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Highlights • MRI-only IGRT accuracy is ≤2 mm as compared to CT but significant differences were observed. • MRI-only CBCT-based IGRT seems feasible but caution is advised. • The median absolute error (MeAE) for independent verification on the sCT quality is proposed. • A MeAE around 0.1 in mass density could call for sCT quality inspection., Background and purpose Radiotherapy (RT) based on magentic resonance imaging (MRI) only is currently used clinically in the pelvis. A synthetic computed tomography (sCT) is needed for dose planning. Here, we investigate the accuracy of cone beam CT (CBCT) based MRI-only image guided RT (IGRT) and sCT image quality. Materials and methods CT, MRI and CBCT scans of ten prostate cancer patients were included. The MRI was converted to a sCT using a multi-atlas approach. The sCT, CT and MR images were auto-matched with the CBCT on the bony anatomy. Paired sCT-CT and sCT-CBCT data were created. CT numbers were converted to relative electron (RED) and mass densities (DES) using a standard calibration curve for the CT and sCT. For the CBCT RED/DES conversion, a phantom and paired CT-CBCT population based calibration curve was used. For the latter, the CBCT numbers were averaged in 100 HU bins and the known RED/DES of the CT were assigned. The paired sCT-CT and sCT-CBCT data were averaged in bins of 10 HU or 0.01 RED/DES. The median absolute error (MeAE) between the sCT-CT and sCT-CBCT bins was calculated. Wilcoxon rank-sum tests were carried out for the IGRT and MeAE study. Results The mean sCT or MR IGRT difference from CT was ≤ 2 mm but significant differences were observed. A CBCT HU or phantom-based RED/DES MeAE did not estimate the sCT quality similar to a CT based MeAE but the CBCT population-based RED/DES MeAE did. Conclusions MRI-only CBCT-based IGRT seems feasible but caution is advised. A MeAE around 0.1 DES could call for sCT quality inspection.

Purpose: We investigated the impact on computed tomography (CT) image quality and photon, electron, and proton head-and-neck (H&N) radiotherapy (RT) dose calculations of three CT metal artifact reduction (MAR) approaches: A CT-based algorithm (oMAR Philips Healthcare), manual water override, and our recently presented, Magnetic Resonance (MR)-based kerMAR algorithm. We considered the following three hypotheses: I: Manual water override improves MAR over the CT- and MR-based alternatives; II: The automatic algorithms (oMAR and kerMAR) improve MAR over the uncorrected CT; III: kerMAR improves MAR over oMAR. Methods: We included a veal shank phantom with/without six metal inserts and nine H&N RT patients with dental implants. We quantified the MAR capabilities by the reduction of outliers in the CT value distribution in regions of interest, and the change in particle range and photon depth at maximum dose. Results: Water override provided apparent image improvements in the soft tissue region but insignificantly or negatively influenced the dose calculations. We however found significant improvements in image quality and particle range impact, compared to the uncorrected CT, when using oMAR and kerMAR. kerMAR in turn provided superior improvements in terms of high intensity streak suppression compared to oMAR, again with associated impacts on the particle range estimates. Conclusion: We found no benefits of the water override compared to the rest, and tentatively reject hypothesis I. We however found improvements in the automatic algorithms, and thus support for hypothesis II, and found the MR-based kerMAR to improve upon oMAR, supporting hypothesis III.

Metal implants give rise to metal artifacts in computed tomography (CT) images, which may lead to diagnostic errors and erroneous CT number estimates when the CT is used for radiation therapy planning. Methods for reducing metal artifacts by exploiting the anatomical information provided by coregistered magnetic resonance (MR) images are of great potential value, but remain technically challenging due to the poor contrast between bone and air on the MR image. In this paper, we present a novel MR-based algorithm for automatic CT metal artifact reduction (MAR), referred to as kerMAR. It combines kernel regression on known CT value/MR patch pairs in the uncorrupted patient volume with a forward model of the artifact corrupted values to estimate CT replacement values. In contrast to pseudo-CT generation that builds on multi-patient modelling, the algorithm requires no MR intensity normalisation or atlas registration. Image results for 7 head-and-neck radiation therapy patients with T1-weighted images acquired in the same fixation as the RT planning CT suggest a potential for more complete MAR close to the metal implants than the oMAR algorithm (Philips) used clinically. Our results further show improved performance in air and bone regions as compared to other MR-based MAR algorithms. In addition, we experimented with using kerMAR to define a prior for iterative reconstruction with the maximum likelihood transmission reconstruction algorithm, however with no apparent improvements.

