Astrid van der Horst

Cardiac and lung complication probabilities after breast cancer irradiation

PURPOSE To assess for locoregional irradiation of breast cancer patients, the dependence of cardiac (cardiac mortality) and lung (radiation pneumonitis) complications on treatment technique and individual patient anatomy. MATERIALS AND METHODS Three-dimensional treatment planning was performed for 30 patients with left-sided breast cancer and various breast sizes. Two locoregional techniques (Techniques A and B) and a tangential field technique, including only the breast in the target volume, were planned and evaluated for each patient. In both locoregional techniques tangential photon fields were used to irradiate the breast. The internal mammary (IM)-medial supraclavicular (MS) lymph nodes were treated with an anterior mixed electron/photon field (Technique A) or with an obliquely incident mixed electron/photon IM field and an anterior electron/photon MS field (Technique B). The optimal IM and MS electron field dimensions and energies were chosen on the basis of the IM-MS lymph node target volume as delineated on CT-slices. The position of the tangential fields was adapted to match the IM-MS fields. Dose-volume histograms (DVHs) and normal tissue complication probabilities (NTCPs) for the heart and lung were compared for the three techniques. In the beams eye view of the medial tangential fields the maximum distance of the heart contour to the posterior field border was measured; this value was scored as the Maximum Heart Distance. RESULTS The lymph node target volume receiving more than 85% of the prescribed dose was on average 99% for both locoregional irradiation techniques. The breast PTV receiving more than 95% of the prescribed dose was generally smaller using Technique A (mean: 90%, range: 69-99%) than using Technique B (mean: 98%, range: 82-100%) or for the tangential field technique (mean: 98%, range: 91-100%). NTCP values for excess cardiac mortality due to acute myocardial ischemia varied considerably between patients, with minimum and maximum values of 0.1 and 7.5% (Technique A), 0.1 and 5.8% (Technique B) and 0.0 and 6.1% (tangential tech.). The NTCP values were on average significantly higher (P<0.001) by 1.7% (Technique A) and 1.0% (Technique B) when locoregional breast irradiation was given, compared with irradiation of the left breast only. The NTCP values for the tangential field technique could be estimated using the Maximum Heart Distance. NTCP values for radiation pneumonitis were very low for all techniques; between 0.0 and 1.0%. CONCLUSIONS Technique B results in a good coverage of the breast and locoregional lymph nodes, while Technique A sometimes results in an underdosage of part of the target volume. Both techniques result in a higher probability of heart complications compared with tangential irradiation of the breast only. Irradiation toxicity for the lung is low in all techniques. The Maximum Heart Distance is a simple and useful parameter to estimate the NTCP values for cardiac mortality for tangential breast irradiation.

Optical tweezers and confocal microscopy for simultaneous three-dimensional manipulation and imaging in concentrated colloidal dispersions

A setup is described for simultaneous three-dimensional manipulation and imaging inside a concentrated colloidal dispersion using (time-shared) optical tweezers and confocal microscopy. The use of two microscope objectives, one above and one below the sample, enables imaging to be completely decoupled from trapping. The instrument can be used in different trapping (inverted, upright, and counterpropagating) and imaging modes. Optical tweezers arrays, dynamically changeable and capable of trapping several hundreds of micrometer-sized particles, were created using acousto-optic deflectors. Several schemes are demonstrated to trap three-dimensional colloidal structures with optical tweezers. One combined a Pockels cell and polarizing beam splitters to create two trapping planes at different depths in the sample, in which the optical traps could be manipulated independently. Optical tweezers were used to manipulate collections of particles inside concentrated colloidal dispersions, allowing control over collo...

Calibration of dynamic holographic optical tweezers for force measurements on biomaterials

Holographic optical tweezers (HOTs) enable the manipulation of multiple traps independently in three dimensions in real time. Application of this technique to force measurements requires calibration of trap stiffness and its position dependence. Here, we determine the trap stiffness of HOTs as they are steered in two dimensions. To do this, we trap a single particle in a multiple-trap configuration and analyze the power spectrum of the laser deflection on a position-sensitive photodiode. With this method, the relative trap strengths can be determined independent of exact particle size, and high stiffnesses can be probed because of the high bandwidth of the photodiode. We find a trap stiffness for each of three HOT traps of kappa approximately 26 pN/microm per 100 mW of laser power. Importantly, we find that this stiffness remains constant within +/- 4% over 20 microm displacements of a trap. We also investigate the minimum step size achievable when steering a trap with HOTs, and find that traps can be stepped and detected within approximately 2 nm in our instrument, although there is an underlying position modulation of the traps of comparable scale that arises from SLM addressing. The independence of trap stiffness on steering angle over wide ranges and the nanometer positioning accuracy of HOTs demonstrate the applicability of this technique to quantitative study of force response of extended biomaterials such as cells or elastomeric protein networks.

