Cortical myelin and thickness mapping provide insights into whole-brain tumor burden in diffuse midline glioma.

Systemic infiltration is a hallmark of diffuse midline glioma pathogenesis, which can trigger distant disturbances in cortical structure. However, the existence and effects of these changes have been underexamined. This study aimed to investigate whole-brain cortical myelin and thickness alternations induced by diffuse midline glioma. High-resolution T1- and T2-weighted images were acquired from 90 patients with diffuse midline glioma with H3 K27-altered and 64 patients with wild-type and 86 healthy controls. Cortical thickness and myelin content was calculated using Human Connectome Project pipeline. Significant differences in cortical thickness and myelin content were detected among groups. Short-term survival prediction model was constructed using automated machine learning. Compared with healthy controls, diffuse midline glioma with H3 K27-altered patients showed significantly reduced cortical myelin in bilateral precentral gyrus, postcentral gyrus, insular, parahippocampal gyrus, fusiform gyrus, and cingulate gyrus, whereas diffuse midline glioma with H3 K27 wild-type patients exhibited well-preserved myelin content. Furtherly, when comparing diffuse midline glioma with H3 K27-altered and diffuse midline glioma with H3 K27 wild-type, the decreased cortical thickness in parietal and occipital regions along with demyelination in medial orbitofrontal cortex was observed in diffuse midline glioma with H3 K27-altered. Notably, a combination of cortical features and tumor radiomics allowed short-term survival prediction with accuracy 0.80 and AUC 0.84. These findings may aid clinicians in tailoring therapeutic approaches based on cortical characteristics, potentially enhancing the efficacy of current and future treatment modalities.

Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.

Recurrent, clonal somatic mutations in histone H3 are molecular hallmarks that distinguish the genetic mechanisms underlying pediatric and adult high-grade glioma (HGG), define biological subgroups of diffuse glioma, and highlight connections between cancer, development, and epigenetics. These oncogenic mutations in histones, now termed "oncohistones", were discovered through genome-wide sequencing of pediatric diffuse high-grade glioma. Up to 80% of diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG) and diffuse glioma arising in other midline structures including thalamus or spinal cord, contain histone H3 lysine 27 to methionine (K27M) mutations or, rarely, other alterations that result in a depletion of H3K27me3 similar to that induced by H3 K27M. This subgroup of glioma is now defined as diffuse midline glioma, H3K27-altered. In contrast, histone H3 Gly34Arg/Val (G34R/V) mutations are found in approximately 30% of diffuse glioma arising in the cerebral hemispheres of older adolescents and young adults, now classified as diffuse hemispheric glioma, H3G34-mutant. Here, we review how oncohistones modulate the epigenome and discuss the mutational landscape and invasive properties of histone mutant HGGs of childhood. The distinct mechanisms through which oncohistones and other mutations rewrite the epigenetic landscape provide novel insights into development and tumorigenesis and may present unique vulnerabilities for pHGGs. Lessons learned from these rare incurable brain tumors of childhood may have broader implications for cancer, as additional high- and low-frequency oncohistone mutations have been identified in other tumor types.

Focused ultrasound-mediated blood-brain barrier opening is safe and feasible with moderately hypofractionated radiotherapy for brainstem diffuse midline glioma.

BACKGROUND: Diffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood-brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS). Focused ultrasound (FUS) with microbubbles can transiently and non-invasively disrupt the BBB to enhance drug delivery. This study aimed to determine the feasibility of brainstem FUS in combination with clinical doses of RT. We hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT. METHODS: To establish a safety timeline, we administered FUS to the brainstem of non-tumor bearing mice concurrent with or adjuvant to RT; our findings were validated in a syngeneic brainstem murine model of DMG receiving repeated sonication concurrent with RT. The brainstems of male B6 (Cg)-Tyrc-2J/J albino mice were intracranially injected with mouse DMG cells (PDGFB+, H3.3K27M, p53-/-). A clinical RT dose of 39 Gy in 13 fractions (39 Gy/13fx) was delivered using the Small Animal Radiation Research Platform (SARRP) or XRAD-320 irradiator. FUS was administered via a 0.5 MHz transducer, with BBBO and tumor volume monitored by magnetic resonance imaging (MRI). RESULTS: FUS-mediated BBBO did not affect cardiorespiratory rate, motor function, or tissue integrity in non-tumor bearing mice receiving RT. Tumor-bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy/13fx offered local control, though disease progression occurred 3-4 weeks post-RT. CONCLUSION: Repeated FUS-mediated BBBO is safe and feasible concurrent with RT. In our syngeneic DMG murine model, progression occurs, serving as an ideal model for future combination testing with RT and FUS-mediated drug delivery.