Purpose: In radiotherapy (RT) based on magnetic resonance imaging (MRI) as the only modality, the information on electron density must be derived from the MRI scan by creating a so-called pseudo computed tomography (pCT). This is a nontrivial task, since the voxel-intensities in an MRI scan are not uniquely related to electron density. To solve the task, voxel-based or atlas-based models have typically been used. The voxel-based models require a specialized dual ultrashort echo time MRI sequence for bone visualization and the atlas-based models require deformable registrations of conventional MRI scans. In this study, we investigate the potential of a patch-based method for creating a pCT based on conventional T 1-weighted MRI scans without using deformable registrations. We compare this method against two state-of-the-art methods within the voxel-based and atlas-based categories. Methods: The data consisted of CT and MRI scans of five cranial RT patients. To compare the performance of the different methods, a nested cross validation was done to find optimal model parameters for all the methods. Voxel-wise and geometric evaluations of the pCTs were done. Furthermore, a radiologic evaluation based on water equivalent path lengths was carried out, comparing the upper hemisphere of the head in the pCT and the real CT. Finally, the dosimetric accuracy was tested and compared for a photon treatment plan. Results: The pCTs produced with the patch-based method had the best voxel-wise, geometric, and radiologic agreement with the real CT, closely followed by the atlas-based method. In terms of the dosimetric accuracy, the patch-based method had average deviations of less than 0.5% in measures related to target coverage. Conclusions: We showed that a patch-based method could generate an accurate pCT based on conventional T 1-weighted MRI sequences and without deformable registrations. In our evaluations, the method performed better than existing voxel-based and atlas-based methods and showed a promising potential for RT of the brain based only on MRI.

Radiotherapy based on magnetic resonance imaging as the sole modality (MRI-only RT) is an area of growing scientific interest due to the increasing use of MRI for both target and normal tissue delineation and the development of MR based delivery systems. One major issue in MRI-only RT is the assignment of electron densities (ED) to MRI scans for dose calculation and a similar need for attenuation correction can be found for hybrid PET/MR systems. The ED assigned MRI scan is here named a substitute CT (sCT). In this review, we report on a collection of typical performance values for a number of main approaches encountered in the literature for sCT generation as compared to CT. A literature search in the Scopus database resulted in 254 papers which were included in this investigation. A final number of 50 contributions which fulfilled all inclusion criteria were categorized according to applied method, MRI sequence/contrast involved, number of subjects included and anatomical site investigated. The latter included brain, torso, prostate and phantoms. The contributions geometric and/or dosimetric performance metrics were also noted. The majority of studies are carried out on the brain for 5-10 patients with PET/MR applications in mind using a voxel based method. T1 weighted images are most commonly applied. The overall dosimetric agreement is in the order of 0.3-2.5%. A strict gamma criterion of 1% and 1mm has a range of passing rates from 68 to 94% while less strict criteria show pass rates > 98%. The mean absolute error (MAE) is between 80 and 200 HU for the brain and around 40 HU for the prostate. The Dice score for bone is between 0.5 and 0.95. The specificity and sensitivity is reported in the upper 80s% for both quantities and correctly classified voxels average around 84%. The review shows that a variety of promising approaches exist that seem clinical acceptable even with standard clinical MRI sequences. A consistent reference frame for method benchmarking is probably necessary to move the field further towards a widespread clinical implementation.

