accounts primarily for tumor shape and OAR proximity, the two factors that are known to greatly affect the isocenter placement. We solve the prediction problem by training a residual neural network with skip connections on the formed shape descriptors. Our network was trained on 533 patient cases and was validated on a set of out-of-sample cases. RESULTS: Our method generates heatmap predictions for isocenter locations that are in most cases comparable to the experienced human planners, which shows that the method can be used in treatment planning to guide the users for determining the isocenters. CONCLUSIONS: Our numerical experiments indicate a positive predictive value on an independent validation set when compared against a test dataset that was not seen by the model during training.

Monte Carlo kilovoltage X-ray tube simulation: A statistical analysis and compact simulation method.

INTRODUCTION: Monte Carlo (MC) simulations are a powerful tool for improving image quality in X-ray based imaging modalities. An accurate X-ray source model is essential to MC modeling for CBCT but can be difficult to implement on a GPU while maintaining efficiency and memory limitations. A statistical analysis of the photon distribution from a MC X-ray tube simulation is conducted in hopes of building a compact source model. MATERIALS & METHODS: MC simulations of an X-ray tube were carried out using BEAMnrc. The resulting photons were sorted into four categories: primary, scatter, off-focal radiation (OFR), and both (scatter and OFR). A statistical analysis of the photon components (energy, position, direction) was completed. A novel method for a compact (memory efficient) representation of the PHSP data was implemented and tested using different statistical based linear transformations (PCA, ZCA, ICA), as well as a geometrical transformation. RESULTS: The statistical analysis showed all photon groupings had strong correlations between position and direction, with the largest correlation in the primary data. The novel method was successful in compactly representing the primary (error < 2%) and scatter (error < 6%) photon groupings by reducing the component correlations. DISCUSSION & CONCLUSION: Statistical linear transforms provide a method of reducing the memory required to accurately simulate an X-ray source in a GPU MC system. If all photon types are required, the proposed method reduces the memory requirements by 3.8 times. When only primary and scatter data is needed, the memory requirement is reduced from gigabytes to kilobytes.

A linear programming approach to inverse planning in Gamma Knife radiosurgery.

PURPOSE: Leksell Gamma Knife® is a stereotactic radiosurgery system that allows fine-grained control of the delivered dose distribution. We describe a new inverse planning approach that both resolves shortcomings of earlier approaches and unlocks new capabilities. METHODS: We fix the isocenter positions and perform sector-duration optimization using linear programming, and study the effect of beam-on time penalization on the trade-off between beam-on time and plan quality. We also describe two techniques that reduce the problem size and thus further reduce the solution time: dualization and representative subsampling. RESULTS: The beam-on time penalization reduces the beam-on time by a factor 2-3 compared with the naïve alternative. Dualization and representative subsampling each leads to optimization time-savings by a factor 5-20. Overall, we find in a comparison with 75 clinical plans that we can always find plans with similar coverage and better selectivity and beam-on time. In 44 of these, we can even find a plan that also has better gradient index. On a standard GammaPlan workstation, the optimization times ranged from 2.3 to 26 s with a median time of 5.7 s. CONCLUSION: We present a combination of techniques that enables sector-duration optimization in a clinically feasible time frame.

Simultaneous optimization of isocenter locations and sector duration in radiosurgery.

Stereotactic radiosurgery is an effective technique to treat brain tumors for which several inverse planning methods may be appropriate. We propose an integer programming model to simultaneous sector duration and isocenter optimization (SDIO) problem for Leksell Gamma Knife® IconTM (Elekta, Stockholm, Sweden) to tractably incorporate treatment time. We devise a Benders decomposition scheme to solve the SDIO problem to optimality. The performances of our approaches are assessed using anonymized data from eight previously treated cases, and obtained treatment plans are compared against each other and against the clinical plans. The plans generated by our SDIO model all meet or exceed clinical guidelines while demonstrating high conformity.

