Improving MRT image quality in patients with movement disorders.

OBJECTIVE: In order to improve image quality in a simultaneous fMRI-EEG study with patients suffering from the involuntary movements typical for Huntington's disease, the aim was to develop a technique for immobilizing the heads of our patients inside an MRI head coil. METHODS: We modified a mask technique previously used for reliable repositioning in temporally fractionated radiotherapy. The mask was tested in three patients with Huntington's disease, acquiring structural and functional MR images with simultaneous EEG with and without the mask. RESULTS: Image as well as EEG signal quality were significantly improved in patients wearing the mask. However, the image quality with mask was comparable to acquisitions from patients without movement disorders only in patients with light to moderate dyskinesia. Although image quality was also significantly improved in a patient suffering from severe dyskinesia with quasi-continuous involuntary movements, the quality of both the MR images as well as the EEG signal was lower than what would be expected in a healthy control person. CONCLUSION: We have succeeded in developing a mask that fits into the MRI head coil, does not disturb the MRI signal, and significantly improves both fMRI and EEG signal quality.

On the accuracy of isocenter verification with kV imaging in stereotactic radiosurgery.

BACKGROUND AND PURPOSE: Modern medical linear accelerators (linacs) are equipped with X-ray systems, which allow to check the patient's position just prior to treatment. Their usefulness for stereotactic radiosurgery (SRS) depends on how accurately they allow to determine the deviation between the actual and planned isocenter positions. This accuracy was investigated with measurements using two different phantoms (Figures 1 and 2). MATERIAL AND METHODS: After precisely aligning a phantom onto the linac isocenter, two perpendicular X-rays or a cone-beam CT (CBCT) are taken, and the isocenter position is deduced from this data. The deviation of the thereby gained position from the setup isocenter is taken as a measure for the uncertainty of this method. RESULTS: Isocenter verification with two orthogonal X-rays (Figure 4) achieves accuracies of better than 1 mm (Table 3). The distance between the isocenters of the CBCT and the linac (Figure 3) is in the order of 1 mm, but remains constant on the time scale of 1 week (Table 1) and may therefore be taken into account. The uncertainty after correction is below 0.2 mm. CONCLUSION: kV imaging with the patient in treatment position allows to verify the isocenter position with submillimeter precision, and therefore offers a supplemental test, suitable for SRS, which takes all positional uncertainties into account.

A deep conical agarose microwell array for adhesion independent three-dimensional cell culture and dynamic volume measurement.

Multicellular spheroids represent a well-established 3D model to study healthy and diseased cells in vitro. The use of conventional 3D cell culture platforms for the generation of multicellular spheroids is limited to cell types that easily self-assemble into spheroids because less adhesive cells fail to form stable aggregates. A high-precision micromoulding technique developed in our laboratory produces deep conical agarose microwell arrays that allow the cultivation of uniform multicellular aggregates, irrespective of the spheroid formation capacity of the cells. Such hydrogel arrays warrant a steady nutrient supply for several weeks, permit live volumetric measurements to monitor cell growth, enable immunohistochemical staining, fluorescence-based microscopy, and facilitate immediate harvesting of cell aggregates. This system also allows co-cultures of two distinct cell types either in direct cell-cell contact or at a distance as the hydrogel permits diffusion of soluble compounds. Notably, we show that co-culture of a breast cancer cell line with bone marrow stromal cells enhances 3D growth of the cancer cells in this system.

Single punch, double biopsy.

OBJECTIVE: In lethal primary metastatic prostate cancer, biopsy material is often the only accessible cancer tissue. Lack of tissue quantity limited the use of biopsy cores for analyzing higher numbers of molecular markers and standard histopathologic evaluation for clinical diagnosis simultaneously. Recent advances in single cell analytics have paved the way to characterize a tumor in more depth from minute input material such as biopsies. We therefore aimed to develop a biopsy needle, which generates two cores side by side from the same punch: one for standard histopathologic analysis to allow for routine diagnostics and the second one for single cell analytics. METHODS: On the basis of a conventional punch biopsy needle we have milled two parallel longitudinal rifts into the needles shat which are separated by a 100 µm thick metal sheet. Each rift can harbor a single tissue core. RESULTS: Two cores from the same punch were generated reproducibly from a radical prostatectomy specimen and showed congruent results in histopathologic analysis. Both cores yielded equally sufficient material for standard H&E staining and histopathological evaluation. CONCLUSION: Our modified biopsy system will allow for simultaneous acquisition of tissue cores for diagnostic and scientific analysis from solid tumors or metastatic sites.

[In-phantom dosimetric measurements as quality control for brachytherapy: System check and constancy check]. / Messungen im Festkörperphantom als Qualitätskontrolle in der Brachytherapie - Systemprüfung und Konstanzprüfung.

