MR Imaging of Pediatric Neuroblastoma: Is Gadolinium Enhancement Necessary for Evaluation of Image-Defined-Risk Factors?

Background: Pre-treatment stratification and outcomes of neuroblastoma patients often depend on the assessment of image-defined risk factors (IDRFs) on MR Imaging, usually using Gadolinium-contrast materials which are cautioned in pediatrics. We aimed to address whether gadolinium contrast-enhanced sequences are necessary to identify the presence/absence of IDRFs. Methods: Patients with neuroblastoma with MR imaging were retrospectively identified from 2005 to 2021. Ninety confirmed IDRFs were evaluated in 23 patients. Corresponding MR studies were anonymized, randomized, and independently evaluated by 3 fellowship-trained pediatric radiologists. Each radiologist assessed the studies twice. At the first reading, all enhanced sequences were omitted, while in the second reading, the full study with enhanced sequences were included. Consensus reading was obtained among readers. Inter- and intra-rater agreements using Kappa statistics (κ) as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of non-enhanced MR in assessing IDRFs with respect to enhanced MR were calculated. Results: There were substantial (ĸ: 0.64-0.73) intra-reader agreements, and moderate to substantial (ĸ: 0.57-0.62) inter-reader agreements among radiologists in identifying IDRFs using non-enhanced MR. Non-enhanced MR had a sensitivity of 87.8% (95% CI [79-94]), specificity of 93% (89-96), PPV of 82.3 (73-89), NPV of 95.4 (92-98), and accuracy of 91.6 (88-94) in identifying IDRFs. However, 5/23 patients (21.7%) had a change in staging with the inclusion of contrast sequences. Conclusion: Although contrast sequences have a role in IDRF assessment, the majority can be adequately assessed on MR without gadolinium-contrast enhancement. Validation in a larger cohort is an important next step.

Systematic review of diffuse hemispheric glioma, H3 G34-mutant: Outcomes and associated clinical factors.

Background: A comprehensive review and description of the clinical features that impact prognosis for patients with diffuse hemispheric glioma, H3 G34-mutant (G34-DHG) is needed. Understanding survival and prognostic features is paramount for clinical advancements and patient care. Methods: PubMed, Embase, and Google Scholar were searched for English articles published between January 1, 2012 and June 30, 2021. Eligible studies included patient(s) of any age diagnosed with an H3 G34-mutant brain tumor with at least one measure of survival or progression. Patient-level data were pooled for analyses. This study was prospectively registered in PROSPERO (CRD42021267764) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Results: Twenty-seven studies met the criteria with a total of 135 patients included. Median age at diagnosis was 15.8 years (interquartile range [IQR]: 13.3-22.0) with 90% having localized disease. Co-occurring alterations included ATRX mutation in 93%, TP53 mutation in 88%, and MGMT promoter methylation in 70%. Median time-to-progression was 10.0 months (IQR: 6.0-18.0) and median overall survival was 17.3 months (95% CI: 15.0 to 22.9). The median time from progression to death was 5.0 months (IQR: 3.0-11.7). Factors associated with survival duration were age, as patients ≥18 y/o demonstrated longer survival (hazard ratio [HR] =2.05, 95% CI: 1.16 to 3.62), and degree of upfront resection, as near or gross-total resection demonstrated longer survival compared to those with less than near-total resection (HR = 3.75, 95% CI: 2.11 to 6.62). Conclusion: This systematic review highlights available clinical data for G34-DHG demonstrating poor outcomes and important prognostic features, while serving as a baseline for future research and clinical trials.

Response assessment in paediatric high-grade glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Response criteria for paediatric high-grade glioma vary historically and across different cooperative groups. The Response Assessment in Neuro-Oncology working group developed response criteria for adult high-grade glioma, but these were not created to meet the unique challenges in children with the disease. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop response assessment criteria for paediatric high-grade glioma. Current practice and literature were reviewed to identify major challenges in assessing the response of paediatric high-grade gliomas to various treatments. For areas in which scientific investigation was scarce, consensus was reached through an iterative process. RAPNO response assessment recommendations include the use of MRI of the brain and the spine, assessment of clinical status, and the use of corticosteroids or antiangiogenics. Imaging standards for brain and spine are defined. Compared with the recommendations for the management of adult high-grade glioma, for paediatrics there is inclusion of diffusion-weighted imaging and a higher reliance on T2-weighted fluid-attenuated inversion recovery. Consensus recommendations and response definitions have been established and, similar to other RAPNO recommendations, prospective validation in clinical trials is warranted.