Interfractional position variation of pancreatic tumors quantified using intratumoral fiducial markers and daily cone beam computed tomography

PURPOSE The aim of this study was to quantify interfractional pancreatic position variation using fiducial markers visible on daily cone beam computed tomography (CBCT) scans. In addition, we analyzed possible migration of the markers to investigate their suitability for tumor localization. METHODS AND MATERIALS For 13 pancreatic cancer patients with implanted Visicoil markers, CBCT scans were obtained before 17 to 25 fractions (300 CBCTs in total). Image registration with the reference CT was used to determine the displacement of the 2 to 3 markers relative to bony anatomy and to each other. We analyzed the distance between marker pairs as a function of time to identify marker registration error (SD of linear fit residuals) and possible marker migration. For each patient, we determined the mean displacement of markers relative to the reference CT (systematic position error) and the spread in displacements (random position error). From this, we calculated the group systematic error, Σ, and group random error, σ. RESULTS Marker pair distances showed slight trends with time (range, -0.14 to 0.14 mm/day), possibly due to tissue deformation, but no shifts that would indicate marker migration. The mean SD of the fit residuals was 0.8 mm. We found large interfractional position variations, with for 116 of 300 (39%) fractions a 3-dimensional vector displacement of >10 mm. The spread in displacement varied significantly (P<.01) between patients, from a vector range of 9.1 mm to one of 24.6 mm. For the patient group, Σ was 3.8, 6.6, and 3.5 mm; and σ was 3.6, 4.7 and 2.5 mm, in left-right, superior-inferior, and anterior-posterior directions, respectively. CONCLUSIONS We found large systematic displacements of the fiducial markers relative to bony anatomy, in addition to wide distributions of displacement. These results for interfractional position variation confirm the potential benefit of using fiducial markers rather than bony anatomy for daily online position verification for pancreatic cancer patients.

Manipulating metal-oxide nanowires using counter-propagating optical line tweezers

Semiconducting nanowires, such as ZnO and Si, are used in the fields of nanophotonics and nanoelectronics. Optical tweezers offer the promise of flexible positional control of such particles in a liquid, but so far this has been limited to either manipulation close to the surface, or to axial trapping of nanowires. We show the three-dimensional trapping of ZnO and silica-coated Si nanowires in counter-propagating line tweezers, and demonstrate translational and rotational in-plane manipulation, away from the surfaces. The high-refractive index particles investigated - ZnO wires (n~1.9) with varying lengths up to 20mum and 6-mum-long silica-coated Si wires (n =3.6) - could not be trapped in single-beam line traps. Opposite surface charges are used to fix the nanowires to a surface. Full translational and in-plane rotational control of semiconducting nanowires expands the possibilities to position individual wires in complex geometries significantly.

BEAM INTENSITY MODULATION TO REDUCE THE FIELD SIZES FOR CONFORMAL IRRADIATION OF LUNG TUMORS: A DOSIMETRIC STUDY

PURPOSE In conformal radiotherapy of lung tumors, penumbra broadening in lung tissue necessitates the use of larger field sizes to achieve the same target coverage as in a homogeneous environment. In an idealized model configuration, some fundamental aspects of field size reduction were investigated, both for the static situation and for a moving tumor, while maintaining the dose homogeneity in the target volume by employing a simple beam-intensity modulation technique. METHODS AND MATERIALS An inhomogeneous phantom, consisting of polystyrene, cork, and polystyrene layers, with a 6 x 6 x 6 cm3 polystyrene cube inside the cork representing the tumor, was used to simulate a lung cancer treatment. Film dosimetry experiments were performed for an AP-PA irradiation technique with 8-MV or 18-MV beams. Dose distributions were compared for large square fields, small square fields, and intensity-modulated fields in which additional segments increase the dose at the edge of the field. The effect of target motion was studied by measuring the dose distribution for the solid cube, displaced with respect to the beams. RESULTS For the 18-MV beam, the field sizes required to establish a sufficient target coverage are larger than for the 8-MV beam. For each beam energy, the mean dose in cork can significantly be reduced (at least a factor of 1.6) by decreasing the field size with 2 cm, while keeping the mean target dose constant. Target dose inhomogeneity for these smaller fields is limited if the additional edge segments are applied for 8% of the number of monitor units given with the open fields. The target dose distribution averaged over a motion cycle is hardly affected if the target edge does not approach the field edge to within 3 mm. CONCLUSIONS For lung cancer treatment, a beam energy of 8 MV is more suitable than 18 MV. The mean lung dose can be significantly reduced by decreasing the field sizes of conformal fields. The smaller fields result in the same biological effect to the tumor if the mean target dose is kept constant. Intensity modulation can be employed to maintain the same target dose homogeneity for these smaller fields. As long as the target (with a 3 mm margin) stays within the field portal, application of a margin for target motion is not necessary.

