Quantification of cervical spinal stenosis by automated 3D MRI segmentation of spinal cord and cerebrospinal fluid space.

DESIGN: Prospective diagnostic study. OBJECTIVES: Anatomical evaluation and graduation of the severity of spinal stenosis is essential in degenerative cervical spine disease. In clinical practice, this is subjectively categorized on cervical MRI lacking an objective and reliable classification. We implemented a fully-automated quantification of spinal canal compromise through 3D T2-weighted MRI segmentation. SETTING: Medical Center - University of Freiburg, Germany. METHODS: Evaluation of 202 participants receiving 3D T2-weighted MRI of the cervical spine. Segments C2/3 to C6/7 were analyzed for spinal cord and cerebrospinal fluid space volume through a fully-automated segmentation based on a trained deep convolutional neural network. Spinal canal narrowing was characterized by relative values, across sever segments as adapted Maximal Canal Compromise (aMCC), and within the index segment as adapted Spinal Cord Occupation Ratio (aSCOR). Additionally, all segments were subjectively categorized by three observers as "no", "relative" or "absolute" stenosis. Computed scores were applied on the subjective categorization. RESULTS: 798 (79.0%) segments were subjectively categorized as "no" stenosis, 85 (8.4%) as "relative" stenosis, and 127 (12.6%) as "absolute" stenosis. The calculated scores revealed significant differences between each category (p ≤ 0.001). Youden's Index analysis of ROC curves revealed optimal cut-offs to distinguish between "no" and "relative" stenosis for aMCC = 1.18 and aSCOR = 36.9%, and between "relative" and "absolute" stenosis for aMCC = 1.54 and aSCOR = 49.3%. CONCLUSION: The presented fully-automated segmentation algorithm provides high diagnostic accuracy and objective classification of cervical spinal stenosis. The calculated cut-offs can be used for convenient radiological quantification of the severity of spinal canal compromise in clinical routine.

Automated signal intensity analysis of the spinal cord for detection of degenerative cervical myelopathy - a matched-pair MRI study.

PURPOSE: Detection of T2 hyperintensities in suspected degenerative cervical myelopathy (DCM) is done subjectively in clinical practice. To gain objective quantification for dedicated treatment, signal intensity analysis of the spinal cord is purposeful. We investigated fully automated quantification of the T2 signal intensity (T2-SI) of the spinal cord using a high-resolution MRI segmentation. METHODS: Matched-pair analysis of prospective acquired cervical 3D T2-weighted sequences of 114 symptomatic patients and 88 healthy volunteers. Cervical spinal cord was segmented automatically through a trained convolutional neuronal network with subsequent T2-SI registration slice-by-slice. Received T2-SI curves were subdivided for each cervical level from C2 to C7. Additionally, all levels were subjectively classified concerning a present T2 hyperintensity. For T2-positive levels, corresponding T2-SI curves were compared to curves of age-matched volunteers at the identical level. RESULTS: Forty-nine patients showed subjective T2 hyperintensities at any level. The corresponding T2-SI curves showed higher signal variabilities reflected by standard deviation (18.51 vs. 7.47 a.u.; p < 0.001) and range (56.09 vs. 24.34 a.u.; p < 0.001) compared to matched controls. Percentage of the range from the mean absolute T2-SI per cervical level, introduced as "T2 myelopathy index" (T2-MI), was correspondingly significantly higher in T2-positive segments (23.99% vs. 10.85%; p < 0.001). ROC analysis indicated excellent differentiation for all three parameters (AUC 0.865-0.920). CONCLUSION: This fully automated T2-SI quantification of the spinal cord revealed significantly increased signal variability for DCM patients compared to healthy volunteers. This innovative procedure and the applied parameters showed sufficient diagnostic accuracy, potentially diagnosing radiological DCM more objective to optimize treatment recommendation. TRIAL REGISTRATION: DRKS00012962 (17.01.2018) and DRKS00017351 (28.05.2019).

[The Neonatal Subgaleal Hematoma - A Neonatal Emergency]. / Das subgaleale Hämatom beim Neugeborenen ­ ein neonatologischer Notfall.

Subgaleal hematoma (SGH) is a rare complication in neonates that may lead to hemorrhagic shock due to significant blood loss into the subgaleal space. We report of two neonates who developed subgaleal hematoma with severe hemorrhagic shock and encephalopathy. In the first case of a mature female neonate, the development of the subgaleal hematoma was promoted by early-onset sepsis and delivery by vacuum extraction. The second case, of a male preterm neonate, was a complicated fetal development followed by secondary cesarean section. Both cases highlight that a subgaleal hematoma is a severe neonatal emergency. In addition to prompt treatment of the shock, therapy of the coagulopathy is essential.

