SciFi detector and associated method for real-time determination of profile and output factor for small fields in stereotactic radiotherapy.

PURPOSE: For determining small-field profile and output factor during stereotactic radiotherapy quality assurance (QA) procedures, we propose a novel system based on the scintillating fiber (SciFi) detector with output image acquisition and processing to allow real-time monitoring of profile and output factor. MATERIALS AND METHODS: The employed detector is a SciFi detector made of tissue-equivalent scintillating plastic fibers arranged in 6-layer fiber ribbons with a fiber pitch of 275 µm in each layer. The scintillating signal at the detector output is acquired by a sCMOS (scientific complementary metal-oxide-semiconductor) camera and represents the projected field profile along the fibers axis. An iterative reconstruction method of the field from its projected profile based on a priori knowledge of some features of the radiation field defined by the stereotactic cones is suggested. The detector with implemented data processing has been tested in clinical conditions, for determining beam profiles and output factors, using cone collimators of different sizes from 4 to 15 mm diameter. The detector under test was placed at 1.4 cm depth and 98.6 cm source to surface distance (SSD) in a water-equivalent phantom and irradiated by a 6 MV photon beam. RESULTS: The reconstructed field profiles obtained from the detector are coherent with data from EBT3 radiochromic films, with differences within ±0.32 mm for both the FWHM and the penumbra region. For real-time determination of the field output factor, the measured data are also in good agreement with data independently determined by the French Institute for Radiological Protection and Nuclear Safety (IRSN) based on radiochromic films and thermoluminescent 1 × 1 mm2 micro-cubes dosimeters (TLD). The differences are within ±1.6% for all the tested cone sizes. CONCLUSIONS: We propose and have tested a SciFi plastic scintillating detector with an optimized signal processing method to characterize small fields defined by cone collimators. It allows the determination of key field parameters such as full width at half maximum (FWHM) and field output factors. The results are consistent with those independently measured using TLD and radiochromic films. As the SciFi detector does not require a correction factor, it is in line with the International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) TRS-483 recommendations, and can be suitable for online QA of small radiation fields used in photon beam radiotherapy, and is compatible with MRI-LINAC.

Design and testing of a phantom and instrumented gynecological applicator based on GaN dosimeter for use in high dose rate brachytherapy quality assurance.

PURPOSE: High dose rate brachytherapy (HDR-BT) is widely used to treat gynecologic, anal, prostate, head, neck, and breast cancers. These treatments are typically administered in large dose per fraction (>5 Gy) and with high-gradient-dose-distributions, with serious consequences in case of a treatment delivery error (e.g., on dwell position and dwell time). Thus, quality assurance (QA) or quality control (QC) should be systematically and independently implemented. This paper describes the design and testing of a phantom and an instrumented gynecological applicator for pretreatment QA and in vivo QC, respectively. METHODS: The authors have designed a HDR-BT phantom equipped with four GaN-based dosimeters. The authors have also instrumented a commercial multichannel HDR-BT gynecological applicator by rigid incorporation of four GaN-based dosimeters in four channels. Specific methods based on the four GaN dosimeter responses are proposed for accurate determination of dwell time and dwell position inside phantom or applicator. The phantom and the applicator have been tested for HDR-BT QA in routine over two different periods: 29 and 15 days, respectively. Measurements in dwell position and time are compared to the treatment plan. A modified position-time gamma index is used to monitor the quality of treatment delivery. RESULTS: The HDR-BT phantom and the instrumented applicator have been used to determine more than 900 dwell positions over the different testing periods. The errors between the planned and measured dwell positions are 0.11 ± 0.70 mm (1σ) and 0.01 ± 0.42 mm (1σ), with the phantom and the applicator, respectively. The dwell time errors for these positions do not exhibit significant bias, with a standard deviation of less than 100 ms for both systems. The modified position-time gamma index sets a threshold, determining whether the treatment run passes or fails. The error detectability of their systems has been evaluated through tests on intentionally introduced error protocols. With a detection threshold of 0.7 mm, the error detection rate on dwell position is 22% at 0.5 mm, 96% at 1 mm, and 100% at and beyond 1.5 mm. On dwell time with a dwell time threshold of 0.1 s, it is 90% at 0.2 s and 100% at and beyond 0.3 s. CONCLUSIONS: The proposed HDR-BT phantom and instrumented applicator have been tested and their main characteristics have been evaluated. These systems perform unsupervised measurements and analysis without prior treatment plan information. They allow independent verification of dwell position and time with accuracy of measurements comparable with other similar systems reported in the literature.