Radiotherapy (RT) based on magnetic resonance imaging (MRI) as the only modality, so-called MRI-only RT, would remove the systematic registration error between MR and computed tomography (CT), and provide co-registered MRI for assessment of treatment response and adaptive RT. Electron densities, however, need to be assigned to the MRI images for dose calculation and patient setup based on digitally reconstructed radiographs (DRRs). Here, we investigate the geometric and dosimetric performance for a number of popular voxel-based methods to generate a so-called pseudo CT (pCT). Five patients receiving cranial irradiation, each containing a co-registered MRI and CT scan, were included. An ultra short echo time MRI sequence for bone visualization was used. Six methods were investigated for three popular types of voxel-based approaches; (1) threshold-based segmentation, (2) Bayesian segmentation and (3) statistical regression. Each approach contained two methods. Approach 1 used bulk density assignment of MRI voxels into air, soft tissue and bone based on logical masks and the transverse relaxation time T2 of the bone. Approach 2 used similar bulk density assignments with Bayesian statistics including or excluding additional spatial information. Approach 3 used a statistical regression correlating MRI voxels with their corresponding CT voxels. A similar photon and proton treatment plan was generated for a target positioned between the nasal cavity and the brainstem for all patients. The CT agreement with the pCT of each method was quantified and compared with the other methods geometrically and dosimetrically using both a number of reported metrics and introducing some novel metrics. The best geometrical agreement with CT was obtained with the statistical regression methods which performed significantly better than the threshold and Bayesian segmentation methods (excluding spatial information). All methods agreed significantly better with CT than a reference water MRI comparison. The mean dosimetric deviation for photons and protons compared to the CT was about 2% and highest in the gradient dose region of the brainstem. Both the threshold based method and the statistical regression methods showed the highest dosimetrical agreement.Generation of pCTs using statistical regression seems to be the most promising candidate for MRI-only RT of the brain. Further, the total amount of different tissues needs to be taken into account for dosimetric considerations regardless of their correct geometrical position.

In radiotherapy treatment planning that is only based on magnetic resonance imaging (MRI), the electron density information usually obtained from computed tomography (CT) must be derived from the MRI by synthesizing a so-called pseudo CT (pCT). This is a non-trivial task since MRI intensities are neither uniquely nor quantitatively related to electron density. Typical approaches involve either a classification or regression model requiring specialized MRI sequences to solve intensity ambiguities, or an atlas-based model necessitating multiple registrations between atlases and subject scans. In this work, we explore a machine learning approach for creating a pCT of the pelvic region from conventional MRI sequences without using atlases. We use a random forest provided with information about local texture, edges and spatial features derived from the MRI. This helps to solve intensity ambiguities. Furthermore, we use the concept of auto-context by sequentially training a number of classification forests to create and improve context features, which are finally used to train a regression forest for pCT prediction. We evaluate the pCT quality in terms of the voxel-wise error and the radiologic accuracy as measured by water-equivalent path lengths. We compare the performance of our method against two baseline pCT strategies, which either set all MRI voxels in the subject equal to the CT value of water, or in addition transfer the bone volume from the real CT. We show an improved performance compared to both baseline pCTs suggesting that our method may be useful for MRI-only radiotherapy.

Purpose Dynamic treatment planning algorithms use a dosimetric leaf separation (DLS) parameter to model the multi-leaf collimator (MLC) characteristics. Here, we quantify the dosimetric impact of an incorrect DLS parameter and investigate whether common pretreatment quality assurance (QA) methods can detect this effect. Methods 16 treatment plans with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique for multiple treatment sites were calculated with a correct and incorrect setting of the DLS, corresponding to a MLC gap difference of 0.5 mm. Pretreatment verification QA was performed with a bi-planar diode array phantom and the electronic portal imaging device (EPID). Measurements were compared to the correct and incorrect planned doses using gamma evaluation with both global (G) and local (L) normalization. Correlation, specificity and sensitivity between the dose volume histogram (DVH) points for the planning target volume (PTV) and the gamma passing rates were calculated. Results The change in PTV and organs at risk DVH parameters were 0.4–4.1%. Good correlation (>0.83) between the PTV mean dose deviation and measured gamma passing rates was observed. Optimal gamma settings with 3%L/3 mm (per beam and composite plan) and 3%G/2 mm (composite plan) for the diode array phantom and 2%G/2 mm (composite plan) for the EPID system were found. Global normalization and per beam ROC analysis of the diode array phantom showed an area under the curve Conclusions A DLS error can worsen pretreatment QA using gamma analysis with reasonable credibility for the composite plan. A low detectability was demonstrated for a 3%G/3 mm per beam gamma setting.