Reirradiation for diffuse intrinsic pontine glioma: prognostic radiomic factors at progression.

PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor. Radiation therapy (RT) is the standard treatment, with reirradiation considered in case of progression. However, the prognostic factors for reirradiation are not well understood. This study aims to investigate the outcomes of DIPG patients undergoing reirradiation and identify clinical and radiomic prognostic factors. METHODS: We conducted a retrospective analysis of patients with DIPG who underwent reirradiation at our institution between January 2016 and December 2023. Using PyRadiomics, we extracted radiomic features of tumors at the time of progression from FLAIR MRI images and collected clinical data. We used the least absolute shrinkage and selection operator (lasso) for Cox's proportional hazard model with leave-one-out cross-validation to select optimal prognostic factors for survival after reirradiation. RESULTS: The study included 18 patients who underwent reirradiation at first progression, receiving a total dose of 20 Gy or 24 Gy in 2­Gy fractions. Reirradiation was well tolerated, with no severe toxicity. Most patients (78%) showed neurological improvement after treatment. Median survival after progression was 29.2 weeks. The Cox model demonstrated a concordance of 0.81 (95% CI: 0.75-0.88), revealing that tumor sphericity and structural gray-level heterogeneity in FLAIR MRI images were associated with longer survival of reirradiated patients. CONCLUSION: Reirradiation is a safe and effective approach for patients with DIPG. MRI-based radiomic models could be helpful in predicting survival after reirradiation.

Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

Diffuse Midline H3K27-Altered Gliomas in the Spinal Cord: A Systematic Review.

PURPOSE: To systematically review the clinical features, management, and outcomes of diffuse midline H3K27-altered gliomas of the spinal cord (DMG-SCs). METHODS: PubMed, Ovid EMBASE, Scopus, and Web of Science were searched from database inception to 23 September 2023 for histologically confirmed cases of DMG-SC. Patient demographics, tumor characteristics, management information, and survival outcomes were extracted and analyzed. RESULTS: A total of 279 patients from 39 studies were collected. Patients were mostly male (61%), with an average age of 32 years. Patients were treated with surgery, radiotherapy, and chemotherapy combined (31%) or surgery only (24%), and extent of resection was most often subtotal (38%). Temozolomide was the most common chemotherapeutic agent (81%). Radiation therapy was delivered with mean dose of 47 Gy in 23 fractions. At mean follow-up time of 21 months, 13% of patients were alive. Average median overall survival was 24 months (range of 13 to 40 months) with a median progression-free survival of 14 months. Historical WHO grades of 2 or 3 appeared to exhibit a longer average median overall survival time than that of grade 4 DMG-SCs (32 vs. 23 months, p = 0.009). CONCLUSIONS: Outcomes for DMG-SCs are poor overall but appear to be favorable compared to intracranial DMGs. Despite the recent WHO 2021 grade 4 classification for all DMGs, given the differences in overall survival reported based on historical grading systems, future studies on DMG-SCs are needed to further define if DMG-SCs may represent a heterogeneous group of tumors with different prognoses.

Prognostic factors analysis of diffuse midline glioma.

PURPOSE: This study retrospectively analyzes cases of diffuse midline glioma treated with radiotherapy, with the aim of investigating the prognosis of the tumor and its influencing factors. METHODS: From January 2018 to November 2022, we treated 64 patients who were pathologically diagnosed with diffuse midline glioma. Among them, 41 underwent surgical resection, and 23 underwent biopsy procedures. All patients received postoperative radiotherapy. We followed up with the patients to determine the overall survival rate and conducted univariate and multivariate analyses on relevant indicators. RESULTS: The median survival time for the entire patient group was 33.3 months, with overall survival rates of 92.9%, 75.4%, and 45.0% at 1 year, 2 years, and 3 years, respectively. Univariate and multivariate analyses indicated that older patients had a better prognosis. CONCLUSION: Patient age is an independent prognostic factor for patients with diffuse midline glioma undergoing radiation therapy.