Preliminary testing of GaN-based dosimeters for electron beam radiotherapy.

The response of an implantable in vivo dosimetric system based on gallium nitride radioluminescence was investigated for electron beam radiotherapy using ELEKTA SLi and VARIAN Clinac 2100 CD Linear Accelerators. A bi-channel method has been implemented for fibre background rejection. The percentage depth dose (PDD) profiles were measured in polymethyl methacrylate for 6, 12 and 18 MeV electron beams. The PDD results were in excellent agreement with those measured with reference to ionisation chambers.

Fiber background rejection and crystal over-response compensation for GaN based in vivo dosimetry.

For dosimetric measurements using an implantable optical fiber probe with GaN (Gallium Nitride) scintillator as radioluminescence (RL) transducer, a bi-channel method is proposed to reject the background contribution of the irradiated fiber segment. It is based on spectral differences between the narrow-band light emission from GaN and the large-band background from the irradiated optical fiber. Experimental validation of this method using 6 MV photon beam has shown that the remaining background contribution after subtraction is below 1.2% for square field sizes ranging from 3 cm to 20 cm. Furthermore, a compensation method for the over-response of GaN is also proposed, since GaN is not tissue equivalent. The over-response factor of GaN exhibits a linear increase with square field aperture and depends on depth from phantom surface. This behaviour is modelled to allow compensation in specific conditions. The proposed method has been evaluated and has shown a maximum deviation of 3% for a 6 MV photon beam and 1% for an 18 MV photon beam at a depth beyond the build-up region.

Radiotherapy quality assurance by individualized in vivo dosimetry: state of the art.

The quality insurance in radiotherapy in the frame of highly complex technical process as Intensity modulated radiotherapy (IMRT) needs independent control of the delivered dose to the patient. Actually, up to now, most of the radiotherapy treatments rely only on computed dosimetry through a rather complicated series of linked simulation tool. This dosimetry approach requires also qualified treatment means based on cautious quality insurance procedures. However, erroneous parameters could be difficult to detect and systematical errors could happen leading to radiotherapy accidents. In this context, in vivo dosimetry has a critical role of final control of the delivered dose. As many beam incidences and ports are used for any photontherapy treatment, external control could be very tedious and time consuming. Therefore, innovations are needed for in vivo dosimetry to provide ergonomic and efficient tools for these controls. This paper presents a review of technologies and products that can be used for in vivo dosimetry. It proposes also a reflection on the concepts to develop future devices suitable for this purpose. The technical means with their physical principles are reviewed, the clinical experiences demonstrating the feasibility of new techniques are then summarized and finally, the early clinical use and its impact on clinical practice is review.

Myofibroblast development is characterized by specific cell-cell adherens junctions.

Myofibroblasts of wound granulation tissue, in contrast to dermal fibroblasts, join stress fibers at sites of cadherin-type intercellular adherens junctions (AJs). However, the function of myofibroblast AJs, their molecular composition, and the mechanisms of their formation are largely unknown. We demonstrate that fibroblasts change cadherin expression from N-cadherin in early wounds to OB-cadherin in contractile wounds, populated with alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts. A similar shift occurs during myofibroblast differentiation in culture and seems to be responsible for the homotypic segregation of alpha-SMA-positive and -negative fibroblasts in suspension. AJs of plated myofibroblasts are reinforced by alpha-SMA-mediated contractile activity, resulting in high mechanical resistance as demonstrated by subjecting cell pairs to hydrodynamic forces in a flow chamber. A peptide that inhibits alpha-SMA-mediated contractile force causes the reorganization of large stripe-like AJs to belt-like contacts as shown for enhanced green fluorescent protein-alpha-catenin-transfected cells and is associated with a reduced mechanical resistance. Anti-OB-cadherin but not anti-N-cadherin peptides reduce the contraction of myofibroblast-populated collagen gels, suggesting that AJs are instrumental for myofibroblast contractile activity.

Epinephrine sensitivity with respect to metabolic rate and other variables in women.

