Patient positioning in radiotherapy based on surface imaging using time of flight cameras.

PURPOSE: To evaluate the patient positioning accuracy in radiotherapy using a stereo-time of flight (ToF)-camera system. METHODS: A system using two ToF cameras was used to scan the surface of the patients in order to position them daily on the treatment couch. The obtained point clouds were registered to (a) detect translations applied to the table (intrafraction motion) and (b) predict the displacement to be applied in order to place the patient in its reference position (interfraction motion). The measures provided by this system were compared to the effectively applied translations. The authors analyzed 150 fractions including lung, pelvis/prostate, and head and neck cancer patients. RESULTS: The authors obtained small absolute errors for displacement detection: 0.8 ± 0.7, 0.8 ± 0.7, and 0.7 ± 0.6 mm along the vertical, longitudinal, and lateral axes, respectively, and 0.8 ± 0.7 mm for the total norm displacement. Lung cancer patients presented the largest errors with a respective mean of 1.1 ± 0.9, 0.9 ± 0.9, and 0.8 ± 0.7 mm. CONCLUSIONS: The proposed stereo-ToF system allows for sufficient accuracy and faster patient repositioning in radiotherapy. Its capability to track the complete patient surface in real time could allow, in the future, not only for an accurate positioning but also a real time tracking of any patient intrafraction motion (translation, involuntary, and breathing).

Technical Note: Evaluation of the systematic accuracy of a frameless, multiple image modality guided, linear accelerator based stereotactic radiosurgery system.

PURPOSE: To evaluate the total systematic accuracy of a frameless, image guided stereotactic radiosurgery system. METHODS: The localization accuracy and intermodality difference was determined by delivering radiation to an end-to-end prototype phantom, in which the targets were localized using optical surface monitoring system (OSMS), electromagnetic beacon-based tracking (Calypso®), cone-beam CT, "snap-shot" planar x-ray imaging, and a robotic couch. Six IMRT plans with jaw tracking and a flattening filter free beam were used to study the dosimetric accuracy for intracranial and spinal stereotactic radiosurgery treatment. RESULTS: End-to-end localization accuracy of the system evaluated with the end-to-end phantom was 0.5 ± 0.2 mm with a maximum deviation of 0.9 mm over 90 measurements (including jaw, MLC, and cone measurements for both auto and manual fusion) for single isocenter, single target treatment, 0.6 ± 0.4 mm for multitarget treatment with shared isocenter. Residual setup errors were within 0.1 mm for OSMS, and 0.3 mm for Calypso. Dosimetric evaluation based on absolute film dosimetry showed greater than 90% pass rate for all cases using a gamma criteria of 3%/1 mm. CONCLUSIONS: The authors' experience demonstrates that the localization accuracy of the frameless image-guided system is comparable to robotic or invasive frame based radiosurgery systems.

Evaluation of a new six degrees of freedom couch for radiation therapy.

PURPOSE: The aim of this work is to evaluate the geometric accuracy of a prerelease version of a new six degrees of freedom (6DoF) couch. Additionally, a quality assurance method for 6DoF couches is proposed. METHODS: The main principle of the performance tests was to request a known shift for the 6DoF couch and to compare this requested shift with the actually applied shift by independently measuring the applied shift using different methods (graph paper, laser, inclinometer, and imaging system). The performance of each of the six axes was tested separately as well as in combination with the other axes. Functional cases as well as realistic clinical cases were analyzed. The tests were performed without a couch load and with a couch load of up to 200 kg and shifts in the range between -4 and +4 cm for the translational axes and between -3° and +3° for the rotational axes were applied. The quality assurance method of the new 6DoF couch was performed using a simple cube phantom and the imaging system. RESULTS: The deviations (mean ± one standard deviation) accumulated over all performance tests between the requested shifts and the measurements of the applied shifts were -0.01 ± 0.02, 0.01 ± 0.02, and 0.01 ± 0.02 cm for the longitudinal, lateral, and vertical axes, respectively. The corresponding values for the three rotational axes couch rotation, pitch, and roll were 0.03° ± 0.06°, -0.04° ± 0.12°, and -0.01° ± 0.08°, respectively. There was no difference found between the tests with and without a couch load of up to 200 kg. CONCLUSIONS: The new 6DoF couch is able to apply requested shifts with high accuracy. It has the potential to be used for treatment techniques with the highest demands in patient setup accuracy such as those needed in stereotactic treatments. Shifts can be applied efficiently and automatically. Daily quality assurance of the 6DoF couch can be performed in an easy and efficient way. Long-term stability has to be evaluated in further tests.

