Supine MRI for regional breast radiotherapy: Imaging axillary lymph nodes before and after sentinel-node biopsy

Regional radiotherapy (RT) is increasingly used in breast cancer treatment. Conventionally, computed tomography (CT) is performed for RT planning. Lymph node (LN) target levels are delineated according to anatomical boundaries. Magnetic resonance imaging (MRI) could enable individual LN delineation. The purpose was to evaluate the applicability of MRI for LN detection in supine treatment position, before and after sentinel-node biopsy (SNB). Twenty-three female breast cancer patients (cTis-3N0M0) underwent 1.5 T MRI, before and after SNB, in addition to CT. Endurance for MRI was monitored. Axillary levels were delineated. LNs were identified and delineated on MRI from before and after SNB, and on CT, and compared by Wilcoxon signed-rank tests. LN locations and LN-based volumes were related to axillary delineations and associated volumes. Although postoperative effects were visible, LN numbers on postoperative MRI (median 26 LNs) were highly reproducible compared to preoperative MRI when adding excised sentinel nodes, and higher than on CT (median 11, p < 0.001). LN-based volumes were considerably smaller than respective axillary levels. Supine MRI of LNs is feasible and reproducible before and after SNB. This may lead to more accurate RT target definition compared to CT, with potentially lower toxicity. With the MRI techniques described here, initiation of novel MRI-guided RT strategies aiming at individual LNs could be possible

ADC measurements on the Unity MR-linac - A recommendation on behalf of the Elekta Unity MR-linac consortium

Background and purpose: Diffusion-weighted imaging (DWI) for treatment response monitoring is feasibleon hybrid magnetic resonance linear accelerator (MR-linac) systems. The MRI scanner of the ElektaUnity system has an adjusted design compared to diagnostic scanners. We investigated its impact onmeasuring the DWI-derived apparent diffusion coefficient (ADC) regarding three aspects: the choice ofb-values, the spatial variation of the ADC, and scanning during radiation treatment. The aim of this studyis to give recommendations for accurate ADC measurements on Unity systems.Materials and methods: Signal-to-noise ratio (SNR) measurements with increasing b-values were done todetermine the highest bvalue that can be measured reliably. The spatial variation of the ADC wasassessed on six Unity systems with a cylindrical phantom of 40 cm diameter. The influence of gantry rotationand irradiation was investigated by acquiring DWI images before and during treatment of 11 prostatecancer patients.Results: On the Unity system, a maximum b-value of 500 s/mm2 should be used for ADC quantification, asa trade-off between SNR and diffusion weighting. Accurate ADC values were obtained within 7 cm fromthe iso-center, while outside this region ADC values deviated more than 5%. The ADC was not influencedby the rotating linac or irradiation during treatment.Conclusion: We provide Unity system specific recommendations for measuring the ADC. This willincrease the consistency of ADC values acquired in different centers on the Unity system, enabling largecohort studies for biomarker discovery and treatment response monitoring.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Radiation tolerance of the rat spinal cord: volume effects and MR imaging.

Contains fulltext : 70981.pdf (publisher's version ) (Open Access)RU Radboud Universiteit Nijmegen, 10 juni 2008Promotores : Kogel, A.J. van der, Heerschap, A. Co-promotores : Visser, A.G., Pop, L.A.M.169 p

Dose-volume effects in rat thoracolumbar spinal cord: the effects of nonuniform dose distribution.

Item does not contain fulltextPURPOSE: To investigate dose-volume effects in rat spinal cord irradiated with nonuniform dose distributions and to assess regional differences in radiosensitivity. METHODS AND MATERIALS: A total of 106 rats divided into three groups were irradiated with (192)Ir gamma-rays at a high dose rate. The groups were irradiated with one, two, or six catheters distributed around the thoracolumbar spinal cord to create different dose distributions. After irradiation, the animals were tested for motor function for 9 months. The response was defined as motor dysfunction and WM or nerve root necrosis. Dose-response data were analyzed with a probit analysis as function of the dose level at a percentage of the volume (D(%)) and with different normal tissue complication probability models. Additionally, the histologic responses of the individual dose voxels were analyzed after registration with the histologic sections. RESULTS: The probit analysis at D(24) (24% of the volume) gave the best fit results. In addition, the Lyman Kutcher Burman model and the relative seriality model showed acceptable fits, with volume parameters of 0.17 and 0.53, respectively. The histology-based analysis revealed a lower radiosensitivity for the dorsal (50% isoeffective dose [ED(50)] = 32.3) and lateral WM (ED(50) = 33.7 Gy) compared with the dorsal (ED(50) = 25.9 Gy) and ventral nerve roots (ED(50) = 24.1 Gy). CONCLUSIONS: For this nonuniform irradiation, the spinal cord did not show typical serial behavior. No migration terms were needed for an acceptable fit of the dose-response curves. A higher radiosensitivity for the lumbar nerve roots than for the thoracic WM was found