SPectroscOpic prediction of bRain Tumours (SPORT): study protocol of a prospective imaging trial.

BACKGROUND: The revised 2016 WHO-Classification of CNS-tumours now integrates molecular information of glial brain tumours for accurate diagnosis as well as for the development of targeted therapies. In this prospective study, our aim is to investigate the predictive value of MR-spectroscopy in order to establish a solid preoperative molecular stratification algorithm of these tumours. We will process a 1H MR-spectroscopy sequence within a radiomics analytics pipeline. METHODS: Patients treated at our institution with WHO-Grade II, III and IV gliomas will receive preoperative anatomical (T2- and T1-weighted imaging with and without contrast enhancement) and proton MR spectroscopy (MRS) by using chemical shift imaging (MRS) (5 × 5 × 15 mm3 voxel size). Tumour regions will be segmented and co-registered to corresponding spectroscopic voxels. Raw signals will be processed by a deep-learning approach for identifying patterns in metabolic data that provides information with respect to the histological diagnosis as well patient characteristics obtained and genomic data such as target sequencing and transcriptional data. DISCUSSION: By imaging the metabolic profile of a glioma using a customized chemical shift 1H MR spectroscopy sequence and by processing the metabolic profiles with a machine learning tool we intend to non-invasively uncover the genetic signature of gliomas. This work-up will support surgical and oncological decisions to improve personalized tumour treatment. TRIAL REGISTRATION: This study was initially registered under another name and was later retrospectively registered under the current name at the German Clinical Trials Register (DRKS) under DRKS00019855.

MR-spectroscopic imaging of glial tumors in the spotlight of the 2016 WHO classification.

BACKGROUND: The purpose of this study is to map spatial metabolite differences across three molecular subgroups of glial tumors, defined by the IDH1/2 mutation and 1p19q-co-deletion, using magnetic resonance spectroscopy. This work reports a new MR spectroscopy based classification algorithm by applying a radiomics analytics pipeline. MATERIALS: 65 patients received anatomical and chemical shift imaging (5 × 5 × 20 mm voxel size). Tumor regions were segmented and registered to corresponding spectroscopic voxels. Spectroscopic features were computed (n = 860) in a radiomic approach and selected by a classification algorithm. Finally, a random forest machine-learning model was trained to predict the molecular subtypes. RESULTS: A cluster analysis identified three robust spectroscopic clusters based on the mean silhouette widths. Molecular subgroups were significantly associated with the computed spectroscopic clusters (Fisher's Exact test p < 0.01). A machine-learning model was trained and validated by public available MRS data (n = 19). The analysis showed an accuracy rate in the Random Forest model by 93.8%. CONCLUSIONS: MR spectroscopy is a robust tool for predicting the molecular subtype in gliomas and adds important diagnostic information to the preoperative diagnostic work-up of glial tumor patients. MR-spectroscopy could improve radiological diagnostics in the future and potentially influence clinical and surgical decisions to improve individual tumor treatment.

Advanced diffusion imaging reveals microstructural characteristics of primary CNS lymphoma, allowing differentiation from glioblastoma.

Background: Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL from GBM with conventional MRI can be challenging when atypical imaging features are present. We employed advanced dMRI for noninvasive characterization of the microstructure of PCNSL and differentiation from GBM as the most frequent primary brain malignancy. Methods: Multiple dMRI metrics including Diffusion Tensor Imaging, Neurite Orientation Dispersion and Density Imaging, and Diffusion Microstructure Imaging were extracted from the contrast-enhancing tumor component in 10 PCNSL and 10 age-matched GBM on 3T MRI. Imaging findings were correlated with cell density and axonal markers obtained from histopathology. Results: We found significantly increased intra-axonal volume fractions (V-intra and intracellular volume fraction) and microFA in PCNSL compared to GBM (all P < .001). In contrast, mean diffusivity (MD), axial diffusivity (aD), and microADC (all P < .001), and also free water fractions (V-CSF and V-ISO) were significantly lower in PCNSL (all P < .01). Receiver-operating characteristic analysis revealed high predictive values regarding the presence of a PCNSL for MD, aD, microADC, V-intra, ICVF, microFA, V-CSF, and V-ISO (area under the curve [AUC] in all >0.840, highest for MD and ICVF with an AUC of 0.960). Comparative histopathology between PCNSL and GBM revealed a significantly increased cell density in PCNSL and the presence of axonal remnants in a higher proportion of samples. Conclusions: Advanced diffusion imaging enables the characterization of the microstructure of PCNSL and reliably distinguishes PCNSL from GBM. Both imaging and histopathology revealed a relatively increased cell density and a preserved axonal microstructure in PCNSL.