The stem signal, composed of fluorescence and Cerenkov light, becomes a significant source of uncertainty in fiber-coupled afterloaded brachytherapy dosimetry when the source dwells near the fiber cable but far from the detector. A stem suppression technique originally developed for scintillators was adapted for on-line in-vivo dosimetry using fiber-coupled carbon doped aluminum oxide (Al 2 O 3 :C). The technique involved a two-channel optical filtration of the radioluminescence (RL) emitted from a pre-irradiated Al 2 O 3 :C crystal with enhanced sensitivity. The system responded linearly in the absorbed dose range 0.05–50 Gy, as needed under high dose rate (HDR) conditions. The dosimeter was irradiated in a water phantom using a 37 GBq 192 Ir source at source-to-crystal distances ranging from 0.5 cm to 6.7 cm. For irradiation conditions that generated a stem component in the range 4%–15% in the unfiltered signal, and up to 5 ± 1% in a single-channel read-out optimized for Al 2 O 3 :C, the adapted stem suppression technique reduced the stem component to −1 ± 3%. The stem suppressed dosimeter response and the 192 Ir source depth dose curve agreed within position uncertainties, and with a 5% maximum deviation, for distances up to 6 cm.

Carbon-doped aluminum oxide (Al2O3:C) crystals attached to 15 m optical fiber cables can be used for online in vivo dosimetry during, for example, remotely afterloaded brachytherapy. Radioluminescence (RL) is generated spontaneously in Al2O3:C during irradiation, and this scintillator-like signal enables real-time monitoring of the dose delivery. Furthermore, the crystal acts as a passive optically stimulated luminescence (OSL) dosimeter, and the accumulated dose for a full treatment can be obtained while the dosimeter is still in the patient by optical stimulation with a low-power laser. The prime objective of this work was to assess the influence of delay between irradiation and optical stimulation on such measurements. A secondary objective was to demonstrate that previously determined RL/OSL temperature coefficients are independent of the delay between irradiation and OSL readout. These coefficients account for changes in RL and OSL signals with changes in temperature during irradiation and stimulation. The work was primarily based on a set of automated laboratory measurements carried out using 50 kV X-rays (0–3 Gy) with delays in the range of 10–3600 s and temperatures in the range of 10–45 °C. The test protocol involved randomization of five experimental parameters (irradiation dose, two temperatures, and two delays). The main finding was that the delay between irradiation and OSL readout has a small (0.5% for a 1 h delay) but significant influence on the OSL-signals, but none on the temperature coefficients.

We investigated the optically stimulated luminescence (OSL) signal from Al 2 O 3 :C irradiated with 10–60 MeV protons to estimate the potential use of this material as a proton dosimeter. After irradiation, OSL decay curves were read out and we used both the initial part and the total area of these curves as response signal. A precondition for optimal proton dosimetry is an LET-independent response and the experimental data showed such an independence at 0.3 Gy for the initial OSL signal. To understand the experimental results, we applied target and track structure theory. Here, the OSL signal is considered to be a result of target activation and the OSL proton signal is calculated from the OSL gamma signal and a radial dose distribution around the proton track. Although several simplifications were made to ease calculations, the classic track structure theory can qualitatively account for all the main features of the experimental data. We estimate a target radius to be between 30 and 150 nm and associate this radius with a charge migration distance in the crystal. The model calculations suggest that the dose and LET-dependency of the OSL signal is a result of an unique mixture of one- and two-hit targets. This implies that the initial OSL signal from Al 2 O 3 :C in general is not LET-independent at 0.3 Gy or lower doses. However, a mixture of the initial and total OSL signal could provide an LET-independent response in a given LET and dose interval.

Over the last years, attention has been given to applications of Al2O3:C in space and medical dosimetry. One such application is in vivo dose verification in radiotherapy of cancer patients and here we investigate the temperature effects on the radioluminescence (RL) and optically stimulated luminescence (OSL) signals in the room-to-body temperature region. We found that the OSL response changes with both irradiation and stimulation temperatures as well as the OSL integration time. We conclude that temperature effects on the OSL response can be removed by integration if the irradiation temperature is not varied. The RL response only depends on the irradiation temperature. We recommend that calibration should be carried out at the same irradiation temperature at which the measurement is performed (i.e. at body temperature for in vivo measurements). The overall change in the integrated OSL and RL signals with irradiation and stimulation temperature covers an interval from - 0.2 % to 0.6% per ∘ C . This indicates the correction factor one must take into account when performing luminescence dosimetry at different temperatures. The same effects were observed regardless of crystal type, test doses and stimulation and detection wavelengths. The reported temperature dependence seems to be a general property of Al2O3:C.