Development of a 3-D convolution/superposition algorithm for precise dose calculation in the skull.

In this paper an algorithm for calculating 3-D dose distributions within the brain is introduced and adapted to the demands of modem radiosurgery. The dose calculation with this model is based on a 3-D distribution of the primary photon intensity which is calculated with a ray casting algorithm. A prelocated matrix takes into account field sizes as well as modifying elements as collimator positions (MLC), blocks, wedges and compensators. Monte Carlo precalculated monoenergetic kernels from 0.1 MeV to 50 MeV were at our disposal. The components of the spectrum were either determined by deconvoluting depth dose curves measured in water or analyzed with a Ge-Li detector system in the case of 60Co. The calculated fluence distribution has to be superposed to the complete kernel containing the spatial energy deposition. Inhomogeneities and tissue interface phenomena (rhoe, Z) have been investigated. The divergence of the rays and the curved surface of the patient are taken into account. Assuming homogenous media, it is possible to shorten the computation time by using the Fast Fourier Transformation (FFT) delivering a first overview within seconds. The algorithm was evaluated and verified under specific conditions of small fields as used in radiosurgery and compared to dose measurements and Monte Carlo calculations. In using both the fast algorithm (FFT) for mainly homogenous conditions on one hand and the very precise superposition for inhomogeneous cases on the other, this algorithm can be a very helpful instrument especially for critical locations in the skull.

Experimental characterization and physical modelling of the dose distribution of scanned proton pencil beams.

In this paper we present the pencil beam dose model used for treatment planning at the PSI proton gantry, the only system presently applying proton therapy with a beam scanning technique. The scope of the paper is to give a general overview on the various components of the dose model, on the related measurements and on the practical parametrization of the results. The physical model estimates from first physical principles absolute dose normalized to the number of incident protons. The proton beam flux is measured in practice by plane-parallel ionization chambers (ICs) normalized to protons via Faraday-cup measurements. It is therefore possible to predict and deliver absolute dose directly from this model without other means. The dose predicted in this way agrees very well with the results obtained with ICs calibrated in a cobalt beam. Emphasis is given in this paper to the characterization of nuclear interaction effects, which play a significant role in the model and are the major source of uncertainty in the direct estimation of the absolute dose. Nuclear interactions attenuate the primary proton flux, they modify the shape of the depth-dose curve and produce a faint beam halo of secondary dose around the primary proton pencil beam in water. A very simple beam halo model has been developed and used at PSI to eliminate the systematic dependences of the dose observed as a function of the size of the target volume. We show typical results for the relative (using a CCD system) and absolute (using calibrated ICs) dosimetry, routinely applied for the verification of patient plans. With the dose model including the nuclear beam halo we can predict quite precisely the dose directly from treatment planning without renormalization measurements, independently of the dose, shape and size of the dose fields. This applies also to the complex non-homogeneous dose distributions required for the delivery of range-intensity-modulated proton therapy, a novel therapy technique developed at PSI.

Development of an interactive graphical user interface for therapy simulation.

Because of the ongoing development to more complex non-coplanar techniques in radiotherapy, the use of modem computer graphics while designing a dose plan becomes increasingly essential and more important. In this paper, we describe a concept to simulate 3D conformal treatment techniques on the computer. All important components of the treatment device and relevant patient structures are mapped to an internal model, which allows simulation of motion sequences as well as the interactive adjustment of treatment parameters. The intention of this user interface is to save time by using mainly graphical modules in the optimization process instead of running through the dose calculation every time.

High precision radiosurgery and technical standards.

BACKGROUND: A high degree of precision and accuracy in radiosurgery is a fundamental requirement for therapeutic success. Small radiation fields and steep dose gradients are clinically applied thus necessitating a dedicated quality assurance program in order to guarantee dosimetric and geometric accuracy. MATERIAL AND METHODS: A detailed analysis of the course of treatment independent of the irradiation technique used results in the so-called chain of uncertainties in radiosurgery (immobilisation, imaging, treatment planning system, definition of regions of interest, mechanical accuracy, dose planning, dose verification). Each link in this chain is analysed for accuracy and the established quality assurance procedures are discussed. A "System Test" was used to check the whole chain of uncertainties simultaneously. RESULTS: The tests described are compatible with published reports on quality assurance in radiosurgery. In terms of accuracy the weakest link in the chain of uncertainties is stereotactic MR imaging. Geometric overall accuracy measured in the "System Test" is less than 0.7 mm. CONCLUSION: The established quality assurance routines have clinically been validated. MR imaging dominates geometric overall accuracy in radiosurgery, which can be limited to less than 1 mm by an adequate quality assurance protocol.