The role of adjuvant chemotherapy in patients with H3K27 altered diffuse midline gliomas: a multicentric retrospective study.

PURPOSE: Adult Diffuse midline glioma (DMG) is a very rare disease. DMGs are currently treated with radiotherapy and chemotherapy even if only a few retrospective studies assessed the impact on overall survival (OS) of these approaches. METHODS: We carried out an Italian multicentric retrospective study of adult patients with H3K27-altered DMG to assess the effective role of systemic therapy in the treatment landscape of this rare tumor type. RESULTS: We evaluated 49 patients from 6 Institutions. The median age was 37.3 years (range 20.1-68.3). Most patients received biopsy as primary approach (n = 30, 61.2%) and radiation therapy after surgery (n = 39, 79.6%). 25 (51.0%) of patients received concurrent chemotherapy and 26 (53.1%) patients received adjuvant temozolomide. In univariate analysis, concurrent chemotherapy did not result in OS improvement while adjuvant temozolomide was associated with longer OS (21.2 vs. 9.0 months, HR 0.14, 0.05-0.41, p < 0.001). Multivariate analysis confirmed the role of adjuvant chemotherapy (HR 0.1, 95%CI: 0.03-0.34, p = 0.003). In patients who progressed after radiation and/or chemotherapy the administration of a second-line systemic treatment had a significantly favorable impact on survival (8.0 vs. 3.2 months, HR 0.2, 95%CI 0.1-0.65, p = 0.004). CONCLUSION: In our series, adjuvant treatment after radiotherapy can be useful in improving OS of patients with H3K27-altered DMG. When feasible another systemic treatment after treatment progression could be proposed.

Characteristics of H3K27M-mutant diffuse gliomas with a non-midline location.

PURPOSE: Diffuse midline gliomas (DMG) with H3K27 alterations (H3K27M-DMG) are a highly aggressive form of brain cancer. In rare cases, H3K27 mutations have been observed in diffuse non-midline gliomas (DNMG). It is currently unclear how these tumors should be classified. Herein, we analyze the characteristics of DNMG with H3K27M mutations. METHODS: We reviewed the clinical, radiological and histological characteristics of all patients with an H3K27M mutated diffuse glioma diagnosed in our institution, between 2016 and 2023, to identify cases with a non-midline location. We then performed a molecular characterization (DNA methylation profiling, whole genome and transcriptome sequencing or targeted sequencing) of patients with an H3K27M-mutant DNMG and reviewed previously reported cases. RESULTS: Among 51 patients (18 children and 33 adults) diagnosed with an H3K27M diffuse glioma, we identified two patients (4%) who had a non-midline location. Including our two patients, 39 patients were reported in the literature with an H3K27M-mutant DNMG. Tumors were most frequently located in the temporal lobe (48%), affected adolescents and adults, and were associated with a poor outcome (median overall survival was 10.3 months (0.1-84)). Median age at diagnosis was 19.1 years. Tumors frequently harbored TP53 mutations (74%), ATRX mutations (71%) and PDGFRA mutations or amplifications (44%). In DNA methylation analysis, H3K27M-mutant DNMG clustered within or close to the reference group of H3K27M-mutant DMG. Compared to their midline counterpart, non-midline gliomas with H3K27M mutations seemed more frequently associated with PDGFRA alterations. CONCLUSION: DNMG with H3K27M mutations share many similarities with their midline counterpart, suggesting that they correspond to a rare anatomical presentation of these tumors. This is of paramount importance, as they may benefit from new therapeutic approaches such as ONC201.

Single-cell RNA sequencing of anaplastic ependymoma and H3K27M-mutant diffuse midline glioma.

