Multi-institutional feasibility study of a fast patient localization method in total marrow irradiation with helical tomotherapy: a global health initiative by the international consortium of total marrow irradiation.

PURPOSE: To develop, characterize, and implement a fast patient localization method for total marrow irradiation. METHODS AND MATERIALS: Topographic images were acquired using megavoltage computed tomography (MVCT) detector data by delivering static orthogonal beams while the couch traversed through the gantry. Geometric and detector response corrections were performed to generate a megavoltage topogram (MVtopo). We also generated kilovoltage topograms (kVtopo) from the projection data of 3-dimensional CT images to reproduce the same geometry as helical tomotherapy. The MVtopo imaging dose and the optimal image acquisition parameters were investigated. A multi-institutional phantom study was performed to verify the image registration uncertainty. Forty-five MVtopo images were acquired and analyzed with in-house image registration software. RESULTS: The smallest jaw size (front and backup jaws of 0) provided the best image contrast and longitudinal resolution. Couch velocity did not affect the image quality or geometric accuracy. The MVtopo dose was less than the MVCT dose. The image registration uncertainty from the multi-institutional study was within 2.8 mm. In patient localization, the differences in calculated couch shift between the registration with MVtopo-kVtopo and MVCT-kVCT images in lateral, cranial-caudal, and vertical directions were 2.2 ± 1.7 mm, 2.6 ± 1.4 mm, and 2.7 ± 1.1 mm, respectively. The imaging time in MVtopo acquisition at the couch speed of 3 cm/s was <1 minute, compared with ≥15 minutes in MVCT for all patients. CONCLUSION: Whole-body MVtopo imaging could be an effective alternative to time-consuming MVCT for total marrow irradiation patient localization.

Anatomic segmentation improves prostate cancer detection with artificial neural networks analysis of 1H magnetic resonance spectroscopic imaging.

PURPOSE: To assess whether an artificial neural network (ANN) model is a useful tool for automatic detection of cancerous voxels in the prostate from (1)H-MRSI datasets and whether the addition of information about anatomical segmentation improves the detection of cancer. MATERIALS AND METHODS: The Institutional Review Board approved this HIPAA-compliant study and waived informed consent. Eighteen men with prostate cancer (median age, 55 years; range, 36-71 years) who underwent endorectal MRI/MRSI before radical prostatectomy were included in this study. These patients had at least one cancer area on whole-mount histopathological map and at least one matching MRSI voxel suspicious for cancer detected. Two ANN models for automatic classification of MRSI voxels in the prostate were implemented and compared: model 1, which used only spectra as input, and model 2, which used the spectra plus information from anatomical segmentation. The models were trained, tested and validated using spectra from voxels that the spectroscopist had designated as cancer and that were verified on histopathological maps. RESULTS: At ROC analysis, model 2 (AUC = 0.968) provided significantly better (P = 0.03) classification of cancerous voxels than did model 1 (AUC = 0.949). CONCLUSION: Automatic analysis of prostate MRSI to detect cancer using ANN model is feasible. Application of anatomical segmentation from MRI as an additional input to ANN improves the accuracy of detecting cancerous voxels from MRSI.

High resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of surviving C6 glioma cells after X-ray irradiation.

PURPOSE: To study biochemical response of living model of glioma to X-rays irradiation using high resolution proton nuclear magnetic resonance (1H NMR) spectroscopy. MATERIAL AND METHODS: Rat glioma C6 cells were irradiated with 3.8 Gy (D0, the 37% clonogenic survival dose) of X-rays from a teletherapy unit at the dose rate 8.8 Gy/min. After irradiation the cells were incubated at 37°C/5%CO2/95%O2 for various period of incubation (24, 48, 72 and 96 hours) in the fresh medium. The high resolution 1H NMR spectra of the agarose-cell mixtures (2 x 10(7) cells/ml) were acquired using a Varian Inova-300 multinuclear pulsed NMR spectrometer operating at the 1H resonance frequency of 300 MHz. The mean spectra were obtained as the averages of six independent measurements. RESULTS: The statistically significant increase in the CH2/CH3 lipid signals ratio in the C6 cells after irradiation with 3.8 Gy dose and incubation for 24-96 h was observed. CONCLUSIONS: Our method of the sample preparation enables the metabolic effects of irradiation to be observed in viable cells, which can effectively support the identification of the spectroscopic changes in vivo. Application of the gel suspensions in the NMR studies has advantages over the usual liquid suspensions in terms of improved reproducibility of the data and cell viability, with no net loss of the spectral quality.

Magnetic resonance spectroscopic evaluation of brain tissue metabolism after irradiation for pediatric brain tumors in long-term survivors: a report of two cases.

