Thomas Asklund

Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review

The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab produces an improvement or preservation of neurocognitive function in GBM patients, suggestive of QoL improvement, in most poor-prognosis patients who would otherwise be expected to show a sudden and rapid deterioration in QoL.

Voxel-wise uncertainty in CT substitute derived from MRI.

PURPOSE In an earlier work, we demonstrated that substitutes for CT images can be derived from MR images using ultrashort echo time (UTE) sequences, conventional T2 weighted sequences, and Gaussian mixture regression (GMR). In this study, we extend this work by analyzing the uncertainties associated with the GMR model and the information contributions from the individual imaging sequences. METHODS An analytical expression for the voxel-wise conditional expected absolute deviation (EAD) in substitute CT (s-CT) images was derived. The expression depends only on MR images and can thus be calculated along with each s-CT image. The uncertainty measure was evaluated by comparing the EAD to the true mean absolute prediction deviation (MAPD) between the s-CT and CT images for 14 patients. Further, the influence of the different MR images included in the GMR model on the generated s-CTs was investigated by removing one or more images and evaluating the MAPD for a spectrum of predicted radiological densities. RESULTS The largest EAD was predicted at air-soft tissue and bone-soft tissue interfaces. The EAD agreed with the MAPD in both these regions and in regions with lower EADs, such as the brain. Two of the MR images included in the GMR model were found to be mutually redundant for the purpose of s-CT generation. CONCLUSIONS The presented uncertainty estimation method accurately predicts the voxel-wise MAPD in s-CT images. Also, the non-UTE sequence previously used in the model was found to be redundant.

Improved quality of computed tomography substitute derived from magnetic resonance (MR) data by incorporation of spatial information – potential application for MR-only radiotherapy and attenuation correction in positron emission tomography

Abstract Background. Estimation of computed tomography (CT) equivalent data, i.e. a substitute CT (s-CT), from magnetic resonance (MR) images is a prerequisite both for attenuation correction of positron emission tomography (PET) data acquired with a PET/MR scanner and for dose calculations in an MR-only radiotherapy workflow. It has previously been shown that it is possible to estimate Hounsfield numbers based on MR image intensities, using ultra short echo-time imaging and Gaussian mixture regression (GMR). In the present pilot study we investigate the possibility to also include spatial information in the GMR, with the aim to improve the quality of the s-CT. Material and methods. MR and CT data for nine patients were used in the present study. For each patient, GMR models were created from the other eight patients, including either both UTE image intensities and spatial information on a voxel by voxel level, or only UTE image intensities. The models were used to create s-CT images for each respective patient. Results. The inclusion of spatial information in the GMR model improved the accuracy of the estimated s-CT. The improvement was most pronounced in smaller, complicated anatomical regions as the inner ear and post-nasal cavities. Conclusions. This pilot study shows that inclusion of spatial information in GMR models to convert MR data to CT equivalent images is feasible. The accuracy of the s-CT is improved and the spatial information could make it possible to create a general model for the conversion applicable to the whole body.

Treatment planning of intracranial targets on MRI derived substitute CT data

BACKGROUND The use of magnetic resonance imaging (MRI) as a complement to computed tomography (CT) in the target definition procedure for radiotherapy is increasing. To eliminate systematic uncertainties due to image registration, a workflow based entirely on MRI may be preferable. In the present pilot study, we investigate dose calculation accuracy for automatically generated substitute CT (s-CT) images of the head based on MRI. We also produce digitally reconstructed radiographs (DRRs) from s-CT data to evaluate the feasibility of patient positioning based on MR images. METHODS AND MATERIALS Five patients were included in the study. The dose calculation was performed on CT, s-CT, s-CT data without inhomogeneity correction and bulk density assigned MRI images. Evaluation of the results was performed using point dose and dose volume histogram (DVH) comparisons, and gamma index evaluation. RESULTS The results demonstrate that the s-CT images improve the dose calculation accuracy compared to the method of non-inhomogeneity corrected dose calculations (mean improvement 2.0% points) and that it performs almost identically to the method of bulk density assignment. The s-CT based DRRs appear to be adequate for patient positioning of intra-cranial targets, although further investigation is needed on this subject. CONCLUSION The s-CT method is very fast and yields data that can be used for treatment planning without sacrificing accuracy.

ADC texture—An imaging biomarker for high‐grade glioma?