Quality assurance in stereotactic radiosurgery/radiotherapy according to DIN 6875-1.

The new DIN ('Deutsche Industrie-Norm') 6875-1, which is currently being finalised, deals with quality assurance (QA) criteria and tests methods for linear accelerator and Gamma Knife stereotactic radiosurgery/radiotherapy including treatment planning, stereotactic frame and stereotactic imaging and a system test to check the whole chain of uncertainties. Our existing QA program, based on dedicated phantoms and test procedures, has been refined to fulfill the demands of this new DIN. The radiological and mechanical isocentre corresponded within 0.2 mm and the measured 50% isodose lines were in agreement with the calculated ones within less than 0.5 mm. The measured absorbed dose was within 3%. The resultant output factors measured for the 14-, 8- and 4-mm collimator helmet were 0.9870 +/- 0.0086, 0.9578 +/- 0.0057 and 0.8741 +/- 0.0202, respectively. For 170 consecutive tests, the mean geometrical accuracy was 0.48 +/- 0.23 mm. Besides QA phantoms and analysis software developed in-house, the use of commercially available tools facilitated the QA according to the DIN 6875-1 with which our results complied.

Suppression of post-vitrectomy lens changes in the rabbit by novel benzopyranyl esters and amides.

This study reports for the first time a therapeutic modality for the suppression of posterior subcapsular cataract (PSC) formation in an animal model (rabbit) of vitrectomy. This therapeutic modality may also have the potential to attenuate/prevent the high incidence of loss of vision due to cataract formation in patients that undergo vitrectomy. Unilateral, partial vitrectomy was performed on 2.5 month old Dutch Belted rabbits with vitreous replaced by either commercially available BSS((R)) or BSS PLUS((R)) (n=16). Alternatively, vitreous was replaced with a proprietary, modified BSS PLUS((R)) irrigating solution containing 1.25 microM AL-8417 (n=12), 5.0 microM AL-12615 (n=5) or 5.0 microM AL-17052 (n=9). Age matched, non-operated rabbits were used as controls (n=16). Lenses were analysed by correlative structural (light, scanning electron microscopic and three-dimensional computer-assisted drawings) and optical (low power helium-neon laser scan) quality analysis 6 months following surgery. Results demonstrate that vitreous replacement with an irrigating solution that contains the ester-linked benzopyran, AL-8417, the amide-linked benzopyran pro-drug, AL-17052, or its active metabolite, AL-12615, prevented abnormal post-vitrectomy lens growth, or fiber formation. Focal length variability (FLV) assessments (sharpness of focus) confirmed the beneficial drug effects detected morphologically, with FLV being essentially equal to that of age-matched, non-surgical controls. In contrast, lenses of animals with vitreous replaced solely with BSS((R)) or BSS PLUS((R)) exhibited significantly higher FLV than both age-matched controls and animals that underwent vitrectomy with drug-containing irrigating solutions. The ability of AL-8417, AL-17052 and its active metabolite, AL-12615, to suppress vitrectomy-induced posterior lens fiber changes appears to reside in their unique pharmacological profile, acting as antioxidant, anti-inflammatory and cytostatic agents.

[Palliative treatment of brain metastases with gamma knife]. / Palliative Behandlung von Hirnmetastasen mit dem Gamma Knife.

The gamma knife is a stereotactic radiosurgery device which allows well defined, deep seated brain tumors or arteriovenous malformations with a maximal volume of about 25 ccm and a diameter not greater than 3.5 cm, to be treated in a single session under local anesthesia. The gamma knife offers an alternative treatment method to the classical approach of treating brain metastases by surgical excision and/or whole brain radiotherapy. The advantages of this technique are evident: the method is non-invasive, the treatment is carried out in a single session with a very short hospitalisation of two to three days, it is exempt from physical and psychical stress, the head does not need to be shaved and no hair loss occurs, a good quality of life is obtained for a reasonably prolonged survival time and it offers an economically favourable treatment method. Up to December 1999, over 30,000 patients suffering from brain metastases have been treated worldwide using the gamma knife. In Zürich, from September 1994 to December 2000 140 received this treatment. In the literature selection criteria may differ, and this may have determined some of differences in outcome. However, our results are comparable with those in the majority of publications with an average survival time of 263 days and a maximum survival of 1080 days. Good prognostic factors for survival and local control of brain metastases are a Karnofsky Performance Scale Score approaching 90 to 100, but not lower than 70, tumour volume, controlled primary cancer, and absence or stable extracranial metastases.

The effect of partial vitrectomy on blood-ocular barrier function in the rabbit.