In brachytherapy dosimetric measurements are difficult due to the inherent dose-inhomogenieties. Typically in routine clincal practice only the nominal dose rate is determined for computer controlled afterloading systems. The region of interest lies close to the source when measuring the spatial dose distribution. In this region small errors in the postioning of the detector, and its finite size, lead to large measurement uncertainties that exacerbate the routine dosimetric control of the system in the clinic. The size of the measurement chamber, its energy dependence, and the directional dependence of the measurement apparatus are the factors which have a significant influence on dosimetry. Although ionisation chambers are relatively large, they are employed since similar chambers are commonly found on clincal brachytherapy units. The dose is determined using DIN 6800 [11] since DIN 6809-2 [12], which deals with dosimetry in brachytherapy, is antiquated and is currently in the process of revision. Further information regarding dosimetry for brachytherapy can be found in textbooks [1] and [2]. The measurements for this work were performed with a HDR (High-Dose-Rate) (192)Ir source, type mHDR V2, and a Microselectron Afterloader V2 both from Nucletron/Elekta. In this work two dosimetric procedures are presented which, despite the aforemention difficulties, should assist in performing checks of the proper operation of the system. The first is a system check that measures the dose distribution along a line and is to be performed when first bringing the afterloader into operation, or after significant changes to the system. The other is a dosimetric constancy check, which with little effort can be performed monhtly or weekly. It simultaneously verifies the positioning of the source at two positions, the functionality of the system clock and the automatic re-calculation of the source activity.

Feasibility of a semi-automated contrast-oriented algorithm for tumor segmentation in retrospectively gated PET images: phantom and clinical validation.

PET/CT plays an important role in radiotherapy planning for lung tumors. Several segmentation algorithms have been proposed for PET tumor segmentation. However, most of them do not take into account respiratory motion and are not well validated. The aim of this work was to evaluate a semi-automated contrast-oriented algorithm (COA) for PET tumor segmentation adapted to retrospectively gated (4D) images. The evaluation involved a wide set of 4D-PET/CT acquisitions of dynamic experimental phantoms and lung cancer patients. In addition, segmentation accuracy of 4D-COA was compared with four other state-of-the-art algorithms. In phantom evaluation, the physical properties of the objects defined the gold standard. In clinical evaluation, the ground truth was estimated by the STAPLE (Simultaneous Truth and Performance Level Estimation) consensus of three manual PET contours by experts. Algorithm evaluation with phantoms resulted in: (i) no statistically significant diameter differences for different targets and movements (Δφ = 0.3 ± 1.6 mm); (ii) reproducibility for heterogeneous and irregular targets independent of user initial interaction and (iii) good segmentation agreement for irregular targets compared to manual CT delineation in terms of Dice Similarity Coefficient (DSC = 0.66 ± 0.04), Positive Predictive Value (PPV = 0.81 ± 0.06) and Sensitivity (Sen. = 0.49 ± 0.05). In clinical evaluation, the segmented volume was in reasonable agreement with the consensus volume (difference in volume (%Vol) = 40 ± 30, DSC = 0.71 ± 0.07 and PPV = 0.90 ± 0.13). High accuracy in target tracking position (ΔME) was obtained for experimental and clinical data (ΔME(exp) = 0 ± 3 mm; ΔME(clin) 0.3 ± 1.4 mm). In the comparison with other lung segmentation methods, 4D-COA has shown the highest volume accuracy in both experimental and clinical data. In conclusion, the accuracy in volume delineation, position tracking and its robustness on highly irregular target movements, make this algorithm a useful tool for 4D-PET based volume definition for radiotherapy planning of lung cancer and may help to improve the reproducibility in PET quantification for therapy response assessment and prognosis.

[Long term registration of linear accelerator parameters for quality assurance in stereotaxic radiosurgery]. / Langzeitverfolgung von Linearbeschleunigerparametern zur Qualitätssicherung stereotaktischer Strahlenbehandlungen.

Long-term observations of mechanical parameters have been performed in Freiburg for the last 7 years within the quality assurance of stereotactic irradiation at linear accelerators. The deviations between the laser indication and the position of the beam isocentre are recorded, as well as parameters for the stability of the couch rotation and the additional devices for patient adjustment and beam collimation. The deviations are used for the correction of the calculated isocentre coordinates. The long-term observation of the measured values and their standard deviations allow conclusions about the quality of the measuring procedure itself, the laser adjustment, the extension of the isocentre sphere, as well as the mechanical slackness of the treatment couch and the fixation device of the stereotactic ring. The standard deviations of the isocentre position were within 0.3 to 0.8 mm, those of the measurement quality approximately 0.2 mm. The analysis of long-term observation has contributed to improvements of the equipment and of quality assurance procedures.