Background. Radiotherapy based on MRI only (MRI-only RT) shows a promising potential for the brain. Much research focuses on creating a pseudo computed tomography (pCT) from MRI for treatment planning while little attention is often paid to the treatment delivery. Here, we investigate if cone beam CT (CBCT) can be used for MRI-only image-guided radiotherapy (IGRT) and for verifying the correctness of the corresponding pCT.Material and methods. Six patients receiving palliative cranial RT were included in the study. Each patient had three-dimensional (3D) T1W MRI, a CBCT and a CT for reference. Further, a pCT was generated using a patch-based approach. MRI, pCT and CT were placed in the same frame of reference, matched to CBCT and the differences noted. Paired pCT-CT and pCT-CBCT data were created in bins of 10 HU and the absolute difference calculated. The data were converted to relative electron densities (RED) using the CT or a CBCT calibration curve. The latter was either based on a CBCT phantom (phan) or a paired CT-CBCT population (pop) of the five other patients.Results. Non-significant (NS) differences in the pooled CT-CBCT, MRI-CBCT and pCT-CBCT transformations were noted. The largest deviations from the CT-CBCT reference were < 1 mm and 1°. The average median absolute error (MeAE) in HU was 184 ± 34 and 299 ± 34 on average for pCT-CT and pCT-CBCT, respectively, and was significantly different (p < 0.01) in each patient. The average MeAE in RED was 0.108 ± 0.025, 0.104 ± 0.011 and 0.099 ± 0.017 for pCT-CT, pCT-CBCT phan (p < 0.01 on 2 patients) and pCT-CBCT pop (NS), respectively.Conclusions. CBCT can be used for patient setup with either MRI or pCT as reference. The correctness of pCT can be verified from CBCT using a population-based calibration curve in the treatment geometry.

A new system for in vivo dosimetry during radiotherapy has been introduced. Luminescence signals from a small crystal of carbon-doped aluminium oxide (Al 2 O 3 :C) are transmitted through an optical fibre cable to an instrument that contains optical filters, a photomultiplier tube and a green (532 nm) laser. The prime output is continuous wave optically stimulated luminescence (CW-OSL) used for the measurement of the integrated dose. We demonstrate a measurement protocol with high reproducibility and improved linearity, which is suitable for clinical dosimetry. A crystal-specific minimum pre-dose is necessary for signal stabilisation. Simple background subtraction only partially removes the residual signal present at long integration times. Instead, the measurement protocol separates the decay curve into three individual components and only the fast and medium components were used.

In 116 diabetic eyes scheduled for vitreous surgery, the visual evoked potential (VEP) after flash stimulation was recorded prior to surgery. Latencies of the flash evoked potentials show a distribution suggestive of a Gaussian curve with an abnormal extension. Dividing the material into two groups based on a latency shorter or longer than 100 milliseconds revealed a highly significant difference in the visual improvement following surgery between patients with a short and patients with a long latency (P less than 0.001). With a latency longer than 100 millisec. most patients showed no visual change after operation, and among the few who did the change, consisted more often in visual reduction than improvement. Additional investigations in the study reveal that it is likely that the prolonged latency of the flash VEP is due to pathology of the retina or visual pathways.

In this investigation of 2,091 eyes the occurrence of retinal detachment in the aphakic eye has been studied. Two groups are compared as to the incidence and type of cataract. Among 187 cases of aphakic retinal detachment in the second group, the relation between type of cataract, type of tear, cataract surgery and reattachment is recorded and the surgical procedure of the detachment discussed. The significant features and the course of the aphakic detachment are outlined and the predisposition to cataractous eye is emphasized.