Improved early outcome prediction by MRI-based 3D tumor volume assessment in patients with CNS lymphomas.

BACKGROUND: Central nervous system lymphomas (CNSL) display remarkable clinical heterogeneity, yet accurate prediction of outcomes remains challenging. The IPCG criteria are widely used in routine practice for the assessment of treatment response. However, the value of the IPCG criteria for ultimate outcome prediction is largely unclear, mainly due to the uncertainty in delineating complete from partial responses during and after treatment. METHODS: We explored various MRI features including semi-automated 3D tumor volume measurements at different disease milestones and their association with survival in 93 CNSL patients undergoing curative-intent treatment. RESULTS: At diagnosis, patients with more than 3 lymphoma lesions, periventricular involvement, and high 3D tumor volumes showed significantly unfavorable PFS and OS. At first interim MRI during treatment, the IPCG criteria failed to discriminate outcomes in responding patients. Therefore, we randomized these patients into training and validation cohorts to investigate whether 3D tumor volumetry could improve outcome prediction. We identified a 3D tumor volume reduction of ≥97% as the optimal threshold for risk stratification (=3D early response, 3D_ER). Applied to the validation cohort, patients achieving 3D_ER had significantly superior outcomes. In multivariate analyses, 3D_ER was independently prognostic of PFS and OS. Finally, we leveraged prognostic information from 3D MRI features and circulating biomarkers to build a composite metric that further improved outcome prediction in CNSL. CONCLUSIONS: We developed semi-automated 3D tumor volume measurements as strong and independent early predictors of clinical outcomes in CNSL patients. These radiologic features could help improve risk stratification and help guide future treatment approaches.

Mesoscopic Assessment of Microstructure in Glioblastomas and Metastases by Merging Advanced Diffusion Imaging with Immunohistopathology.

BACKGROUND AND PURPOSE: Glioblastomas and metastases are the most common malignant intra-axial brain tumors in adults and can be difficult to distinguish on conventional MR imaging due to similar imaging features. We used advanced diffusion techniques and structural histopathology to distinguish these tumor entities on the basis of microstructural axonal and fibrillar signatures in the contrast-enhancing tumor component. MATERIALS AND METHODS: Contrast-enhancing tumor components were analyzed in 22 glioblastomas and 21 brain metastases on 3T MR imaging using DTI-fractional anisotropy, neurite orientation dispersion and density imaging-orientation dispersion, and diffusion microstructural imaging-micro-fractional anisotropy. Available histopathologic specimens (10 glioblastomas and 9 metastases) were assessed for the presence of axonal structures and scored using 4-level scales for Bielschowsky staining (0: no axonal structures, 1: minimal axonal fragments preserved, 2: decreased axonal density, 3: no axonal loss) and glial fibrillary acid protein expression (0: no glial fibrillary acid protein positivity, 1: limited expression, 2: equivalent to surrounding parenchyma, 3: increased expression). RESULTS: When we compared glioblastomas and metastases, fractional anisotropy was significantly increased and orientation dispersion was decreased in glioblastomas (each P < .001), with a significant shift toward increased glial fibrillary acid protein and Bielschowsky scores. Positive associations of fractional anisotropy and negative associations of orientation dispersion with glial fibrillary acid protein and Bielschowsky scores were revealed, whereas no association between micro-fractional anisotropy with glial fibrillary acid protein and Bielschowsky scores was detected. Receiver operating characteristic curves revealed high predictive values of both fractional anisotropy (area under the curve = 0.8463) and orientation dispersion (area under the curve = 0.8398) regarding the presence of a glioblastoma. CONCLUSIONS: Diffusion imaging fractional anisotropy and orientation dispersion metrics correlated with histopathologic markers of directionality and may serve as imaging biomarkers in contrast-enhancing tumor components.

Direct comparison of digital subtraction myelography versus CT myelography in lateral decubitus position: evaluation of diagnostic yield for cerebrospinal fluid-venous fistulas.