Modeling and comparison of alternative approaches for sector duration optimization in a dedicated radiosurgery system.

Stereotactic radiosurgery (SRS) is an effective technique to treat brain metastasis for which several inverse planning methods may be appropriate. We compare three different optimization models for segment duration optimization in SRS using Leksell Gamma Knife® IconTM (Elekta, Stockholm, Sweden). We investigate (1) a linear programming approach, (2) a piecewise quadratic penalty approach, and (3) an unconstrained convex moment-based penalty approach. We examine the performances of these approaches using anonymized data from 14 previously treated cases. In addition, we investigate the important modeling question of selecting weights for the objective functions where we use a simulated annealing algorithm to determine these weights for each model. The inverse plans obtained via optimization models are compared against each other and against the clinical plans. The three inverse planning models can all yield optimal treatment plans in a reasonable amount of time and the treatment plans obtained by these models meet or exceed clinical guidelines while displaying high conformity.

Plasma lidocaine levels and risks after liposuction with tumescent anaesthesia.

BACKGROUND: It is common today to use tumescent anaesthesia with large doses of lidocaine for liposuction. The purpose of the present study was to evaluate lidocaine plasma levels and objective and subjective symptoms during 20 h after tumescent anaesthesia with approximately 35 mg per kg bodyweight of lidocaine for abdominal liposuction. METHODS: Three litres of buffered solution of 0.08% lidocaine with epinephrine was infiltrated subcutaneously over the abdomen in eight female patients during monitored intravenous (i.v.) light sedation. Plasma levels of lidocaine and signs of subjective and objective symptoms were recorded every 3 h for 20 h after liposuction. RESULTS: Lidocaine 33.2 +/- 1.8 mg/kg was given at a rate of 116 +/- 11 ml/min. Peak plasma levels (2.3 +/- 0.63 microg/ml) of lidocaine occurred after 5-17 h. No correlation was found between peak levels and dose per kg bodyweight or total amount of lidocaine infiltrated. One patient experienced tinnitus after 14 h when a plasma level of 3.3 microg/ml was recorded. CONCLUSION: Doses of lidocaine up to 35 mg/kg were sufficient for abdominal liposuction using the tumescent technique and gave no fluid overload or toxic symptoms in eight patients, but with this dose there is still a risk of subjective symptoms in association with the peak level of lidocaine that may appear after discharge.

Effects of hyperbaric oxygen treatment in post-ischemic muscle. A quantitative morphological study.

In the post-ischemic muscle, hyperbaric oxygen (HBO) treatments have been shown to reduce post-ischemic edema and enhance aerobic metabolism. In the present paper histological, histochemical and ultrastructural methods were used to study the influences of HBO treatment on the morphology of post-ischemic skeletal muscle. The changes were also quantified using morphometry. The circulation of the rat hindlimb was interrupted for 3 hours and muscle biopsies were taken 5 and 12 hours post-ischemia. Light microscopy showed signs of ischemic changes in the muscle. Morphometrically, the area with activity of the muscle enzyme phosphorylase was greatly reduced post-ischemia. HBO treatment at 2.5 atmospheres of absolute pressure (ATA) for 45 min significantly increased muscle cross sectional area with a positive phosphorylase reaction 5 hours post-ischemia. Three HBO treatments were necessary to maintain this effect, 12 hours post-ischemia. Ultrastructurally, the ischemic changes seen using light microscopy were confirmed. Morphometrically, there was a significant increase of mitochondrial size in the ischemic muscle compared with the control uninjured muscle but HBO did not markedly reduce these ultrastructural changes. It was concluded that the reduction of phosphorylase activity, a sensitive marker for muscle cell damage, is to a great extent prevented by HBO treatment in the post-ischemic phase.

Influence of injury and nutrition on muscle water and electrolytes: effect of severe injury, burns and sepsis.