BACKGROUND: Anaplastic ependymoma and H3K27M-mutant diffuse midline glioma are two common subtypes of brain tumors with poor long-term prognosis. The present study analyzed and compared the differences in cell types between two tumors by single-cell RNA sequencing (scRNA-seq) technology. METHODS: ScRNA-seq was performed to profile cells from cancer tissue from anaplastic ependymoma patient and H3K27M-mutant diffuse midline glioma patient. Cell clustering, marker gene identification, cell type annotation, copy number variation analysis and function analysis of differentially expressed genes were then performed. RESULTS: A total of 11,219 cells were obtained from anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and these cells categorized into 12 distinct clusters. Each cell cluster could be characterized with specific cell markers to indicate cellular heterogeneity. Five cell types were annotated in each sample, including astrocyte, oligodendrocytes, microglial cell, neural progenitor cell and immune cell. The cluster types and proportion of cell types were not consistent between the two brain tumors. Functional analyses suggest that these cell clusters are involved in tumor-associated pathways, with slight differences in the cells of origin between the two tumors. In addition, cell communication analysis showed that the NRG3-ERBB4 pair is a key Ligand-receptor pair for anaplastic ependymoma, while in H3K27M-mutant diffuse midline glioma it is the PTN-PTPRZ1 pair that establishes contact with other cells. CONCLUSION: There was intratumor heterogeneity in anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and that the subtype differences may be due to differences in the origin of the cells.

Identification of prognostic imaging biomarkers in H3 K27-altered diffuse midline gliomas in adults: impact of tumor oxygenation imaging biomarkers on survival.

PURPOSE: To investigate prognostic markers for H3 K27-altered diffuse midline gliomas (DMGs) in adults with clinical, qualitative and quantitative imaging phenotypes, including tumor oxygenation characteristics. METHODS: Retrospective chart and imaging reviews were conducted on 32 adults with H3 K27-altered DMGs between 2017 and 2023. Clinical and qualitative imaging characteristics were analyzed. Quantitative imaging assessment was performed from the tumor mask via automatic segmentation to calculate normalized cerebral blood volume (nCBV), capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), relative cerebral metabolic rate of oxygen (rCMRO2), and mean ADC values. Leptomeningeal metastases (LM) was diagnosed with imaging. Cox analyses were conducted to determine predictors of overall survival (OS) in entire patients and a subgroup of patients with contrast-enhancing (CE) tumor. RESULTS: The median patient age was 40.5 years (range 19.9-75.7), with an OS of 30.3 months (interquartile range 11.3-32.3). In entire patients, the presence of LM was the only independent predictor of OS (hazard ratio [HR] = 6.01, P = 0.009). In the subgroup of 23 (71.9%) patients with CE tumors, rCMRO2 of CE tumor (HR = 1.08, P = 0.019) and the presence of LM (HR = 5.92, P = 0.043) were independent predictors of OS. CONCLUSION: The presence of LM was independently associated with poor prognosis in adult patients with H3 K27-altered DMG. In patients with CE tumors, higher rCMRO2 of CE tumor, which may reflect higher metabolic activity in the tumor oxygenation microenvironment, may be a useful imaging biomarker to predict poor prognosis.

The landscape of current research on pediatric diffuse midline glioma: a quantitative analysis of shifts, leaders, and future avenues.

PURPOSE: Diffuse midline glioma (DMG) has seen a surge of research interest in recent years with the growth in knowledge of new avenues for potential treatments. However, no bibliometric review of the field has been conducted to visualize the current state of the field. Here, we use bibliometric mapping to visualize the knowledge structure, collaborations, and trends in the field. METHODS: A total of 1079 original and review articles from 1996 to 2023 on diffuse midline glioma were extracted from the Web of Science Core Collection on June 3, 2023. These files were analyzed with R and VOSviewer to construct bibliometric visualizations. RESULTS: Research interest in DMG has continued to grow, driven by publications of original research. Molecular characterization of DMG has been a key focus of recent literature, and terms relating to novel small molecules, mutations, immunotherapy, the blood-brain barrier, and liquid biopsy may be areas for future growth in the literature. Collaborating nations have generally been the North American and European nations, but other nations have begun to make their mark in the field. Leading and rising institutions and journals are described. CONCLUSION: Research in DMG may continue to focus on molecular characterization and new therapeutics based on this knowledge. Novel collaborations between rising nations and institutions in the field may aid in accelerating this research.