HR-pQCT imaging in children, adolescents and young adults: Systematic review and subgroup meta-analysis of normative data.

We aimed to investigate the methodologies on image acquisition of normative data of high-resolution peripheral quantitative computed tomography (HR-pQCT) in children, adolescents and/or young adults (up to 25 years) and to determine their normative data based on available literature. A literature search was conducted in MEDLINE, EMBASE and Web of Science from 1947 to July 2019. Quality of articles was assessed using Standards for Reporting of Diagnostic Accuracy (STARD) scoring system and Modified Newcastle-Ottawa scale (NOS). Articles which fitted the following criteria were combined to meta-analysis: age range (15 to 22.6 years), references at tibia (22.5mm) and/or radius (9.0 to 9.5mm). Eight articles were ultimately included in the systematic review and 4 of them that filled the criteria were summarised in meta-analysis. The results of random effects model of HR-pQCT parameters of the 4 articles were as follows: 1)Radius: bone volume fraction (BT/BV) [estimate 0.17:0.1229(lower)-0.2115 (upper); trabecular number (Tb_N):2.08(2.03-2.12); trabecular thickness (Tb.Th):0.07 (0.07-0.0.08); trabecular separation (Tb.Sp):0.41 (0.38-0.42); cortical thickness (Ct.Th):0.85 (0.76-0.94); cortical porosity (Ct.Po):1.53 (0.63-2.44); total area (Tt.Ar):263.66(-385.3-912.6); total bone density (Tt-vBMD):280.5 (73.1-487.7); Trabecular density (Tb-vBMD):223.6 (47.1-400.09), and cortical density (CT.vBMD):765.9 (389.1-1142.8). 2)Tibia: BT/BV:0.18 (0.17-0.19); Tb_N:2.02 (1.83-2.2); Tb.Th:0.08 (0.80-0.09); Tb.Sp:0.40(0.36-0.44); Ct.Th:1.32(1.26-1.38); Ct.Po:3.15 (1.1-5.2); Tt.Ar:693.1(150.2-1235.8); Tt-vBMD:343.76 (335.5-352.1); Tb-vBMD:223.6 (213.37 (193.5-233.2), and CT.vBMD:894.3 (857.6-931.1). There is overall 'fair' evidence on reporting of results of normative data of HR-pQCT parameters in children, adolescents and/or young adults. However, data are scarce pointing out to the urgent need for standardization of acquisition parameters and guidelines on the use of HR-PQCT in these populations.

320-row CT transcatheter aortic valve replacement planning with a single reduced contrast media bolus injection.

OBJECTIVE: To reduce the iodine load required for CT Transcatheter Aortic Valve Replacement (TAVR) planning on a 320-row scanner by acquiring the two CT TAVR steps (ECG-gated aortic root CTA and non-gated aorto-ilio-femoral CTA) within a single contrast media bolus injection. METHODS: 50 consecutive patients (82.6±6.9 years; 56% female) were prospectively enrolled and underwent a TAVR planning using a 320-row CT, with ECG-gated aortic root CTA immediately followed by a non-gated aorto-iliac acquisition, all within a single bolus of 40-70mL of Iohexol 350mgI/mL. The Iodine load, image quality, SNR, CNR and radiation dose were compared using a Mann-Whitney test to that of 24 consecutive patients (84.3±4.8 years, 58% female) previously imaged on a 64-row scanner with a conventional two-step protocol. RESULTS: Iodine load was reduced by 44%. All examinations were of diagnostic quality, with improvement of the aortic root CTA image quality (4.9±0.3 versus 4.6±0.5, p<0.01) and a non-significant decrease of the aorto-iliac CTA image quality (4.7±0.6 versus 4.9±0.3, p = 0.07). SNR and CNR were significantly improved in the aortic root CTA (14.0±5.3 and 10.4±4.5 versus 10.3±4.2 and 6.8±3.3, p<0.01 for both) and non-significantly higher in the aorto-iliac CTA (16.5±8.0 and 14.1±7.9 versus 14.7±5.5 and 12.5±5.0, p = 0.42 and p = 0.66). Total radiation dose was reduced by 32%. CONCLUSION: 320-row CT scanner enables a 44% reduction of iodine load in TAVR planning, while maintaining excellent aorto-ilio-femoral arterial enhancement and lowering radiation dose.