The changes in water and electrolyte metabolism associated with severe injury and sepsis are well recognized but changes in tissue content have seldom been available. This report combines the experience obtained from muscle biopsies of such patients performed in two centers; one located in Sweden and one in the U.S. Normal values for muscle water and electrolytes in each center are in close agreement. Needle biopsies of muscle were performed in 45 Swedish patients and 17 U.S. patients at intervals after injury or infection from the second to the thirtieth day. The patients' nutrition varied from brief periods of hypocaloric intake to prolonged high calorie parenteral nutrition with and without amino acids, as well as with and without fat. Prominent changes appeared during the first week and persisted up to 30 days regardless of the associated nutritional intake. These changes included an increased total muscle water, extracellular water, sodium and chloride and a decrease in muscle potassium and magnesium. This study demonstrates a simultaneous expansion of extracellular volume and a loss of intracellular components. This is in contrast to the experiences reported with less severe injury such as elective operation, where a more modest expansion of extracellular volume is seen and which is not associated with any loss of potassium or magnesium. The magnitude and persistence of these changes in muscle tissue deserve further study, both as to mechanism and implications for therapy.

Amino acid metabolism during the anabolic phase of severely burned patients: with special reference to sulphur amino acids.

Owing to the high content of cyst(e)ine and sulphated mucopolysaccharides in skin tissues, an increased demand for sulphur amino acids could be expected during the anabolic phase in severely burned patients. As a marker for sulphur amino acid deficiency, leucocyte glutathione, methionine and taurine concentrations and urinary excretion of sulphur amino acids and inorganic sulphate were followed in five severely burned patients during a 5-month period (1-6 months post injury). Reduced leucocyte concentrations of glutathione, methionine and taurine, and decreased urinary excretion of inorganic sulphate, methionine, cyst(e)ine and taurine were observed, and were most pronounced 2 or 3 months after injury. Simultaneously a minor decrease in urinary output and leucocyte concentration of branched-chain amino acids and serine were also found, whereas normal levels of glycine, threonine, and glutamine were registered. The episode of limited availability of sulphur amino acids coincides with the period of most intensive collagen and keratin resynthesis of burned skin tissue.

Metabolic effects of hyperbaric oxygen in postischemic muscle.

In traumatic injuries to the extremities, with a circulatory insufficiency, the resultant ischemia leads to decreasing levels of the energy-rich compounds adenosine triphosphate (ATP) and phosphocreatine (PCr) and increasing levels of lactate in muscle. A tourniquet model for temporary ischemia was used to determine if hyperbaric oxygen treatment could enhance the cellular metabolic restitution when the circulation was restored. The circulation of the rat hindlimb was interrupted for 1.5 and 3 hours. After 1.5 hours of ischemia, the levels of adenosine triphosphate, phosphocreatine, and lactate were restored to normal in muscle biopsies taken 5 hours after the ischemia. After 3 hours of ischemia, there were marked reductions of adenosine triphosphate and phosphocreatine and elevated lactate values in the postischemic muscle, indicating severe ischemic damage. Hyperbaric oxygen treatment at 2.5 atm for 45 minutes reduced these changes significantly. A certain number of hyperbaric oxygen treatments were necessary to maintain this effect. It is concluded that repeated hyperbaric oxygen treatments in the postischemic phase stimulate aerobic metabolism.

Serum phosphate and 2,3-diphosphoglycerate in severely burned patients after phosphate supplementation.

Serum phosphate (S-P) and 2,3-diphosphoglycerate (2,3-DPG) were monitored for 10 days after severe burn trauma in 16 patients treated with total parenteral nutrition, including supplementation with 25-75 mmol phosphate daily. Phosphate metabolism was previously shown to be disturbed in patients with severe burns, and hypophosphatemia has been reported to disturb oxygen transport by reducing synthesis of 2,3-DPG in the red cells. In this study, S-P was decreased in the first post-trauma week because of a negative phosphate balance the first 4 post-trauma days, but 2,3-DPG remained at normal concentrations. These findings indicate that post-traumatic disturbance in red-cell phosphate metabolism may be prevented by administration of phosphate and that such supplementation is important in the metabolic management of severely injured patients.

