Magnetic resonance Imaging is the gold standard for assessment of soft tissues; however, X-ray-based techniques are required for evaluating bone-related pathologies. This study evaluated the performance of synthetic computed tomography (sCT), a novel MRI-based bone visualization technique, compared with CT, for the scoring of knee osteoarthritis. sCT images were generated from the 3T T1-weighted gradient-echo MR images using a trained machine learning algorithm. Two readers scored the severity of osteoarthritis in tibiofemoral and patellofemoral joints according to OACT, which enables the evaluation of osteoarthritis, from its characteristics of joint space narrowing, osteophytes, cysts and sclerosis in CT (and sCT) images. Cohen's κ was used to assess the interreader agreement for each modality, and intermodality agreement of CT- and sCT-based scores for each reader. We also compared the confidence level of readers for grading CT and sCT images using confidence scores collected during grading. Inter-reader agreement for tibiofemoral and patellofemoral joints were almost-perfect for both modalities (κ = 0.83–0.88). The intermodality agreement of osteoarthritis scores between CT and sCT was substantial to almost-perfect for tibiofemoral (κ = 0.63 and 0.84 for the two readers) and patellofemoral joints (κ = 0.78 and 0.81 for the two readers). The analysis of diagnosis confidence scores showed comparable visual quality of the two modalities, where both are showing acceptable confidence levels for scoring OA. In conclusion, in this single-center study, sCT and CT were comparable for the scoring of knee OA.

Diffuse idiopathic skeletal hyperostosis (DISH) is often theorized to be an ossification of the anterior longitudinal ligament (ALL). Using computed tomography (CT) imaging and cryomacrotome sectioning, we investigated the spatial relationship between the ALL and newly formed bone in DISH to test this hypothesis. In the current study, four human cadaveric spines diagnosed with DISH using CT imaging were frozen and sectioned using a cryomacrotome. Photographs were obtained of the specimen at 125 µm intervals. Manual segmentations of the ALL on cryomacrotome photographs were projected onto the three-dimensional reconstructed CT scans. The presence and location of newly formed bone were assessed in relationship to the location of the ALL. The ALL could be identified and segmented on the photographs at all levels. The ALL was located at the midline at levels where no new bone had formed. At the locations where new bone had abundantly formed, the ALL was displaced towards to the contralateral side and not replaced by bony tissue. The displacement of the—morphologically normal appearing—ALL away from the newly formed bone implies that newly formed bone in DISH may not originate from the ALL.

Predicting pseudo CT images from MRI data has received increasing attention for use in MRI-only radiation therapy planning and PET-MRI attenuation correction, eliminating the need for harmful CT scanning. Current approaches focus on voxelwise mean absolute error (MAE) and peak signal-to-noise-ratio (PSNR) for optimization and evaluation. Contextual losses such as structural similarity (SSIM) are known to promote perceptual image quality. We investigate the use of these contextual losses for optimization. Patch-based 3D fully convolutional neural networks (FCN) were optimized for prediction of pseudo CT images from 3D gradient echo pelvic MRI data and compared to ground truth CT data of 26 patients. CT data was non-rigidly registered to MRI for training and evaluation. We compared voxelwise L1 and L2 loss functions, with contextual multi-scale L1 and L2 (MSL1 and MSL2), and SSIM. Performance was evaluated using MAE, PSNR, SSIM and the overlap of segmented cortical bone in the reconstructions, by the dice similarity metric. Evaluation was carried out in cross-validation. All optimizations successfully converged well with PSNR between 25 and 30 HU, except for one of the folds of SSIM optimizations. MSL1 and MSL2 are at least on par with their single-scale counterparts. MSL1 overcomes some of the instabilities of the L1 optimized prediction models. MSL2 optimization is stable, and on average, outperforms all the other losses, although quantitative evaluations based on MAE, PSNR and SSIM only show minor differences. Direct optimization using SSIM visually excelled in terms subjective perceptual image quality at the expense of a voxelwise quantitative performance drop. Contextual loss functions can improve prediction performance of FCNs without change of the network architecture. The suggested subjective superiority of contextual losses in reconstructing local structures merits further investigations.

Background: In this study, our aim was to identify molecular aberrations predictive for response to everolimus, an mTOR inhibitor, regardless of tumor type. Methods: To generate hypotheses about potential markers for sensitivity to mTOR inhibition, drug sensitivity and genomic profiles of 835 cell lines were analyzed. Subsequently, a multicenter study was conducted. Patients with advanced solid tumors lacking standard of care treatment options were included and underwent a pre-treatment tumor biopsy to enable DNA sequencing of 1,977 genes, derive copy number profiles and determine activation status of pS6 and pERK. Treatment benefit was determined according to TTP ratio and RECIST. We tested for associations between treatment benefit and single molecular aberrations, clusters of aberrations and pathway perturbation. Results: Cell line screens indicated several genes, such as PTEN (P = 0.016; Wald test), to be associated with sensitivity to mTOR inhibition. Subsequently 73 patients were included, of which 59 started treatment with everolimus. Response and molecular data were available from 43 patients. PTEN aberrations, i.e. copy number loss or mutation, were associated with treatment benefit (P = 0.046; Fisher's exact test). Conclusion: Loss-of-function aberrations in PTEN potentially represent a tumor type agnostic biomarker for benefit from everolimus and warrants further confirmation in subsequent studies.