Coexistence of longitudinally extensive transverse myelitis and diffuse midline glioma in the brainstem in an adolescent boy with acute flaccid paralysis.

We present the case of a previously healthy 13-year-old boy who was admitted to the emergency department with acute flaccid paralysis. Magnetic resonance imaging revealed radiological evidence of longitudinally extensive transverse myelitis. Additionally, homogeneous T2 signal increase was observed in the pons and medulla oblongata, initially indicating brainstem encephalitis. Subsequent evaluations confirmed a coexistence of diffuse midline glioma (DMG) in the brain stem alongside acute transverse myelitis (ATM). Children with ATM generally have a more favorable prognosis than adults. However, despite the implementation of advanced treatment methods, the patient's quadriplegia did not improve and resulted in spinal cord sequela atrophy. DMG exhibits an aggressive growth pattern and lacks a known curative treatment. This case represents an exceedingly rare synchronous occurrence of aggressive conditions, underscoring the importance of raising awareness among physicians. Furthermore, we aim to discuss the radiologic differential diagnosis, as this is the first documented instance in the literature.

Brain stem tumors in children less than 3 months: Clinical and radiologic findings of a rare disease.

PURPOSE: Brain stem tumors in children < 3 months at diagnosis are extremely rare. Our aim is to study a retrospective cohort to improve the understanding of the disease course and guide patient management. METHODS: This is a multicenter retrospective analysis across the European Society for Pediatric Oncology SIOP-E HGG/DIPG Working Group linked centers, including patients with a brainstem tumor diagnosed between 2009 and 2020 and aged < 3 months at diagnosis. Clinical data were collected, and imaging characteristics were analyzed blindly and independently by two neuroradiologists. RESULTS: Five cases were identified. No patient received any therapy. The epicenter of two tumors was in the medulla oblongata alone and in the medulla oblongata and the pons in three. For patients with tumor in equal parts in the medulla oblongata and the pons (n = 3), the extension at diagnosis involved the spinal cord; for the two patients with the tumor epicenter in the medulla oblongata alone (n = 2), the extension at diagnosis included the pons (n = 2) and the spinal cord (n = 1). Biopsy was performed in one patient identifying a pilocytic astrocytoma. Two patients died. In one patient, autopsy revealed a high-grade glioma (case 3). Three survivors showed either spontaneous tumor regression (n = 2) or stable disease (n = 1). Survivors were followed up for 10, 7, and 0.6 years, respectively. One case had the typical imaging characteristics of a dorsal exophytic low-grade glioma. CONCLUSIONS: No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy may provide useful information regarding the patient management.

Biopsy of diffuse midline glioma is safe and impacts targeted therapy: a systematic review and meta-analysis.

PURPOSE: To quantify the safety and utility of biopsy of pediatric diffuse midline glioma (DMG). METHODS: This study was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and Web of Science were queried for relevant articles from inception until June 2023. Two reviewers identified all articles that included diagnostic yield, morbidity, and mortality rates for pediatric DMG patients. Studies that did not present original data or were not in English or peer-reviewed were excluded. Meta-analysis was conducted in R using Freeman-Tukey or logit transformation and DerSimonian-Laird random-effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. A protocol for this review was not registered. RESULTS: We identified 381 patients from ten studies that met all criteria. DMG biopsy is safe overall (0% mortality, 95% CI: 0-0.6%; 11.0% morbidity, 95% CI: 4.8-18.9%) and has a high diagnostic yield (99.9%, 95% CI: 98.5-100%). The use of stereotactic biopsy is a significant moderator of morbidity (p = 0.0238). Molecular targets can be identified in approximately 53.4% of tumors (95% CI: 37.0-69.0%), although targeted therapies are only delivered in about 33.5% of all cases (95% CI: 24.4-44.1%). Heterogeneity was high for morbidity and identification of targets. The risk of bias was low for all studies. CONCLUSION: We conducted the first meta-analysis of DMG biopsy to show that it is safe, effective, and able to identify relevant molecular targets that impact targeted therapy.

Clinicohistoradiological and surgical outcome in diffuse midline glioma.