Reduction of postischemic edema with hyperbaric oxygen.

In recent years, reports have shown positive effects of hyperbaric oxygen (HBO) treatment in posttraumatic circulatory insufficiency of the extremities. A tourniquet model for temporary ischemia was used to examine such treatment in rats. The circulation of the rat hindlimb was interrupted for 3 hours, while the contralateral uninjured leg served as control. There was a significant (p less than 0.001) postischemic edema in the tourniquet leg up to 48 hours after restoration of circulation. One group of animals received treatment with hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for 45 minutes after release of the tourniquet. This significantly reduced (p less than 0.001) the postischemic edema, and the reduction persisted for 40 hours after the last treatment. It is concluded that hyperbaric oxygen reduces postischemic edema. Hyperbaric oxygen may therefore be useful as an adjuvant in the treatment of acute ischemic conditions when surgical repair alone fails or is not sufficient to reverse the ischemic process.

Effects of hyperbaric oxygen on oedema formation after a scald burn.

Hyperbaric oxygen (HBO) has been advocated as an adjuvant in the therapy of thermal burns. One of the positive effects was reported to be a decrease in fluid requirements. The effect of HBO on oedema formation was evaluated in the burned area and in distant areas. Fifty-four mice were used in a standardized scald burn model, burning their left ear. Biopsies were taken from the left and right ear and from the quadriceps muscle 2, 6 and 24 hours after burn. Half of the group was treated with HBO immediately after burn. In the burned HBO treated group the oedema of the burned ear was not significantly different from that of burned untreated mice. With HBO treatment the water content in the contralateral ear was significantly (P less than 0.01) lower and in these animals the water content of the contralateral uninjured ear was not significantly different from that of uninjured untreated animals. In the burned HBO treated animals there was a significantly (P less than 0.05) lower water content of the quadriceps muscle 2 and 24 hours after burn compared to the burned untreated animals. This experimental study indicates a significant reduction of the general post-burn oedema with a HBO treatment.

Vitamin B12 deficiency after partial gastrectomy.

In a prospective study vitamin B12 concentration was assayed in 22 patients before and 6.4 years after partial gastrectomy. S-B12 had decreased from 496 to 274 pg/ml, p less than 0.001. Four patients had pathological values and two were already on B12 substitution because of deficiency. No difference in B12 concentration was found between patients with gastric or duodenal ulcers or between Billroth I and II operations. Other hematological tests were normal, and the nutritional status of the patients was satisfactory. It is concluded that regular postoperative controls of S-B12 or prophylactic B12 therapy is indicated in these patients.

Changes in calcium and phosphate and their regulating hormones in patients with severe burn injuries.

Changes in the calcium- and phosphate homeostasis and its regulating hormones calcitonin (CT) and parathyroid hormone (PTH) are of great importance for several pathophysiological reactions after trauma. In this study calcium, phosphate, CT, PTH and nor-adrenaline, were followed during 14 days after trauma in 20 patients with severe burn injuries. The results showed significantly reduced serum phosphate (S-P) during the first week after trauma, and low ionized calcium fraction (CaF) during the 14 post-traumatic days that were studied. Urinary calcium output was low, about 4.5 mmol/day and urinary phosphate output was as high as 30 mmol/day, despite the low S-P. Plasma nor-adrenaline was elevated with maximum concentrations 6 days after trauma. CT was very high with levels around 1 000 pmol/l after one week. PTH remained within the reference interval, although a statistically significant increase was observed four days after the trauma. The results suggest that the observed changes in calcium- and phosphate homeostasis were related to the humoral response to trauma.

Urinary excretion of sulfur amino acids and sulfur metabolites in burned patients receiving parenteral nutrition.