Arachnoid cysts with spontaneous intracystic hemorrhage and associated subdural hematoma: Report of management and follow-up of 2 cases.

Arachnoid cysts are one of the most frequently encountered intracranial space-occupying lesions in daily neurosurgery and neuroradiology practice. Majority of arachnoid cysts, particularly those of smaller sizes, have a benign uneventful lifetime course. Certain symptoms may indicate serious complications related to underlying arachnoid cysts. Hemorrhage is one of the most fearsome complications of arachnoid cysts and almost all reported cases in the literature have undergone surgical correction. In this study, we aimed to present clinical and radiologic follow-up findings in two adult cases of intracranial arachnoid cyst with spontaneous intracystic hemorrhage and associated subdural hematoma, one of which was successfully treated conservatively. In addition, we broadly summarized and discussed pertinent studies in the English literature.

Traumatic midline subarachnoid hemorrhage on initial computed tomography as a marker of severe diffuse axonal injury.

OBJECTIVEThe objective of this study was to test the hypothesis that midline (interhemispheric or perimesencephalic) traumatic subarachnoid hemorrhage (tSAH) on initial CT may implicate the same shearing mechanism that underlies severe diffuse axonal injury (DAI).METHODSThe authors enrolled 270 consecutive patients (mean age [± SD] 43 ± 23.3 years) with a history of head trauma who had undergone initial CT within 24 hours and brain MRI within 30 days. Six initial CT findings, including intraventricular hemorrhage (IVH) and tSAH, were used as candidate predictors of DAI. The presence of tSAH was determined at the cerebral convexities, sylvian fissures, sylvian vallecula, cerebellar folia, interhemispheric fissure, and perimesencephalic cisterns. Following MRI, patients were divided into negative and positive DAI groups, and were assigned to a DAI stage: 1) stage 0, negative DAI; 2) stage 1, DAI in lobar white matter or cerebellum; 3) stage 2, DAI involving the corpus callosum; and 4) stage 3, DAI involving the brainstem. Glasgow Outcome Scale-Extended (GOSE) scores were obtained in 232 patients.RESULTSOf 270 patients, 77 (28.5%) had DAI; tSAH and IVH were independently associated with DAI (p < 0.05). Of tSAH locations, midline tSAH was independently associated with both overall DAI and DAI stage 2 or 3 (severe DAI; p < 0.05). The midline tSAH on initial CT had sensitivity of 60.8%, specificity of 81.7%, and positive and negative predictive values of 43.7% and 89.9%, respectively, for severe DAI. When adjusted for admission Glasgow Coma Score, the midline tSAH independently predicted poor GOSE score at both hospital discharge and after 6 months.CONCLUSIONSMidline tSAH could implicate the same shearing mechanism that underlies severe DAI, for which midline tSAH on initial CT is a probable surrogate.

Differential patterns of metastatic dissemination across medulloblastoma subgroups.

OBJECTIVE Metastatic dissemination is a major treatment challenge and cause of death in patients with medulloblastoma. However, the influence of molecular biology on the pattern of metastatic dissemination at diagnosis is not known. In this study, the authors sought to define the location, pattern, and imaging characteristics of medulloblastoma metastases across subgroups at diagnosis. METHODS A consecutive cohort of patients with metastatic medulloblastoma at The Hospital for Sick Children and the University Hospital Motol, who underwent up-front MRI of the craniospinal axis, was assembled and allocated to subgroups using NanoString limited gene-expression profiling. Radiological characteristics (including location, morphology, size, diffusion restriction, and contrast enhancement) were discerned through a retrospective review. RESULTS Forty metastatic medulloblastomas were identified with up-front neuroimaging of the craniospinal axis: 5 sonic hedgehog (SHH), 16 Group 3, and 19 Group 4 metastases. Significant subgroup-specific differences were observed, particularly with respect to tumor location, size, and morphology. Group 3 metastases were most frequently laminar compared with a more nodular pattern in Group 4 (14 of 16 in Group 3 vs 8 of 19 in Group 4; p = 0.0004). Laminar metastases were not observed in patients with SHH medulloblastoma. Suprasellar metastases are highly specific to Group 4 (p = 0.016). Two of the 5 SHH cases had multifocal lesions in the cerebellum, raising the possibility that these were in fact synchronous primary tumors and not true metastases. A minority of patients with Group 4 metastases harbored metastatic deposits that did not enhance on MRI after contrast administration, often in patients whose primary tumor did not enhance. CONCLUSIONS The location, morphology, and imaging characteristics of metastatic medulloblastoma differ across molecular subgroups, with implications for diagnosis and management. This suggests that the biology of leptomeningeal dissemination differs among medulloblastoma subgroups.