To determine whether or not the electrophysiological status of the eye can give information as to the result of vitreous surgery, the visual evoked potential to flash stimulation was measured prior to vitreous surgery. Seventy-four eyes were submitted to surgery. Latencies of flash evoked potentials showed a distribution suggestive of a Gaussian curve with an abnormal extension. Dividing the material into 2 groups based on a latency longer or shorter than 100 millisec revealed a highly significant difference in visual improvement after surgery between patients with long latency and patients with short latency (P less than 0.001). With a latency longer than 100 millisec the patient has an almost equal chance of visual improvement or visual reduction by surgery. The frequency of operative complications was twice as high in patients with latency longer than 100 millisec compared to patients with a latency shorter than 100 millisec.

A method for dynamic angiography and quantitative measurement of fluorescence in ocular vessels in an in vitro experiment and in corneo-conjunctival angiography is described.

Based on a period of introduction with the vitrectomy technic the visual acuity results in 143 consecutive cases performed between 1976 and 1980 are related to the anamnestic information, the pre-, per- and post-operative findings. In this introductional period the patients referred had longstanding retinovitreal changes, and, because of lack of prognostic parameters, all patients were offered surgery regardless of the observed pathology. All vitrectomies were carried out with the Kloti macrostripper and diathermy unit, without any additional instrumentation. From the results of these early cases, we have changed our surgical method to a three-port entrance with a separate infusion canula, a separate fiberoptic illumination and an interchange between vitrector, automatic scissors, hook, stilleto, vacuo needle, forceps and intravitreous photocoagulation through a third port. Diabetics should be offered vitrectomy if vitreous haemorrhages last for more than 3 months. Vitrectomy is considered useless or contraindicated in diabetics with lack of light perception or light projection, neovascular glaucoma, extinguished visual evoked potential. Only an improvement in the peripheral vision can be expected in diabetics with macular detachment. In rhegmatogenous detachment cases with intravitreal traction, vitreous operations should be performed only where intraretinal or retroretinal changes do not prevent mobilization or unfolding of the retina. Traumatic vitreoretinal disorders should be operated upon early.

Metal artifact reduction (MAR) algorithms reduce the errors caused by metal implants in x-ray computed tomography (CT) images and are an important part of error management in radiotherapy. A promising MAR approach is to leverage the information in magnetic resonance (MR) images that can be acquired for organ or tumor delineation. This is however complicated by the ambiguous relationship between CT values and conventional-sequence MR intensities as well as potential co-registration issues. In order to address these issues, this paper proposes a self-tuning Bayesian model for MR-based MAR that combines knowledge of the MR image intensities in local spatial neighborhoods with the information in an initial, corrupted CT reconstructed using filtered back projection. We demonstrate the potential of the resulting model in three widely-used MAR scenarios: image inpainting, sinogram inpainting and model-based iterative reconstruction. Compared to conventional alternatives in a retrospective study on nine head-and-neck patients with CT and T1-weighted MR scans, we find improvements in terms of image quality and quantitative CT value accuracy within each scenario. We conclude that the proposed model provides a versatile way to use the anatomical information in a co-acquired MR scan to boost the performance of MAR algorithms.

Background MRI-only radiotherapy will eliminate the systematic registration errors introduced when transferring MRI information to the CT. However, challenges concerning the missing information on electron density, necessary for dose calculation and patient setup on bony anatomy are introduced. This study presents a possible statistical approach to evaluate, if deviations based on MRI-only radiotherapy as compared to the CT based radiotherapy are acceptable. Methods 18 head-and-neck, 21 prostate, 10 vesica and 8 pelvic patients were included in the study. Data from each patient contained a CT and a T2-weighted MRI scan, a structure set and a clinically approved CT based treatment plan, which was re-calculated with identical parameters on the density corrected MRI scans. A statistical analysis including a 95% confidence interval was performed in clinically relevant DVH points. Results The mean differences in the investigated DVH points were in the order of 1.5% for the PTV and up to 4.2% for organs at risk. In addition, a proposed criterion of 2% dose difference in the PTV coverage for 95% of the patients was fulfilled for all diagnostic groups for a bulk segmented MRI in the DVH points, Dmedian and D2%, while only head-and-neck and prostate further fulfilled the criterion in D98%. Conclusion Here, we suggested a method for establishing a reliable use of MRI-only radiotherapy. A population-based study comparing CT based dose calculations with those obtained on a suggested segmentation of MRI should be initiated and acceptable deviations in clinically relevant DVH points should be established. Such a population-based approach could form a part of the clinical commissioning of MRI-only radiotherapy.