A test for determination of epinephrine sensitivity has been worked out using six healthy young women. Variables considered were metabolic rate, heart rate, respiratory frequency, blood pressure, blood glucose, plasma insulin, glycerol, free fatty acids, and lactate. After established basal conditions, epinephrine was infused at rates of 0.01, 0.03, and 0.1 microgram X kg fat-free mass-1 X min-1. Most variables responded to epinephrine in a dose-dependent manner. Physiological threshold plasma concentrations of epinephrine ranged from 95 to 250 pg/ml for different variables. Calculated maximal responses ranged from approximately -15% to +900% of basal values and infusion rates giving half-maximal responses from approximately 15 to 190 ng X kg fat-free mass-1 X min-1. On an average, metabolic rate increased by 8, 16, and 29%, respectively, at the three infusion rates, and the maximal metabolic response was calculated to be approximately 35%. The error in determining epinephrine-induced increments in metabolic rate was 7% of the response. As calculated from nonprotein RQ, carbohydrate oxidation increased and lipid oxidation decreased rapidly during the first 10 min of epinephrine infusion. Later, fat oxidation became more important. Results on epinephrine plasma metabolic clearance rate agreed with earlier results in the literature.

Adipose tissue labelling in man, using a structurally-labelled fatty acid as tracer.

Three healthy male subjects had their adipose tissue enriched with a structurally-labelled fatty acid, 13-methyltetradecanoic acid (13-MTD), occurring naturally only in trace amounts. Needle biopsies from femoral, gluteal and abdominal adipose tissue were obtained at several intervals during a 6-week 13-MTD ingestion period and also along an 11-week period following the cessation of the label intake. Fatty acid composition was analysed by gas-liquid chromatography. Using this method, it was possible to show that different adipose tissues had various responsiveness to labelling (with abdominal fat having the highest one) and hence had different turnover rates. Incorporation and particularly disappearance rates were slow, half-lifes for label incorporation ranged from 2 to 12 weeks and that for label mobilization ranged from 4 to 10 months, thus confirming few other published results. The unexpected observation that incorporation of the label did not cease at the end of the 13-MTD feeding period, but did continue for at least a fortnight, might indicate that existence of a buffer pool where fatty acids may be momentarily stored before their definite incorporation into adipose tissue, as suggested in few other studies.

Metabolic effects of a mixed and a high-carbohydrate low-fat diet in man, measured over 24 h in a respiration chamber.

1. The relation between dietary carbohydrate: lipid ratio and the fuel mixture oxidized during 24 h was investigated in eleven healthy volunteers (six females, and five males) in a respiration chamber. Values of the fuel mixture oxidized were estimated by continuous indirect calorimetry and urinary nitrogen measurements. 2. The subjects, were first given a mixed diet for 7 d and spent the last 24 h of the 7 d period in a respiration chamber for continuous gas-exchange measurement. The fuels oxidized during 2.5 h or moderate exercise were also measured in the respiration chamber. After an interval of 2 weeks from the end of the mixed-diet period, the same subjects were given an isoenergetic high-carbohydrate low-fat diet for 7 d, and the same experimental regimen was repeated. 3. Dietary composition markedly influenced the fuel mixture oxidized during 24 h and this effect was still present 12 h after the last meal in the postabsorptive state. However, the diets had no influence on the substrates oxidized above resting levels during exercise. With both diets, the 24 h energy balance was slightly negative and the energy deficit was covered by lipid oxidation. 4. With the high-carbohydrate low-fat diet, the energy expenditure during sleep was found to be higher than that with the mixed diet. 5. It is concluded that: (a) the composition of the diet did not influence the fuel mixture utilized for moderate exercise, (b) the energy deficit calculated for a 24 h period was compensated by lipid oxidation irrespective of the carbohydrate content of the diet, (c) energy expenditure during sleep was found to be higher with the high-carbohydrate low-fat diet than with the mixed diet.

The use of 13-methyltetradecanoic acid as an indicator of adipose tissue turnover.

We show in this paper that 13-methyltetradecanoic acid (13-MTD) can be used as a structually labeled marker for investigating the mobility of fatty acyl chains in adipose tissue in the rat. The presence of an omega-1 methyl group allows easy quantitation by gas liquid chromatography (GLC) and permits an assessment to be made of any oxidation and chain elongation reactions with reincorporation of the label into the adipose tissue, since the iso-acyl chain is well resolved from odd or even-numbered homologous fatty acids with straight chains. The kinetics of uptake and loss of the structural label were different for adipose tissue taken from the various sites which were sampled, namely post abdominal, mesenteric, perirenal, pericardiac and subcutaneous adipose tissue as well as the epidydimal fat pads. We also report preliminary results in man which confirm that the method is applicable to human clinical studies and that 13-MTD kinetics differ for adipose tissue taken from the 3 different subcutaneous sites--waist, arm and thigh.

Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals.

A series of four trials was carried out to investigate the effects of caffeine and coffee on the metabolic rate and substrate utilization in normal weight and obese individuals. In the first trial 8 mg/kg caffeine was compared with a placebo in normal weight subjects. Metabolic rate increased significantly during the 3 hr after caffeine ingestion. While plasma glucose, insulin, and carbohydrate oxidation did not change significantly, plasma free fatty acid levels rose from 432 +/- 31 to 848 +/- 135 muEq/liter and were accompanied by significant increases in fat oxidation during the last hour of the test. In the second and third trials the effects of coffee providing 4 mg/kg caffeine were studied in control and obese subjects. Metabolic rate increased significantly in both groups; however, significant increases in fat oxidation were only observed in the control group. Plasma free fatty acids did not change in the obese. In the fourth trial, coffee was taken with a 3080 kJ meal. The thermic effect of the meal was significantly greater after coffee than after decaffeinated coffee and again fat oxidation was significantly greater after coffee. In conclusion caffeine/coffee stimulates the metabolic rate in both control and obese individuals; however, this is accompanied by greater oxidation of fat in normal weight subjects.

A new method for measuring the body density of obese adults.

1. A new apparatus is described with which it is possible to measure the volume (and hence density) of obese patients without requiring them to immerse totally in water. Replicate measurements of subjects with 6, 23 and 38 kg body fat had a standard deviation not greater than 0.3 kg fat. 2. In nineteen obese women body fat was measured by density, total body water, and total body potassium at the beginning, and again at the end, of a period of 3--4 weeks on a reducing diet, during which they lost 5.43 (SD 1.83) kg in weight. The composition of weight loss was also estimated both by energy balance and nitrogen balance during the interval between the two measurements of body composition. 3. The estimates of fat content of the ninetten women at the start of the balance period were 45.63 (SD 14.50) kg by density, 48.07 (SD 13.88) kg by K and 47.09 (SD 13.85) kg by water. The correlation coefficient between the density and K estimate was 0.949, and for the density and water estimate it was 0.971. 4. It is concluded that measurement of density by the new method provides a convenient method for estimating body fatness, and change in fat content, which compares favourably with estimates based on total body water or total body K. However, these methods cannot be used to provide an accurate estimate of the composition of a small weight loss in an individual since deviations up to 4 kg fat occur between fat loss based on change in density and those based on the more reliable (but more tedious) energy balance method.

Site differences in the fatty acid composition of subcutaneous adipose tissue of obese women.

1. Adipose tissue samples were obtained by needle biopsy from three subcutaneous sites (thigh, abdomen and upper arm) in twenty-two obese women. The fatty acid composition was determined using gas-liquid chromatography and the results presented relate to eleven component fatty acids. 2. The fatty acid composition of adipose tissue obtained from the arm and abdomen was remarkably similar, with the exception of the levels of lauric acid. 3. The analyses showed that the majority of the saturated fatty acids were present in smaller proportions whilst the majority of unsaturated fatty acids were present in larger proportions in the thigh than in the two other sites. Highly significant inter-site differences were demonstrated for six of the major fatty acids and also for both the total amounts of saturated and unsaturated fatty acids and their ratios. 4. No marked differences in the fatty acid composition of adipose tissue from obese subjects were revealed during this study when compared with previously reported results obtained from 'normal-weight' subjects.

Role of nutrition in the development of osteomalacia in the elderly.

A dietary survey has been carried out of elderly people with osteomalacia. The commonest type of osteomalacia was that associated with partial gastrectomy. Although a dietary deficiency of vitamin D has been suggested as a cause of the osteomalacia the intake of this substance was not significantly different from that in controls to explain the development of the disease. It was found, however, that patients with osteomalacia went outside much less than controls and given the contribution of sunlight to meeting vitamin D requirements it is suggested that further consideration should be given to this factor in the aetiology of post-gastrectomy osteomalacia.