OBJECTIVE: The aim of our study was to evaluate the metabolic profile of brain tissue of two long-term survivors of childhood brain tumors. MATERIALS: Two males who were 25 and 33 years old at the time of examination and had been irradiated for brain tumors at the age of 17 and 13 years respectively. The first subject had been operated on radically for medulloblastoma and received craniospinal axis irradiation composed of a whole brain radiotherapy with boost to the posterior fossa (total dose (TD) = 59.4 Gy in 33 fractions) and spinal canal irradiation (TD = 30 Gy in 20 fractions) according to the protocol at the time of treatment. The second subject had previously received whole brain irradiation (TD = 45 Gy in 19 fractions) because of inoperable central region tumor of unknown histology. METHODS: Short echo-time (TE = 30 ms) point-resolved spectra were obtained using a 2 T magnet. Ratios of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), lactate (Lac) and lipids (Lip) signal intensities were calculated using the creatine (Cr) signal as an internal reference. The spectra were acquired both from the tumor bed area and uninvolved brain tissue in the first subject, and from uninvolved brain areas of frontal and occipital lobes in the second subject. RESULTS: In both cases, MRS examination revealed ratios of NAA/Cr, Cho/Cr and mI/Cr within normal range in most spectra. Nevertheless, a slight elevation of Lac/Cr (2.47 and 1.05) and a more pronounced elevation of Lip/Cr proportions (45.77 and 3.97 respectively, in uninvolved sites) were detected in both patients. CONCLUSIONS: Metabolic parameters correlated with neuronal function (NAA/Cr) and cell membrane metabolites turnover (Cho/Cr) seem to recover to normal values in long-term survivors of brain tumors. Lac/Cr and Lip/Cr proportions could be considered parameters indicating permanent radiation-induced brain damage; however, this proposal requires further investigation.

Long-term normal-appearing brain tissue monitoring after irradiation using proton magnetic resonance spectroscopy in vivo: statistical analysis of a large group of patients.

PURPOSE: The aim of this study was to detect the non-neoplastic white-matter changes vs. time after irradiation using 1H nuclear magnetic resonance (NMR) spectroscopy in vivo. METHODS AND MATERIALS: A total of 394 1H MR spectra were acquired from 100 patients (age 19-74 years; mean and median age, 43 years) before and during 2 years after radiation therapy (the mean absorbed doses calculated for the averaged spectroscopy voxels are similar and close to 20 Gy). RESULTS: Oscillations were observed in choline-containing compounds (Cho)/creatine and phosphocreatine (Cr), Cho/N-acetylaspartate (NAA), and center of gravity (CG) of the lipid band in the range of 0.7-1.5 ppm changes over time reveal oscillations. The parameters have the same 8-month cycle period; however the CG changes precede the other by 2 months. CONCLUSIONS: The results indicate the oscillative nature of the brain response to irradiation, which may be caused by the blood-brain barrier disruption and repair processes. These oscillations may influence the NMR results, depending on the cycle phase in which the NMR measurements are performed in. The earliest manifestation of radiation injury detected by magnetic resonance spectroscopy is the CG shift.

Could lipid CH2/CH3 analysis by in vivo 1H MRS help in differentiation of tumor recurrence and post-radiation effects?

PURPOSE: To inspect the potential diagnostic role of in vivo 1H MRS lipid methylene CH2 to methyl CH3 signal ratio in differentiation of recurrent brain tumor from radiation injury. METHODS: Two patients--one with documented recurrence and the other without recurrence--were monitored by means of 1H MRS before and during two years after radiation therapy. The comparative group consisted of 20 patients with glial tumor recurrence diagnosed 2 years after the radiotherapy. RESULTS: In case of tumor recurrence, an increase of the lipid CH2/CH3 value is observed. In contrast, for the patient with no tumor recurrence and within the brain areas distant from the tumor the CH2/CH3 ratio reveals a negative correlation vs. time after irradiation. The Lip trend to increase on radiotherapy both at the tumor bed and within the non-involved areas lessens the value of Lip as a marker of tumor recurrence. CONCLUSION: The analysis of the lipid CH2/CH3 ratio may be useful in differentiation of the tumor recurrence from radiation response. The Lip signals observed in normally appearing brain tissue after radiotherapy could originate from the change of metabolism of irradiated cells.

Multiple bystander effect of irradiated megacolonies of melanoma cells on non-irradiated neighbours.

The multicellular megacolonies of human melanoma Me45 line growing on one part of the bottom of culture flasks were irradiated with 5 Gy (60Co), whereas megacolonies growing on the second part of the bottom were shielded. The bystander effect of radiation-traversed cells on non-traversed cells was studied during postradiation co-cultivation. Activity of superoxide dismutase (Mn and CuZn subunits), glutathione peroxidase (GSH-Pox) and malondialdehyde (MDA) concentration as a biochemical markers of bystander effect were monitored for a period of 72 h. The DNA damage was measured by the comet assay. Micronucleus induction, mitotic index and cellular death as apoptosis or necrosis were simultaneously estimated, based on morphologic criteria. The bystander effect of irradiated cells on their neighbours was observed as a slight increase of MDA concentration, comparable decrease of GSH-Pox activity, and some fluctuation of mitochondrial and cytoplasmic isoenzymes of SOD. DNA strand breaks and rejoining measured by comet assay as mean tail length, demonstrated clearly the bystander effect for nontraversed radiation cells, additionally verified by tail moment. There was also a significant increase of micronucleation and apoptosis generated by radiation traversed cells in shielded neighbours. Furthermore, significantly higher increase of necrosis in shielded neighbour cells compared to radiation traversed cells was observed. Proliferative activity showed a suppression in both, radiation traversed and shielded neighbour cells in all measured time points. The behaviour of used parameters points to the radical nature of modificators secreted by radiation traversed cells inducing bystander toxic damage in shielded neighbour cells.