MRIgRT head and neck anthropomorphic QA phantom: Design, development, reproducibility, and feasibility study.

PURPOSE: The purpose of this paper was to design, manufacture, and evaluate a tissue equivalent, dual magnetic resonance/computed tomography (MR/CT) visible anthropomorphic head and neck (H&N) phantom. This phantom was specially designed as an end-to-end quality assurance (QA) tool for MR imaging guided radiotherapy (MRIgRT) systems participating in NCI-sponsored clinical trials. METHOD: The MRIgRT H&N phantom was constructed using a water-fillable acrylic shell and a custom insert that mimics an organ at risk (OAR) and target structures. The insert consists of a primary and secondary planning target volume (PTV) manufactured of a synthetic Clear Ballistic gel, an acrylic OAR and surrounding tissue fabricated using melted Superflab. Radiochromic EBT3 film and thermoluminescent detectors (TLDs) were used to measure the dose distribution and absolute dose, respectively. The phantom was evaluated by conducting an end-to-end test that included: imaging on a GE Lightspeed CT simulator, planning on Monaco treatment planning software (TPS), verifying treatment setup with MR, and irradiating on Elekta's 1.5 T Unity MR linac system. The phantom was irradiated three times using the same plan to determine reproducibility. Three institutions, equipped with either ViewRay MRIdian 60 Co or ViewRay MRIdian Linac, were used to conduct a feasibility study by performing independent end-to-end studies. Thermoluminescent detectors were evaluated in both reproducibility and feasibility studies by comparing ratios of measured TLD to reported TPS calculated values. Radiochromic film was used to compare measured planar dose distributions to expected TPS distributions. Film was evaluated by using an in-house gamma analysis software to measure the discrepancies between film and TPS. RESULTS: The MRIgRT H&N phantom on the Unity system resulted in reproducible TLD doses (SD < 1.5%). The measured TLD to calculated dose ratios for the Unity system ranged from 0.94 to 0.98. The Viewray dose result comparisons had a larger range (0.95-1.03) but these depended on the TPS dose calculations from each site. Using a 7%/4 mm gamma analysis, Viewray institutions had average axial and sagittal passing rates of 97.3% and 96.2% and the Unity system had average passing rates of 97.8% and 89.7%, respectively. All of the results were within the Imaging and Radiation Oncology Core in Houston (IROC-Houston) standard credentialing criteria of 7% on TLDs, and >85% of pixels passing gamma analysis using 7%/4 mm on films. CONCLUSIONS: An MRIgRT H&N phantom that is tissue equivalent and visible on both CT and MR was developed. The results from initial reproducibility and feasibility testing of the MRIgRT H&N phantom using the tested MGIgRT systems suggests the phantom's potential utility as a credentialing tool for NCI-clinical trials.

MRIgRT dynamic lung motion thorax anthropomorphic QA phantom: Design, development, reproducibility, and feasibility study.

PURPOSE: To design, manufacture, and evaluate a dynamic magnetic resonance imaging/computed tomography (MRI/CT)-compatible anthropomorphic thorax phantom used to credential MR image-guided radiotherapy (MRIgRT) systems participating in NCI-sponsored clinical trials. METHOD: The dynamic anthropomorphic thorax phantom was constructed from a water-fillable acrylic shell that contained several internal structures representing radiation-sensitive organs within the thoracic region. A custom MR/CT visible cylindrical insert was designed to simulate the left lung with a centrally located tumor target. The surrounding lung tissue was constructed from a heterogeneous in-house mixture using petroleum jelly and miniature (2-4 mm diameter) styrofoam balls and the tumor structure was manufactured from liquid PVC plastic. An MR conditional pneumatic system was developed to allow the MRIgRT insert to move in similar inhale/exhale motions. TLDs and radiochromic EBT3 film were inserted into the phantom to measure absolute point doses and dose distributions, respectively. The dynamic MRIgRT thorax phantom was evaluated through a reproducibility study and a feasibility study. Comprehensive end-to-end examinations were done where the phantom was imaged on a CT, an IMRT treatment plan was created and an MR image was captured to verify treatment setup. Then, the phantom was treated on an MRIgRT system. The reproducibility study evaluated how well the phantom could be reproduced in an MRIgRT system by irradiating three times on an Elekta's 1.5 T Unity system. The phantom was shipped to three independent institutions and was irradiated on either an MRIdian cobalt-60 (60 Co) or an MRIdian linear accelerator system. Treatment evaluations used TLDs and radiochromic film to compare the planned treatment reported on the treatment planning software against the measured dose on the dosimeters. RESULTS: The phantom on the Unity system had reproducible TLD doses measurements (SD < 1.5%). The measured TLD to calculated dose ratios from the reproducibility and feasibility studies ranged from 0.93 to 1.01 and 0.96 to 1.03, respectively. Using a 7%/5 mm gamma analysis criteria, the reproducibility and feasibility studies resulted in an average passing rate of 93.3% and 96.8%, respectively. No difference was noted in the results between the MRIdian 60 Co and MRIdian 6 MV linac delivery to the phantom and all treatment evaluations were within IROC-Houston's acceptable criterion. CONCLUSIONS: A dosimetrically tissue equivalent, CT/MR visible, motion-enabled anthropomorphic MRIgRT thorax phantom was constructed to simulate a lung cancer patient and was evaluated as an appropriate NIH credentialing tool used for MRIgRT systems.