PURPOSE Survival for high-grade gliomas is poor, at least partly explained by intratumoral heterogeneity contributing to treatment resistance. Radiological evaluation of treatment response is in most cases limited to assessment of tumor size months after the initiation of therapy. Diffusion-weighted magnetic resonance imaging (MRI) and its estimate of the apparent diffusion coefficient (ADC) has been widely investigated, as it reflects tumor cellularity and proliferation. The aim of this study was to investigate texture analysis of ADC images in conjunction with multivariate image analysis as a means for identification of pretreatment imaging biomarkers. METHODS Twenty-three consecutive high-grade glioma patients were treated with radiotherapy (2 Gy/60 Gy) with concomitant and adjuvant temozolomide. ADC maps and T1-weighted anatomical images with and without contrast enhancement were collected prior to treatment, and (residual) tumor contrast enhancement was delineated. A gray-level co-occurrence matrix analysis was performed on the ADC maps in a cuboid encapsulating the tumor in coronal, sagittal, and transversal planes, giving a total of 60 textural descriptors for each tumor. In addition, similar examinations and analyses were performed at day 1, week 2, and week 6 into treatment. Principal component analysis (PCA) was applied to reduce dimensionality of the data, and the five largest components (scores) were used in subsequent analyses. MRI assessment three months after completion of radiochemotherapy was used for classifying tumor progression or regression. RESULTS The score scatter plots revealed that the first, third, and fifth components of the pretreatment examinations exhibited a pattern that strongly correlated to survival. Two groups could be identified: one with a median survival after diagnosis of 1099 days and one with 345 days, p = 0.0001. CONCLUSIONS By combining PCA and texture analysis, ADC texture characteristics were identified, which seems to hold pretreatment prognostic information, independent of known prognostic factors such as age, stage, and surgical procedure. These findings encourage further studies with a larger patient cohort.

Brain tumors in Sweden: Data from a population-based registry 1999–2012

Abstract Background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research. Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre- and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse. Results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60–69. Patients aged 18–39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables. Conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.

CT substitutes derived from MR images reconstructed with parallel imaging.

PURPOSE Computed tomography (CT) substitute images can be generated from ultrashort echo time (UTE) MRI sequences with radial k-space sampling. These CT substitutes can be used as ordinary CT images for PET attenuation correction and radiotherapy dose calculations. Parallel imaging allows faster acquisition of magnetic resonance (MR) images by exploiting differences in receiver coil element sensitivities. This study investigates whether non-Cartesian parallel imaging reconstruction can be used to improve CT substitutes generated from shorter examination times. METHODS The authors used gridding as well as two non-Cartesian parallel imaging reconstruction methods, SPIRiT and CG-SENSE, to reconstruct radial UTE and gradient echo (GE) data into images of the head for 23 patients. For each patient, images were reconstructed from the full dataset and from a number of subsampled datasets. The subsampled datasets simulated shorter acquisition times by containing fewer radial k-space spokes (1000, 2000, 3000, 5000, and 10,000 spokes) than the full dataset (30,000 spokes). For each combination of patient, reconstruction method, and number of spokes, the reconstructed UTE and GE images were used to generate a CT substitute. Each CT substitute image was compared to a real CT image of the same patient. RESULTS The mean absolute deviation between the CT number in CT substitute and CT decreased when using SPIRiT as compared to gridding reconstruction. However, the reduction was small and the CT substitute algorithm was insensitive to moderate subsampling (≥ 5000 spokes) regardless of reconstruction method. For more severe subsampling (≤ 3000 spokes), corresponding to acquisition times less than a minute long, the CT substitute quality was deteriorated for all reconstruction methods but SPIRiT gave a reduction in the mean absolute deviation of down to 25 Hounsfield units compared to gridding. CONCLUSIONS SPIRiT marginally improved the CT substitute quality for a given number of radial spokes as compared to gridding. However, the increased reconstruction time of non-Cartesian parallel imaging reconstruction is difficult to motivate from this improvement. Because the CT substitute algorithm was insensitive to moderate subsampling, data for a CT substitute could be collected in as little as minute and reconstructed with gridding without deteriorating the CT substitute quality.

Durable stabilization of three chordoma cases by bevacizumab and erlotinib

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Uncertainty estimation in dynamic contrast-enhanced MRI

Using dynamic contrast‐enhanced MRI (DCE‐MRI), it is possible to estimate pharmacokinetic (PK) parameters that convey information about physiological properties, e.g., in tumors. In DCE‐MRI, errors propagate in a nontrivial way to the PK parameters. We propose a method based on multivariate linear error propagation to calculate uncertainty maps for the PK parameters. Uncertainties in the PK parameters were investigated for the modified Kety model. The method was evaluated with Monte Carlo simulations and exemplified with in vivo brain tumor data. PK parameter uncertainties due to noise in dynamic data were accurately estimated. Noise with standard deviation up to 15% in the baseline signal and the baseline T1 map gave estimated uncertainties in good agreement with the Monte Carlo simulations. Good agreement was also found for up to 15% errors in the arterial input function amplitude. The method was less accurate for errors in the bolus arrival time with disagreements of 23%, 32%, and 29% for Ktrans, ve, and vp, respectively, when the standard deviation of the bolus arrival time error was 5.3 s. In conclusion, the proposed method provides efficient means for calculation of uncertainty maps, and it was applicable to a wide range of sources of uncertainty. Magn Reson Med 69:992–1002, 2013.

Radiotherapy and pacemaker : 80 Gy to target close to the device may be feasible.

Modern pacemakers using complementary metal-oxide semiconductors (CMOS) technology are sensitive to radiation. The guidelines recommend caution at doses above 2 Gray (Gy). Repositioning should be discussed if cumulative dose and dose rate exceeds 10 and 0.2 Gy/min. We report a case of a man with mechanical mitral valve prosthesis and pacemaker due to sick sinus syndrome …