PURPOSE: Diffuse Midline Glioma (DMG) with H3K27M mutation is a rare and aggressive midline high grade glioma with a predominant astrocytic differentiation and K27M mutation in either H3F3A or HIST1H3B/C. This tumor is more common in children than in adults. The current study was aimed to determine clinicohistoradiological and surgical outcome of patients who have undergone surgery for DMG and study disease severity of patients with DMG. METHODS: This is an observational study in which 29 DMG patients were evaluated for clinicohistoradiological and surgical outcomes by assessing the pre and postoperative neurological status. RESULT: Survival duration was significantly high in patients with age > 18 years (p = 0.02). Patients who had undergone Radiation Therapy showed higher survival rate (p = 0.05) and the cases with low levels of Ki 67 index had improved post operative outcome (p = 0.002). CONCLUSION: DMG with H3K27M mutation in newly classified Central Nervous System tumor are WHO grade IV Tumors, comprising H3K27M mutation as molecular marker for diagnosis and related with a poor prognosis.

Distinct MRI characteristics of spinal cord diffuse midline glioma, H3 K27-altered in comparison to spinal cord glioma without H3 K27-alteration and demyelination disorder.

BACKGROUND: An applicable magnetic resonance imaging (MRI) biomarker for diffuse midline glioma (DMG), H3 K27-altered of the spinal cord is important for non-invasive diagnosis. PURPOSE: To evaluate the efficacy of conventional MRI (cMRI) in distinguishing between DMGs, H3 K27-altered, gliomas without H3 K27-alteration, and demyelinating lesions in the spinal cord. MATERIAL AND METHODS: Between January 2017 and February 2023, patients with pathology-confirmed spinal cord gliomas (including ependymomas) with definite H3 K27 status and demyelinating diseases diagnosed by recognized criteria were recruited as the training set for this retrospective study. Morphologic parameter assessment was performed by two neuroradiologists on T1-weighted, T2-weighted, and contrast-enhanced T1-weighted imaging. Variables with high inter- and intra-observer agreement were included in univariable correlation analysis and multivariable logistic regression. The performance of the final model was verified by internal and external testing sets. RESULTS: The training cohort included 21 patients with DMGs (13 men; mean age = 34.57 ± 13.489 years), 21 with wild-type gliomas (10 men; mean age = 46.76 ± 17.017 years), and 20 with demyelinating diseases (5 men; mean age = 49.50 ± 18.872 years). A significant difference was observed in MRI features, including cyst(s), hemorrhage, pial thickening with enhancement, and the maximum anteroposterior diameter of the spinal cord. The prediction model, integrating age, age2, and morphological characteristics, demonstrated good performance in the internal and external testing cohort (accuracy: 0.810 and 0.800, specificity: 0.810 and 0.720, sensitivity: 0.872 and 0.849, respectively). CONCLUSION: Based on cMRI, we developed a model with good performance for differentiating among DMGs, H3 K27-altered, wild-type glioma, and demyelinating lesions in the spinal cord.

Molecular insights and the role of 18F-FDG-PET/CT in the diagnosis of spinal gliomas.

BACKGROUND: In recent years, molecular findings on spinal gliomas have become increasingly important. This study aimed to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis of spinal glioma. METHODS: This study included patients diagnosed with spinal cord glioma who underwent 18F-FDG-PET examination at the Department of Neurosurgery, Nagoya University Hospital between January 2016 and November 2023. The gliomas were divided into two groups, high-grade and low-grade, based on pathological and molecular studies. The maximum standardized uptake values (SUVmax) of the tumors were quantified and subsequently represented using receiver operating characteristic (ROC) curves. RESULTS: Eighteen participants were included in this study. Of the participants, seven had high-grade glioma with an SUVmax of 6.76 ± 0.72, and eleven had low-grade glioma with an SUVmax of 4.02 ± 1.78, and a statistically significant difference between the two groups. The ROC curve delineated an SUVmax cutoff value of 5.650, with an area under the curve (AUC) of approximately 0.909. Based on the cutoff value, the results of the diagnostic performance rendered a sensitivity and negative predictive value of 1.0, whereas the specificity and positive predictive value were 0.909 and 0.875, respectively. CONCLUSIONS: The present study shows that 18F-FDG-PET exhibits a markedly sensitive and negative predictive value in the assessment of spinal gliomas. Additionally, these findings have potential implications for the qualitative assessment of spinal gliomas using 18F-FDG-PET/CT. This imaging modality may be useful for making timely treatment decisions in situations where a detailed diagnosis by molecular analysis is not possible.