Investigation of TLD and EBT3 performance under the presence of 1.5T, 0.35T, and 0T magnetic field strengths in MR/CT visible materials.

PURPOSE: The aim of this study was to investigate thermoluminescent dosimeters (TLD) and radiochromic EBT3 film inside MR/CT visible geometric head and thorax phantoms in the presence of: 0, 0.35, and 1.5 T magnetic fields. METHODS: Thermoluminescent Dosimeters reproducibility studies were examined by irradiating IROC-Houston's TLD acrylic block five times under 0 and 1.5 T configurations of Elekta's Unity system and three times under 0 and 0.35 T configurations of ViewRay's MRIdian Cobalt-60 (60 Co) system. Both systems were irradiated with an equivalent 10 × 10 cm2 field size, and a prescribed dose of 3 Gy to the maximum depth deposition (dmax). EBT3 film and TLDs were investigated using two geometrical Magnetic Resonance (MR)-guided Radiation Therapy (MRgRT) head and thorax phantoms. Each geometrical phantom had eight quadrants that combined to create a centrally located rectangular tumor (3 × 3 × 5 cm3 ) surrounded by tissue to form a 15 × 15 × 15 cm3 cubic phantom. Liquid polyvinyl chloride plastic and Superflab were used to simulate the tumor and surrounding tissue in the head phantom, respectively. Synthetic ballistic gel and a heterogeneous in-house mixture were used to construct the tumor and surrounding tissue in the thorax phantom, respectively. EBT3 and double-loaded TLDs were used in the phantoms to compare beam profiles and point dose measurements with and without magnetic fields. GEANT4 Monte Carlo simulations were performed to validate the detectors for both Unity 0 T/1.5 T and MRIdian 0 T/0.35 T configurations. RESULTS: Average TLD block measurements which, compared the magnetic field effects (magnetic field vs 0 T) on the Unity and MRIdian systems, were 0.5% and 0.6%, respectively. The average ratios between magnetic field effects for the geometric thorax and head phantoms under the Unity system were -0.2% and 1.6% and for the MRIdian system were 0.2% and -0.3%, respectively. Beam profiles generated with both systems agreed with Monte Carlo measurements and previous literature findings. CONCLUSIONS: TLDs and EBT3 film dosimeters could potentially be used in MR/CT visible tissue equivalent phantoms that will experience a magnetic field environment.

Towards integration of a liquid-filled fiber capillary for supercontinuum generation in the 1.2-2.4 µm range.

We demonstrate supercontinuum generation in unspliced as well as in integrated CS(2)-filled capillary fibers at different pump wavelengths of 1030 nm, 1510 nm, and 1685 nm. A novel method for splicing a liquid-filled capillary fiber to a standard single-mode optical fiber is presented. This method is based on mechanical splicing using a direct-laser written polymer ferrule using a femtosecond two-photon polymerization process. We maintain mostly single-mode operation despite the multi-mode capability of the liquid-filled capillaries. The generated supercontinua exhibit a spectral width of over 1200 nm and 1000 nm for core diameters of 5 µm and 10 µm, respectively. This is an increase of more than 50 percent compared to previously reported values in the literature due to improved dispersion properties of the capillaries.

Mid-infrared Fourier-transform spectroscopy with a high-brilliance tunable laser source: investigating sample areas down to 5 µm diameter.

We demonstrate highly sensitive infrared spectroscopy of sample volumes close to the diffraction limit by coupling a femtosecond fiber-feedback optical parametric oscillator (OPO) to a conventional Fourier-transform infrared (FTIR) spectrometer. The high brilliance and long-term stable infrared radiation with 1e(2)-bandwidths up to 125 nm is easily tunable between 1.4 µm and 4.2 µm at 43 MHz repetition rate and thus enables rapid and low-noise infrared spectroscopy. We demonstrate this by measuring typical molecular vibrations in the range of 3 µm. Combined with surface-enhanced infrared spectroscopy, where the confined electromagnetic near-fields of resonantly excited metal nanoparticles are employed to enhance molecular vibrations, we realize the spectroscopic detection of a molecular monolayer of octadecanethiol. In comparison to conventional light sources and synchrotron radiation, our compact table-top OPO system features a significantly improved performance making it highly suitable for rapid analysis of minute amounts of molecular species in life science and medicine laboratories.