BACKGROUND: Cerebrospinal fluid (CSF)-venous fistulas (CVFs) are increasingly identified as a cause of spontaneous intracranial hypotension (SIH). Lateral decubitus digital subtraction myelography (LD-DSM) and CT myelography (LD-CTM) are mainly used for detection, but the most sensitive method is yet unknown. OBJECTIVE: To compare LD-DSM with LD-CTM for diagnostic yield of CVFs. METHODS: Patients with SIH diagnosed with a CVF between January 2021 and December 2022 in which the area of CVF(s) was covered by both diagnostic modalities were included. LD-CTM immediately followed LD-DSM without repositioning the spinal needle, and the second half of the contrast agent was injected at the CT scanner. Patients were awake or mildly sedated. Retrospectively, two neuroradiologists evaluated data independently and blinded for the presence of CVF. RESULTS: Twenty patients underwent a total of 27 combined LD-DSM/LD-CTM examinations (4/20 with follow-up and 3/20 with bilateral examinations). Both raters identified significantly more CVFs with LD-CTM than with LD-DSM (rater 1: 39 vs 9, P<0.001; rater 2: 42 vs 12, P<0.001). Inter-rater agreement was substantial for LD-DSM (κ=0.732) and LD-CTM (κ=0.655). The results remained significant after considering the senior rating for cases of disagreement (39 vs 10; P<0.001), and no CVF detected on LD-DSM was missed on LD-CTM. CONCLUSION: In this study, LD-CTM has a higher diagnostic yield for the detection of CVFs than LD-DSM and should supplement LD-DSM, but further studies are needed. LD-CTM can be easily acquired in awake or mildly sedated patients with the second half of contrast injected just before CT scanning, or it may be considered as a stand-alone investigation.

Diffusion Microstructure Imaging to Analyze Perilesional T2 Signal Changes in Brain Metastases and Glioblastomas.

Purpose: Glioblastomas (GBM) and brain metastases are often difficult to differentiate in conventional MRI. Diffusion microstructure imaging (DMI) is a novel MR technique that allows the approximation of the distribution of the intra-axonal compartment, the extra-axonal cellular, and the compartment of interstitial/free water within the white matter. We hypothesize that alterations in the T2 hyperintense areas surrounding contrast-enhancing tumor components may be used to differentiate GBM from metastases. Methods: DMI was performed in 19 patients with glioblastomas and 17 with metastatic lesions. DMI metrics were obtained from the T2 hyperintense areas surrounding contrast-enhancing tumor components. Resected brain tissue was assessed in six patients in each group for features of an edema pattern and tumor infiltration in the perilesional interstitium. Results: Within the perimetastatic T2 hyperintensities, we observed a significant increase in free water (p < 0.001) and a decrease in both the intra-axonal (p = 0.006) and extra-axonal compartments (p = 0.024) compared to GBM. Perilesional free water fraction was discriminative regarding the presence of GBM vs. metastasis with a ROC AUC of 0.824. Histologically, features of perilesional edema were present in all assessed metastases and absent or marginal in GBM. Conclusion: Perilesional T2 hyperintensities in brain metastases and GBM differ significantly in DMI-values. The increased free water fraction in brain metastases suits the histopathologically based hypothesis of perimetastatic vasogenic edema, whereas in glioblastomas there is additional tumor infiltration.

Differentiation of Perilesional Edema in Glioblastomas and Brain Metastases: Comparison of Diffusion Tensor Imaging, Neurite Orientation Dispersion and Density Imaging and Diffusion Microstructure Imaging.

Although the free water content within the perilesional T2 hyperintense region should differ between glioblastomas (GBM) and brain metastases based on histological differences, the application of classical MR diffusion models has led to inconsistent results regarding the differentiation between these two entities. Whereas diffusion tensor imaging (DTI) considers the voxel as a single compartment, multicompartment approaches such as neurite orientation dispersion and density imaging (NODDI) or the recently introduced diffusion microstructure imaging (DMI) allow for the calculation of the relative proportions of intra- and extra-axonal and also free water compartments in brain tissue. We investigate the potential of water-sensitive DTI, NODDI and DMI metrics to detect differences in free water content of the perilesional T2 hyperintense area between histopathologically confirmed GBM and brain metastases. Respective diffusion metrics most susceptible to alterations in the free water content (MD, V-ISO, V-CSF) were extracted from T2 hyperintense perilesional areas, normalized and compared in 24 patients with GBM and 25 with brain metastases. DTI MD was significantly increased in metastases (p = 0.006) compared to GBM, which was corroborated by an increased DMI V-CSF (p = 0.001), while the NODDI-derived ISO-VF showed only trend level increase in metastases not reaching significance (p = 0.060). In conclusion, diffusion MRI metrics are able to detect subtle differences in the free water content of perilesional T2 hyperintense areas in GBM and metastases, whereas DMI seems to be superior to DTI and NODDI.