Radiation effects in the rat spinal cord: evaluation with apparent diffusion coefficient versus T2 at serial MR imaging.

Contains fulltext : 81770.pdf (publisher's version ) (Closed access)PURPOSE: To prospectively determine whether apparent diffusion coefficients (ADCs) are more sensitive to radiation-induced changes in the rat spinal cord than T2 relaxation times. MATERIALS AND METHODS: The study was approved by the institutional ethical committee on animal welfare. One centimeter of the thoracolumbar spinal cord of six rats was irradiated with 36 Gy. For 3-6 months after irradiation, five 7.0-T magnetic resonance (MR) imaging measurements were performed in each rat until motor impairment developed. Six age-matched rats were examined as controls. Measurements were performed by using diffusion-weighted imaging with five b values and a spin-echo sequence with 20 echoes. ADC and T2 values were calculated, and the spatiotemporal evolution of the radiation-induced lesions was determined semiautomatically. The final MR measurements were compared with the histologic findings. RESULTS: Shortly before the neurologic signs appeared, the first radiation effects manifested as well-circumscribed white matter (WM) lesions with a low longitudinal ADC and normal or high T2. WM lesions with high T2 correlated with confluent necrosis at histologic analysis, whereas WM lesions with normal T2 correlated with focal necrosis and demyelination. In the gray matter (GM), lesions with diffusely high T2 were present and were attributed to edema. T2 changes in the GM preceded T2 and ADC changes in the WM. CONCLUSION: In the WM, longitudinal ADC was more sensitive for the detection of radiation damage than T2, but in the GM, T2 was more sensitive

Parp1-XRCC1 and the repair of DNA double strand breaks in mouse round spermatids.

Contains fulltext : 89842.pdf (publisher's version ) (Closed access)The repair of DNA double strand breaks (DSBs) in male germ cells is slower and differently regulated compared to that in somatic cells. Round spermatids show DSB repair and are radioresistant to apoptosis induction. Mutation induction studies using ionizing irradiation, indicated a high frequency of chromosome aberrations (CA) in the next generation. Since they are in a G1 comparable stage of the cell cycle, haploid spermatids are expected to repair DSBs by the non-homologous end-joining pathway (NHEJ). However, immunohistochemical evidence indicates that not all components of the classical NHEJ pathway are available since the presence of DNA-PKcs cannot be shown. Here, we demonstrate that round spermatids, as well as most other types of male germ cells express both Parp1 and XRCC1. Therefore, we have determined whether the alternative Parp1/XRCC1 dependent NHEJ pathway is active in these nuclei and also have tested for classical NHEJ activity by a genetic method. To evaluate DSB repair in SCID mice, deficient for DNA-PKcs, and to study the involvement of the Parp1/XRCC1 dependent NHEJ pathway in round spermatids, the loss of gamma-H2AX foci after irradiation has been determined in nucleus spreads of round spermatids of SCID mice and in nucleus spreads and histological sections of Parp1-inhibited mice and their respective controls. Results show that around half of the breaks in randomly selected round spermatids are repaired between 1 and 8h after irradiation. The repair of 16% of the induced DSBs requires DNA-PKcs and 21% Parp1. Foci numbers in the Parp1-inhibited testes tend to be higher in spermatids of all epithelial stages reaching significance in stages I-III which indicates an active Parp1/XRCC1 pathway in round spermatids and a decreased repair capacity in later round spermatid stages. In Parp1-inhibited SCID mice only 14.5% of the breaks were repaired 8h after irradiation indicating additivity of the two NHEJ pathways in round spermatids