The urinary excretion of sulfur-containing compounds was studied in 11 burned patients during the first 10 days after injury. They were all given carbohydrate and fat by parenteral nutrition. Two patients also received large amounts of amino acids including methionine, whereas five patients were given amino acids including moderate amounts of methionine and cysteine. A sustained high excretion of mercaptolactate occurred in most patients. The excretion was not influenced by the type of parenteral nutrition, but related to the area of burned skin. A normal excretion of methionine, cyst(e)ine, inorganic sulfate, taurine, mercaptoacetate, thiosulfate, and thiocyanate was found at the end of the observation period in patients without amino acid therapy. Increased amounts of inorganic sulfate and methionine were excreted in patients receiving high doses of methionine, whereas an increased cyst(e)ine and taurine excretion was the most prominent finding in patients receiving moderate amounts of methionine and cysteine. These results indicate that burned patients have an unimpaired ability to metabolize sulfur amino acids. Patients not receiving amino acids or receiving moderate amounts of cysteine and methionine showed a negative sulfur balance, whereas patients given high doses of methionine maintained sulfur balance at near-zero levels. However, since signs of hepatic dysfunction appeared in the latter group, parenteral nutrition with amino acid mixtures containing high amounts of methionine is not recommended during the catabolic phase for burned patients.

Traumatically induced hypophosphataemia in anaesthetized pigs.

Clinical studies in severely injured patients have regularly shown hypophosphataemia probably directly related to the humoral response to trauma. In this study 72 anaesthetized pigs were exposed to a standardized missile trauma to find out whether the same type of change could be induced in an experimental animal as far as possible in the absence of other factors known to cause hypophosphataemia. The serum phosphate, calcium, and albumin concentrations and the fractional excretion of phosphate were recorded for 72 hours after inflicting the injury. The fall in serum phosphate after trauma follows a biphasic pattern, with a rapid drop immediately after the injury, a brief increase, and then a gradual slow decrease with a minimum at the end of the experimental period. This decrease was not caused by glucose infusion or phosphaturia due to haemodilution and increase in extracellular volume. The results support the hypothesis that hypophosphataemia in the posttraumatic period is caused by the humoral response to trauma. A new experimental model has been developed for the study of posttraumatic metabolic events.

Warm dry air treatment of 345 patients with burns exceeding 20 per cent of the body surface.

Two groups of patients with burns covering more than 20% of the body surface treated in a warm dry environment in two Burn Units in Sweden have been compared. The methods of treatment of the 345 patients were almost identical, using plasma and crystalloid solutions during the period of early intense therapy, use of frequent bathing and early debridement of the necrotic burned tissue and application of homo- or heterograft skin prior to the transplantation of autograft skin. The percentage mortalities in the two groups of patients (15.7% and 20.2%) were not significantly different, neither were the causes of the burn or the cause of death. Combination of the results and probit analysis did however show that treatment in a warm dry environment was associated with a lower rate of mortality in patients with very extensive burns than found in other studies not using these environmental conditions in Sweden prior to 1968 (by the same authors) in the United Kingdom and in the United States of America.

Hypophosphatemia in severe burns. A prospective study.

In 33 severely burned patients, who were followed for two weeks after injury, a transient hypophosphatemia was registered with the decrease in serum phosphate occurring on the second to tenth day after injury. When a previous retrospective study was combined with the present one, there were 50 patients in all. Seven patients died and, of these, five showed very low values of serum phosphate (S-P) at the time of their death. Simultaneous reduction of urinary phosphate excretion indicates that the depletion of phosphate is mainly prerenal. However, studies of fractional excretion of phosphate demonstrates that renal losses of phosphate might contribute to the hypophosphatemia. A remarkable finding was a general, marked rise in serum calcitonin (S-h-CT). The relationship between the rise in S-h-CT, the increased catecholamine secretion and the hypophosphatemia remains to be further clarified.