PURPOSE: To compare ocular vascular permeability in the rabbit after vitrectomy as assessed by contrast-enhanced magnetic imaging (CE-MRI) and measurements of aqueous and vitreous humor protein concentration. METHODS: Partial vitrectomies were performed, irrigating with BSS or BSS PLUS. Post-operative vascular leakage was determined by CE-MRI following intravenous administration of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Aqueous and vitreous protein concentrations were quantified by standard biochemical assay. ERG evaluations were performed on postoperative days 1, 3, and 7. RESULTS: Using BSS as irrigant, breakdown of the inner blood-retinal barrier (BRB) occurred in 4/7 eyes on post-operative day 1. The rate of Gd-DTPA leakage was significantly greater on postoperative day 1 than that in unoperated, control eyes, but declined approximately 50% by day 3. At both time points, outer BRB breakdown was restricted to the sclerotomy wounds. No BRB leakage was detectable in control eyes. Blood-aqueous barrier (BAB) leakage was bilateral on day 1. Significantly greater Gd-DTPA leakage occurred in the operated eye than in the nonsurgical contralateral eye. On day 3, approximately 40% bilateral reduction in leakage indicated resolution of BAB leakage. Notably, Gd-DTPA leakage of the BAB and BRB was significantly reduced in the BSS PLUS treated group. In contrast to MRI assessments, protein concentrations of the aqueous and vitreous in the surgical eye showed no detectable differences between BSS and BSS PLUS. Concurrent with the transient loss of ocular barrier function, ERG responses also declined. However, by day 7 greater than 90% recovery was noted in BSS PLUS treated animals but not in the BSS treatment group. CONCLUSIONS: CE-MRI is capable of detecting subtle changes in vascular permeability following ocular surgery. Advantages of using BSS PLUS compared to BSS as the irrigating solution can be detected using this technique. BSS PLUS's protection of barrier function is consistent with a rapid recovery in retinal function not observed in BSS treated eyes.

The relationship between rabbit lens optical quality and sutural anatomy after vitrectomy.

This study was conducted first, to characterize structural changes in rabbit lenses after vitrectomy; and second, to assess whether such changes correlate with a quantifiable compromise in optical function. Unilateral, partial vitrectomies were performed on 2.5 month old Dutch Belted rabbits (n = 64). Age matched non-operated rabbits (n = 32) were used as controls. Lenses were analysed by correlative structural (light, scanning electron microscopic and three-dimensional computer-assisted drawings) and optical (low power helium-neon laser scan) analysis at 1.5, 3, 6 and 12 months post-surgery (n = 16 lenses from operated animals and n = 8 lenses from non-operated controls at each time point). Results demonstrate that in rabbits lens growth, or fiber formation, is compromised after vitrectomy. From 1.5 to 12 months after surgery, lenses had progressively more crooked posterior line sutures with sub-branches of increasing size and number in successive growth shells. Quantification of lens optical quality specifically along and/or between these atypical suture branches and sub-branches revealed a significant increase in focal length variability (sharpness of focus) after vitrectomy. A peripheral zone of fibers with abnormal posterior ends was produced surrounding the pre-surgical lens mass. This additional zone of aberrant fibers was associated with a quantifiable degradation in lens optics. Studies on the prevention of post-vitrectomy lens changes in this rabbit model may yield useful information applicable to the human condition.

Octreotide may act as a radioprotective agent in acromegaly.

Clinical experience shows that an increasing number of patients undergoing radiation treatment for recurring acromegaly or acromegaly persisting after surgery are treated with octreotide. We, therefore, performed a follow-up study of patients undergoing stereotactic radiosurgery (Gamma Knife) to determine whether this medication has an influence on the ultimate result of radiation therapy in either a positive or negative sense. It has been suggested that the combination of radiation with antisecretory drugs may increase the effectiveness of radiation. A follow-up study of 31 patients suffering from recurrent acromegaly and acromegaly persisting after surgery, and who had been treated with stereotactic radiosurgery, showed that patients treated with octreotide at the time of radiation application simultaneously reached a normal level of growth hormone and insulin-like growth factor-I only after a significantly longer interval than patients who did not receive the drug. The two groups of patients did not demonstrate significant differences in the main clinical findings (age, sex, target volume, radiation dose, baseline growth hormone, and baseline insulin-like growth factor-I).

VOLUMESERIES: a software tool for target volume follow-up studies with computerized tomography and magnetic resonance imaging. Technical note.