High-power femtosecond mid-infrared optical parametric oscillator at 7 µm based on CdSiP(2).

We report a femtosecond optical parametric oscillator (OPO) for the mid-infrared (mid-IR), generating a record average power of 110 mW at 7 µm. The OPO, based on CdSiP(2) (CSP) as the nonlinear crystal, provides idler wavelength tuning across 6540-7186 nm with spectral bandwidths >400 nm at -10 dB level over the entire range, and a maximum bandwidth of 478 nm at 6.9 µm. To the best of our knowledge, this is the highest average power generated from a femtosecond OPO in the deep mid-IR. The OPO also provides near-IR signal wavelengths tunable across 1204-1212 nm with a usable power of 450 mW in 418-fs pulses at 1207 nm. The simultaneously measured signal and idler power exhibit a passive stability better than 1.6% rms and 3% rms, respectively. A mid-IR idler spectral stability with a standard deviation of the frequency fluctuations better than 40 MHz over 15 min, limited by the measurement resolution, is realized. Using the mid-IR idler from the CSP OPO, we perform Fourier-transform spectroscopy to detect liquid phase organic solvent, toluene (C(7)H(8)), in the molecular fingerprint region.

[Characteristics of 200 patients with suspected implant allergy compared to 100 symptom-free arthroplasty patients]. / Charakteristika von 200 Patienten mit Verdacht auf Implantatallergie im Vergleich zu 100 beschwerdefreien Endoprothesenträgern.

BACKGROUND: Data on implant allergies are incomplete; therefore, we compared the data on allergy history, patch test (PT) and lymphocyte transformation test (LTT) results in a patient series from the Munich implant allergy outpatient department with symptom-free arthroplasty patients. PATIENTS AND METHODS: In this study 200 arthroplasty patients with complaints involving the prosthesis (130 female, 187 knee and 13 hip prostheses) and in parallel 100 symptom-free patients (75 female, 47 knee and 53 hip prostheses) were investigated. A questionnaire-aided history including implant type, cementing, intolerance of dental materials, atopy, cutaneous metal intolerance (CMI) and PT, including a standard series with Ni, Co, Cr, seven bone cement components, including gentamicin and benzoyl peroxide and LTT for Ni, Co and Cr. RESULTS: In the knee arthroplasty patients with complaints 9.1% showed dental material intolerance, 23.5% atopy, 25.7% CMI, 18.2% metal allergies, 7.4% gentamicin allergy and 27.8% positive metal LTT (mostly to Ni). In symptom-free patients 0% showed dental material intolerance, 19.1% atopy, 12.8% CMI, 12.8% metal allergy, 0% gentamicin allergy and 17% positive metal LTT. CONCLUSIONS: Characteristics of the patients with complaints were increased intolerance of dental materials, higher rates of atopy, CMI, metal and gentamicin allergy and LTT reactivity.

[Knowledge about UV-radiation and sun protection: survey of adolescents and young adults in Bavaria]. / Kenntnisstand zum Thema UV-Strahlung und Sonnenschutz : Befragung von bayerischen Jugendlichen und jungen Erwachsenen.

BACKGROUND: Identifying deficits in sun protection knowledge and behavior can serve as a starting point for primary prevention interventions. The aim of this study was to investigate knowledge and behavior related to ultraviolet radiation in the population between 14 and 45 years of age in Bavaria, as well as effects of the awareness campaign "Sensible in the Sun". METHODS: In two Bavarian districts, 545 individuals of the target population completed a telephone survey about risks of UV-radiation, sun protection knowledge and behavior, and effects of the campaign. RESULTS: Sunburn and skin cancer as adverse effects of ultraviolet radiation were named by almost every participant. When asked about protective interventions, 91% mentioned sunscreen and 45-54% clothing, limited stay in the sun and seeking shade at noon. Women were better informed than men, adults better than adolescents. 10.6% were aware of the campaign. In this group, 37.9% had been motivated to consider their sun protective behavior; 13.8% (especially women >30 years) stated they had changed their behavior because of the campaign. CONCLUSION: There were deficits in knowledge, especially about eye damage and the importance of getting slowly used to UV radiation. Physician advice, but also broadcast and print media, has an effect on UV-related knowledge.