11C-methionine PET imaging characteristics in children with diffuse intrinsic pontine gliomas and relationship to survival and H3 K27M mutation status.

PURPOSE: This study aimed to describe 11C-methionine (11C-MET) PET imaging characteristics in patients with paediatric diffuse intrinsic pontine glioma (DIPG) and correlate them with survival and H3 K27M mutation status. METHODS: We retrospectively analysed 98 children newly diagnosed with DIPG who underwent 11C-MET PET. PET imaging characteristics evaluated included uptake intensity, uniformity, metabolic tumour volume (MTV), and total lesion methionine uptake (TLMU). The maximum, mean, and peak of the tumour-to-background ratio (TBR), calculated as the corresponding standardised uptake values (SUV) divided by the mean reference value, were also recorded. The associations between the PET imaging characteristics and clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) and H3 K27M mutation status were assessed, respectively. RESULTS: In univariate analysis, imaging characteristics significantly associated with shorter PFS and OS included a higher uniformity grade, higher TBRs, larger MTV, and higher TLMU. In multivariate analysis, larger MTV at diagnosis, shorter symptom duration, and no treatment were significantly correlated with shorter PFS and OS. The PET imaging features were not correlated with H3 K27M mutation status. CONCLUSION: Although several imaging features were significantly associated with PFS and OS, only MTV, indicating the size of the active tumour, was identified as a strong independent prognostic factor.

Deep Learning for Noninvasive Assessment of H3 K27M Mutation Status in Diffuse Midline Gliomas Using MR Imaging.

BACKGROUND: Determination of H3 K27M mutation in diffuse midline glioma (DMG) is key for prognostic assessment and stratifying patient subgroups for clinical trials. MRI can noninvasively depict morphological and metabolic characteristics of H3 K27M mutant DMG. PURPOSE: This study aimed to develop a deep learning (DL) approach to noninvasively predict H3 K27M mutation in DMG using T2-weighted images. STUDY TYPE: Retrospective and prospective. POPULATION: For diffuse midline brain gliomas, 341 patients from Center-1 (27 ± 19 years, 184 males), 42 patients from Center-2 (33 ± 19 years, 27 males) and 35 patients (37 ± 18 years, 24 males). For diffuse spinal cord gliomas, 133 patients from Center-1 (30 ± 15 years, 80 males). FIELD STRENGTH/SEQUENCE: 5T and 3T, T2-weighted turbo spin echo imaging. ASSESSMENT: Conventional radiological features were independently reviewed by two neuroradiologists. H3 K27M status was determined by histopathological examination. The Dice coefficient was used to evaluate segmentation performance. Classification performance was evaluated using accuracy, sensitivity, specificity, and area under the curve. STATISTICAL TESTS: Pearson's Chi-squared test, Fisher's exact test, two-sample Student's t-test and Mann-Whitney U test. A two-sided P value <0.05 was considered statistically significant. RESULTS: In the testing cohort, Dice coefficients of tumor segmentation using DL were 0.87 for diffuse midline brain and 0.81 for spinal cord gliomas. In the internal prospective testing dataset, the predictive accuracies, sensitivities, and specificities of H3 K27M mutation status were 92.1%, 98.2%, 82.9% in diffuse midline brain gliomas and 85.4%, 88.9%, 82.6% in spinal cord gliomas. Furthermore, this study showed that the performance generalizes to external institutions, with predictive accuracies of 85.7%-90.5%, sensitivities of 90.9%-96.0%, and specificities of 82.4%-83.3%. DATA CONCLUSION: In this study, an automatic DL framework was developed and validated for accurately predicting H3 K27M mutation using T2-weighted images, which could contribute to the noninvasive determination of H3 K27M status for clinical decision-making. EVIDENCE LEVEL: 2 Technical Efficacy: Stage 2.