In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume of the lesion are measured. To determine the lesion volume without using stereotactically defined images, the software program VOLUMESERIES has been developed. VOLUMESERIES is a personal computer-based image analysis tool. Acquired DICOM CT scans and MR image series can be visualized. The region of interest is contoured with the help of the mouse, and then the system calculates the volume of the contoured region and the total volume is given in cubic centimeters. The defined volume is also displayed in reconstructed sagittal and coronal slices. In addition, distance measurements can be performed to measure tumor extent. The accuracy of VOLUMESERIES was checked against stereotactically defined images in the Leksell GammaPlan treatment planning program. A discrepancy in target volumes of approximately 8% was observed between the two methods. This discrepancy is of lesser interest because the method is used to determine the course of the target volume over time, rather than the absolute volume. Moreover, it could be shown that the method was more sensitive than the tumor diameter measurements currently in use. VOLUMESERIES appears to be a valuable tool for assessing residual lesion volume on follow-up images after gamma knife radiosurgery while avoiding the need for stereotactic definition.

Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy.

OBJECT: The authors tested the assumption that gamma knife radiosurgery is more effective than fractionated radiotherapy for the treatment of patients with acromegaly who have undergone unsuccessful resective surgery. Untreated and uncured acromegaly causes illness and death. Acromegalic patients in whom growth hormone and, particularly, insulin-like growth factor I are not normalized must undergo further treatment. METHODS: After unsuccessful operations, 16 patients suffering from recurrent and uncured acromegaly underwent stereotactic radiosurgery (25 Gy to the tumor margin, 50 Gy maximum), the outcome of which was compared with the result obtained in 50 patients who received fractionated radiotherapy (40 Gy). The cumulative distribution functions of the two groups (Kaplan-Meier estimate) differed significantly (p < 0.0001 in the log-rank test of Mantel). The mean time to simultaneous normalization of both parameters was 1.4 years in the group treated with the gamma knife and 7.1 years in the group treated with fractionated radiotherapy. CONCLUSIONS: The authors suggest the use of stereotactic radiosurgery as the preferred treatment for recurrent acromegaly resulting from unsuccessfully resected tumors.

[Gamma knife radiosurgery in neurosurgery]. / Das Gamma-Knife im Dienste der Neurochirurgie.

The gamma knife is a stereotactic radiosurgery device which allows well defined, deep seated brain tumors, or arteriovenous malformations having a diameter of less than 3 cm, to be treated in a single session under local anesthesia. This technique, which was first described over 40 years ago, has undergone major development in recent years and is the most commonly used method for radiosurgery worldwide. The principle relies on the over-lapping of narrow collimated beams from 201 cobalt-60 sources. The technique, which was introduced into Switzerland in September 1994, has rapidly gained recognition. 184 patients have been treated by 30 April 1997. An average follow-up period of 15 months is much too short for analysis of patients treated by radiosurgery. However, our series of benign tumors shows stabilization of volume in the first few months followed by a slow reduction of the tumor volume, in all but two cases. The gamma knife represents the treatment of choice for recurrent and unsuccessfully operated patients with endocrine active pituitary adenomas. With brain metastases, a rapid reduction in tumor volume is seen in the first few weeks in the majority of cases. The tumor volume may then remain stable or reduce further until complete disappearance. In the case of arteriovenous malformations complete obliteration of the nidus is not seen, on average, for 2-3 years. Individual patient follow-up studies illustrate these results. To date our results have shown zero morbidity and mortality. International statistics from 58,766 cases (as of December 1996) from 77 gamma knife centers demonstrate the value of this technique as a complement or, depending on the indication, an alternative to classical microsurgery.

The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization.

The new proton therapy facility is being assembled at the Paul Scherrer Institute (PSI). The beam delivered by the PSI sector cyclotron can be split and brought into a new hall where it is degraded from 590 MeV down to an energy in the range of 85-270 MeV. A new beam line following the degrader is used to clean the low-energetic beam in phase space and momentum band. The analyzed beam is then injected into a compact isocentric gantry, where it is applied to the patient using a new dynamic treatment modality, the so-called spot-scanning technique. This technique will permit full three-dimensional conformation of the dose to the target volume to be realized in a routine way without the need for individualized patient hardware like collimators and compensators. By combining the scanning of the focused pencil beam within the beam optics of the gantry and by mounting the patient table eccentrically on the gantry, the diameter of the rotating structure has been reduced to only 4 m. In the article the degrees of freedom available on the gantry to apply the beam to the patient (with two rotations for head treatments) are also discussed. The devices for the positioning of the patient on the gantry (x rays and proton radiography) and outside the treatment room (the patient transporter system and the modified mechanics of the computer tomograph unit) are briefly presented. The status of the facility and first experimental results are introduced for later reference.