[Prevention and early detection of cancer of the skin]. / Prävention und Früherkennung von Hautkrebs.

The article demonstrates the importance of prevention and early detection of skin cancer as a consequence of the increasing morbidity and mortality of these tumours. Epidemiology, clinical appearance, diagnosis and therapy of the three most important and also most frequent malignant tumours of the skin, i.e. malignant melanoma, squamous cell carcinoma and basal cell carcinoma, are summarised. Subsequently the resulting means for primary and secondary prevention of these tumours are discussed. Finally the possibilities of the public health service for the prevention and early detection of skin cancer in Germany are shown with emphasis on the Bavarian prevention campaign "Sonne(n) mit Verstand" ("Sun with Sense").

Treatment of disseminated ocular melanoma with sequential fotemustine, interferon alpha, and interleukin 2.

Malignant melanoma of the uvea is remarkable for purely haematogenous dissemination and its tendency to metastasise to the liver. Although the liver is involved in up to 95% of patients, 50% of these also develop extrahepatic metastases, most often in the lungs, bone, skin, and brain. The only effective treatments reported to date relied on hepatic arterial chemoembolisation or -perfusion. The objective of this study was to establish a therapy protocol addressing patients with both sole liver involvement and systemic disease. Forty-eight patients with metastatic ocular melanoma received fotemustine 100 mg m(-2) either as 60-min infusion into the hepatic artery or as 15-min infusion via a peripheral vein, depending on the metastatic sites involved, i.e., restriction to the liver or hepatic together with extrahepatic disease. For the first treatment cycle this infusion was repeated after one week. For all cycles, subsequent to a three week resting period, patients received an immunotherapy consisting of subcutaneous interleukin 2 and interferon alpha(2). Although objective responses were more frequent within the cohort receiving intraarterial fotemustine (21.7 vs 8%), this difference did not translate into a significant benefit in overall survival, i.e., 369 and 349 days, respectively. Of note, this overall survival is much longer than that repeatedly reported for stage IV uveal melanoma not treated with fotemustine, suggesting a therapeutic activity of this cytostatic drug even after systemic administration.

[Palpable migratory acriform erythema and lymphocytic infiltration of the skin--different presentations of the same entity?]. / Erythema migrans arciforme et palpabile und Lymphocytic Infiltration of the Skin--unterschiedliche Erscheinungsformen derselben Entität?

Palpable arciform migratory erythema of Clark (PAME) has been described as a rare member in the group of T-cell pseudolymphoma. The clinical picture of infiltrated annular erythema developing into large migrating lesions with the trunk as predilection site is distinctive from other pseudolymphomas. Because of the very similar histology and immunohistochemistry in comparison to the more frequent lymphocytic infiltration of the skin of Jessner and Kanof (LIS) doubts have been raised about the existence of PAME as an unique entity. A 46-year old patient presented with the typical picture of PAME on his trunk while showing typical lesions of LIS on his neck and face. Both diseases showed synchronous intermittent remissions in response to different therapeutic modalities. Multiple biopsies were subsequently performed and histological, immunohistochemical and molecular biological examinations did not reveal relevant differences between PAME and LIS in this patient. We conclude that the findings in this key case suggest that the T-cell pseudolymphoma PAME is not an unique entity, but a special clinical presentation of LIS.

A novel methotrexate-albumin (mtx-rsa)-conjugate causes significant growth delay of o-342 ovarian-carcinoma in-vivo.

The increased uptake of native serum albumin in tumors is well described. In previous approaches to use this distribution pattern for tumor therapy, albumin molecules were loaded with maximum quantities of antineoplastic drugs. To preserve the properties of native albumin and to avoid enhanced phagocytotic clearance, we used methotrexate (MTX)-albumin-conjugates with a molar loading ratio of 1:1. In this study we evaluated the effects of single injections of MTX-rat-serum albumin (MTX-RSA) containing 50, 20 and 10 mug MTX on 40 BDIX rats bearing O-342 ovarian carcinoma. Tumor volume post treatment and area-under-the-curve of tumor volumes over treatment were compared with an untreated group using the Mann-Whitney U-test. MTX-RSA treatment caused dose dependent effects and in the 50 mug MTX-dosage significant (P 0.01) growth delay. Additional distribution studies with indirectly radio-iodinated MTX-RSA confirmed the prominent tumor uptake of this compound. We conclude that MTX-albumin-conjugates created with optimized labeling techniques and loading ratios cause significant effects even with very low MTX-doses. Thus these compounds may contribute to enhance the efficacy of MTX-treatment.