Marleen Keijzer

Light distributions in a port wine stain model containing multiple cylindrical and curved blood vessels

Knowledge of the light distribution in skin tissue is important for the understanding, prediction, and improvement of the clinical results in laser treatment of port wine stains (PWS). The objective of this study is to improve modelling of PWS treated by laser using an improved and more realistic PWS model.

LIGHT DOSIMETRY FOR PHOTODYNAMIC THERAPY BY WHOLE BLADDER WALL IRRADIATION

Abstract In Photodynamic Therapy (PDT) there is a need for accurate quantitative light dosimetry. This has become particularly apparent in the treatment of superficial bladder cancer, either by focal or by whole bladder wall irradiation. We have studied this problem using a spherical model of the bladder, consisting of two concentric thin‐walled plastic spheres, 8 and 10 cm in diameter. The inner sphere was filled with water or with a light‐scattering medium. The space between the spheres was filled with an optically tissue equivalent liquid. An isotropic light source was placed at the center of the spheres. Light energy fluence rates (light “dose rates”) during PDT of the bladder simulated in this manner, were measured using a specially developed miniature light detector and were also calculated using a mathematical model. These data were confirmed by measurements in vivo (dog bladder). In the case of focal irradiation at a wavelength of 630 nm, the ratio (R) between the true light fluence rate at the bladder surface and the fluence rate due to the primary light beam is somewhat larger than 1, depending on the diameter of the primary beam. The maximum ratio is 2, for a beam diameter of several centimeters. In the case of whole bladder wall PDT, R is larger than 5. This is due to the strong scattering of (red) light by tissue and indicates that the intensity of the primary beam, which is usually reported, is not a good measure of the true fluence rate for whole bladder wall PDT. When the light source is moved away from the center of the spheres, the rate of change of the fluence rate at the bladder wall is more than a factor of 2 larger when the bladder cavity is filled with a light‐scattering suspension, as compared with water. The use of a light‐scattering medium may therefore not be advantageous to achieve a uniform light distribution across the bladder wall.

A novel approach to multi-criteria inverse planning for IMRT

Treatment plan optimization is a multi-criteria process. Optimizing solely on one objective or on a sum of a priori weighted objectives may result in inferior treatment plans. Manually adjusting weights or constraints in a trial and error procedure is time consuming. In this paper we introduce a novel multi-criteria optimization approach to automatically optimize treatment constraints (dose-volume and maximum-dose). The algorithm tries to meet these constraints as well as possible, but in the case of conflicts it relaxes lower priority constraints so that higher priority constraints can be met. Afterwards, all constraints are tightened, starting with the highest priority constraints. Applied constraint priority lists can be used as class solutions for patients with similar tumour types. The presented algorithm does iteratively apply an underlying algorithm for beam profile optimization, based on a quadratic objective function with voxel-dependent importance factors. These voxel-dependent importance factors are automatically adjusted to reduce dose-volume and maximum-dose constraint violations.

Modeling the effect of wavelength on the pulsed dye laser treatment of port wine stains

To determine the influence of wavelength on the depth of vascular injury in port wine stains following pulsed dye laser treatment, we calculated fluence rates at wavelengths varying from 415 to 590 nm in a two-layer Monte Carlo model representing the epidermis and the dermis. Calculations were made for four different volumetric fractions of blood in the dermis: 0%, 1%, 5%, and 10%. The depth of the selective vascular injury was determined to be the depth at which the rate of temperature rise at some point within the vessel just equals that at the epidermal-dermal junction. This was maximal between 577 and 590 nm with the maximum shifted toward 590 nm for a greater dermal blood content and for larger vessels. The effect of greater epidermal pigmentation was not only to reduce the depth of vascular injury but to shift slightly the wavelength of the maximum vascular injury to a shorter wavelength.

Fast, multiple optimizations of quadratic dose objective functions in IMRT

Inverse treatment planning for intensity-modulated radiotherapy may include time consuming, multiple minimizations of an objective function. In this paper, methods are presented to speed up the process of (repeated) minimization of the well-known quadratic dose objective function, extended with a smoothing term that ensures generation of clinically acceptable beam profiles. In between two subsequent optimizations, the voxel-dependent importance factors of the quadratic terms will generally be adjusted, based on an intermediate plan evaluation. The objective function has been written in matrix-vector format, facilitating the use of a recently published, fast quadratic minimization algorithm, instead of commonly applied gradient-based methods. This format also reduces the calculation time in between subsequent minimizations, related to adjustment of the voxel-dependent importance factors. Sparse matrices are used to limit the required amount of computer memory. For three patients, comparisons have been made with a gradient method. Mean speed improvements of up to a factor of 37 have been achieved.

Integrating sphere effect in whole bladder wall photodynamic therapy. I. 532 nm versus 630 nm optical irradiation

The optical absorption, scattering and anisotropy coefficients of piglet bladder, with and without Photofrin, and of diseased human bladder were determined in vitro with a double integrating sphere set-up in the wavelength range 450-800 nm. Monte Carlo simulations were performed in a spherical geometry, representing the bladder, using the optical properties at 532 nm and 630 nm determined in vitro. The calculated fluence rates support the fluence rates that were measured at the bladder wall of a piglet during an in vivo whole bladder wall (WBW) irradiation at 532 nm and 630 nm. Fluence rates calculated and measured in vivo at 630 nm are in agreement with those measured previously in clinical photodynamic therapy (PDT) at 630 nm. WBW-PDT with red light (630 nm) will be technically more advantageous than with green light (532 nm) because of a stronger integrating sphere effect, which reduces the variations of the fluence rate at the bladder wall when the isotropic light source is moved away from the centre of the bladder. Since the optical properties show considerable variations from bladder to bladder, and since as a result the light fluence rate at the bladder wall can vary by a factor of 3 to 4 for the same non-scattered light fluence rate, we conclude that in situ light dosimetry during clinical WBW-PDT is a necessity.