Power spectral analysis for optical trap stiffness calibration from high-speed camera position detection with limited bandwidth

The use of camera imaging enables trap calibration for multiple particles simultaneously. For stiff traps, however, blur from image integration time affects the detected particle positions significantly. In this paper we use power spectral analysis to calibrate stiff optical traps, taking the effects of blur, aliasing and position detection error into account, as put forward by Wong and Halvorsen [Opt. Express 14, 12517 (2006)]. We find agreement with simultaneously obtained photodiode data and the expected relation of corner frequency fc with laser power, up to fc = 3.6 kHz for a Nyquist frequency of 1.25 kHz. Spectral analysis enables easy identification of the contribution of noise. We demonstrate the utility of our approach with simultaneous calibration of multiple holographic optical traps.

Differences in respiratory-induced pancreatic tumor motion between 4D treatment planning CT and daily cone beam CT, measured using intratumoral fiducials

Abstract Background. In radiotherapy, the magnitude of respiratory-induced tumor motion is often measured using a single four-dimensional computed tomography (4DCT). This magnitude is required to determine the internal target volume. The aim of this study was to compare the magnitude of respiratory-induced motion of pancreatic tumors on a single 4DCT with the motion on daily cone beam CT (CBCT) scans during a 3–5-week fractionated radiotherapy scheme. In addition, we investigated changes in the respiratory motion during the treatment course. Material and methods. The mean peak-to-peak motion (i.e. magnitude of motion) of pancreatic tumors was measured for 18 patients using intratumoral gold fiducials visible on CBCT scans made prior to each treatment fraction (10–27 CBCTs per patient; 401 CBCTs in total). For each patient, these magnitudes were compared to the magnitude measured on 4DCT. Possible time trends were investigated by applying linear fits to the tumor motion determined from daily CBCTs as a function of treatment day. Results. We found a significant (p ≤ 0.01) difference between motion magnitude on 4DCT and on CBCT in superior-inferior, anterior-posterior and left-right direction, in 13, 9 and 12 of 18 patients, respectively. In the anterior- posterior and left-right direction no fractions had a difference ≥ 5 mm. In the superior-inferior direction the difference was ≥ 5 mm for 17% of the 401 fractions. In this direction, a significant (p ≤ 0.05) time trend in tumor motion was observed in 4 of 18 patients, but all trends were small (− 0.17–0.10 mm/day) and did not explain the large differences in motion magnitude between 4DCT and CBCT. Conclusion. A single measurement of the respiratory-induced motion magnitude of pancreatic tumors using 4DCT is often not representative for the magnitude during daily treatment over a 3–5-week radiotherapy scheme. For this patient group it may be beneficial to introduce breath-hold to eliminate respiratory-induced tumor motion.

EUS-guided fiducial markers placement with a 22-gauge needle for image-guided radiation therapy in pancreatic cancer

DISCLOSURE: The following authors disclosed financial relationships relevant to this publication: Dr Fockens is a consultant to Olympus, Fujifilm, Boston Scientific, and Cook. Dr Bel collaborates on projects for Elekta. Dr van Hooft is a consultant to Cook Ireland Ltd and Boston Scientific. All other authors disclosed no financial relationships relevant to this publication. Dr van der Horst and Eelco Lens were supported by the Foundation Bergh in het Zadel through the Dutch Cancer Society (KWF Kankerbestrijding) project no. UVA 2011-5271.

High trapping forces for high-refractive index particles trapped in dynamic arrays of counterpropagating optical tweezers

We demonstrate the simultaneous trapping of multiple high-refractive index (n > 2) particles in a dynamic array of counterpropagating optical tweezers in which the destabilizing scattering forces are canceled. These particles cannot be trapped in single-beam optical tweezers. The combined use of two opposing high-numerical aperture objectives and micrometer-sized high-index titania particles yields an at least threefold increase in both axial and radial trap stiffness compared to silica particles under the same conditions. The stiffness in the radial direction is obtained from measured power spectra; calculations are given for both the radial and the axial force components, taking spherical aberrations into account. A pair of acousto-optic deflectors allows for fast, computer-controlled manipulation of the individual trapping positions in a plane, while the method used to create the patterns ensures the possibility of arbitrarily chosen configurations. The manipulation of high-index particles finds its application in, e.g., creating defects in colloidal photonic crystals and in exerting high forces with low laser power in, for example, biophysical experiments.