Integrating sphere effect in whole-bladder wall photodynamic therapy: III. Fluence multiplication, optical penetration and light distribution with an eccentric source for human bladder optical properties

Whole-bladder-wall (WBW) photodynamic therapy (PDT) is performed using approximately 630 nm light emitted by an isotropic light source centered in the bladder cavity. The phenomenon of an increased fluence rate in this spherical geometry, due to light scattering, is denoted as the integrating sphere effect. The fluence rate and the optical penetration depth depend on a single tissue optical parameter, namely the reduced albedo. The optical properties of (diseased) human bladder tissue, i.e. absorption coefficient, scattering coefficient, anisotropy factor and refractive index, were determined in vitro in the wavelength range of 450-880 nm. The integrating sphere effect and optical penetration depth were calculated with diffusion theory and compared to Monte Carlo (MC) computer simulations using approximately 630 nm optical properties. With increasing albedo, the integrating sphere effect calculated with diffusion approximation is increasingly larger than that found with MC simulations. Calculated and simulated optical penetration depths are in reasonable agreement. The smaller the integrating sphere effect for a given tissue absorption, the larger the optical penetration depth into the bladder wall, as the effective attenuation coefficient decreases. Optical penetration depths up to approximately 7.5 mm (definition dependent) can be responsible for unintended tissue damage beyond the bladder tissue. MC simulations were also performed with an eccentric light source and the uniformity of the light distribution at the bladder wall was assessed. The simulations show that even for a small eccentricity, the extremes in deviation from the mean fluence rate are large. All these results indicate that WBW PDT should be performed with some kind of in situ light dosimetry.

A population-based model to describe geometrical uncertainties in radiotherapy: applied to prostate cases

Local motions and deformations of organs between treatment fractions introduce geometrical uncertainties into radiotherapy. These uncertainties are generally taken into account in the treatment planning by enlarging the radiation target by a margin around the clinical target volume. However, a practical method to fully include these uncertainties is still lacking. This paper proposes a model based on the principal component analysis to describe the patient-specific local probability distributions of voxel motions so that the average values and variances of the dose distribution can be calculated and fully used later in inverse treatment planning. As usually only a very limited number of data for new patients is available; in this paper the analysis is extended to use population data. A basic assumption (which is justified retrospectively in this paper) is that general movements and deformations of a specific organ are similar despite variations in the shapes of the organ over the population. A proof of principle of the method for deformations of the prostate and the seminal vesicles is presented.

Integrating sphere effect in whole-bladder-wall photodynamic therapy: II. The influence of urine at 458, 488, 514 and 630 nm optical irradiation

Whole-bladder-wall (WBW) photodynamic therapy (PDT) performed with 458 nm instead of 630 nm wavelength might be advantageous. On the basis of Monte Carlo (MC) computer simulations using in vitro bladder optical properties, these wavelengths show an equally strong integrating sphere effect, while haematoporphyrin derivatives can be excited equally efficiently and more easily with an Ar+ laser at 458 nm. To test this, fluence rates were measured at the walls of two piglet bladders during in vivo and in vitro WBW optical irradiations at 458, 488, 514 and 630 nm. In the in vitro experiment, a controlled amount of urine with known absorption coefficient at the irradiation wavelengths was introduced in the bladder cavity. The optical absorption and scattering coefficients and anisotropy factor of the tissue of both piglet bladders were determined in vitro with a double integrating sphere set-up. MC simulations, using the in vitro optical properties, agree only partly with the measured bladder wall fluence rates. In the in vitro experiment with saline in the bladder cavity, the fluence rate at the bladder wall is lowest for 514 nm irradiation and highest for 458 and 630 nm irradiation. In the in vivo experiment and the in vitro experiment with light absorbing urine in the bladder cavity, which mimics the clinical situation, irradiation at 458 nm wavelength resulted in the lowest fluence rate for a given optical power emitted. It cannot be completely ruled out that in an in vivo bladder the light absorption by haemoglobin further reduces the integrating sphere effect at wavelengths shorter than 630 nm. Thus, WBW PDT with red light (630 nm) is technically more advantageous than that with green light (514 nm) or blue light (488 and 458 nm) as this gives the strongest integrating sphere effect.

Optimization of multileaf collimator settings for radiotherapy treatment planning

Multileaf collimators have become available in many radiotherapy treatment centres. The cross section of a beam can be shaped to a projection of the target area by moving the leaves of the multileaf collimator into the beam. In this paper, a method is described to optimize the positions of the individual leaves automatically, once the beam directions and weights have been chosen. The individual positions of the leaves are optimized using the variable metric method. Changes in dose resulting from small leaf movements are computed efficiently using a special method. The optimization method was tested on a treatment plan for a phantom patient. It was found that the unnecessary edges of the beams were trimmed efficiently.