Canadian CT head rule and New Orleans Criteria in mild traumatic brain injury: comparison at a tertiary referral hospital in Japan.

We compared Canadian computed tomography (CT) head rule (CCHR) and New Orleans Criteria (NOC) in predicting important CT findings in patients with mild traumatic brain injury (TBI). We included 142 consecutive patients with mild TBI [Glasgow coma scale (GCS) 13-15] who showed at least one of the risk factors stated in the CCHR or the NOC. We introduced two scores: a Canadian from the CCHR and a New Orleans from the NOC. A patient's score represented a sum of the number of positive items. We examined the relationship between scores or items and the presence of important CT findings. Only the Canadian was significantly associated with important CT findings in multivariate analyses and showed higher area under the receiver operating characteristic curve (AUC) either in all 142 patients (GCS 13-15: P = 0.0130; AUC = 0.69) or in the 67 with a GCS = 15 (P = 0.0128, AUC = 0.73). Of items, ">60 years" or "≥65 years" included in either guideline was the strongest predictor of important CT finding, followed by "GCS < 15 after 2 h" included only in the CCHR. In a tertiary referral hospital in Japan, CCHR had higher performance than the NOC in predicting important CT findings.

Intraventricular hemorrhage on initial computed tomography as marker of diffuse axonal injury after traumatic brain injury.

Intraventricular hemorrhage (IVH) on initial computed tomography (CT) was reported to predict lesions of diffuse axonal injury (DAI) in the corpus callosum (CC) on subsequent magnetic resonance imaging (MRI). We aimed to examine the relationship between initial CT findings and DAI lesions detected on MRI as well as the relationship between the severity of IVH (IVH score) and severity of DAI (DAI staging). A consecutive 140 patients with traumatic brain injury (TBI) who underwent MRI within 30 days after onset were revisited. We reviewed their initial CT for the following six findings: Status of basal cistern, status of mid-line shift, epidural hematoma, IVH, subarachnoid hemorrhage, and volume of hemorrhagic mass and IVH score were assigned in each patient. Based on MRI findings, patients were divided into DAI and non-DAI groups and were assigned a DAI staging. Then, to confirm that the IVH on initial CT predicts DAI lesions on MRI, we used multi-variate analysis of the six CT findings, including IVH, and examined the relationship between IVH score and DAI staging. The IVH detected on CT was the only predictor of DAI (p=0.0139). The IVH score and DAI staging showed significant positive correlation (p<0.0003). IVH score in DAI stage 3 (with DAI involving the brain stem; p=0.0025) or stage 2 (with DAI involving CC; p=0.0042) was significantly higher than that of DAI stage 0 (no DAI lesions). In conclusion, IVH on initial CT is the only marker of DAI on subsequent MRI, specifically severe DAI (stage 2 or 3).

Early CT findings to predict early death in patients with traumatic brain injury: Marshall and Rotterdam CT scoring systems compared in the major academic tertiary care hospital in northeastern Japan.

RATIONALE AND OBJECTIVES: Computed tomography (CT) plays a crucial role in early assessment of patients with traumatic brain injury (TBI). Marshall and Rotterdam are the mostly used scoring systems, in which CT findings are grouped differently. We sought to determine the scoring system and initial CT findings predicting the death at hospital discharge (early death) in patients with TBI. MATERIALS AND METHODS: We included 245 consecutive adult patients with mild-to-severe TBI. Their initial CT and status at hospital discharge (dead or alive) were reviewed, and both CT scores were calculated. We examined whether each score was related to early death; compared the two scoring systems' performance in predicting early death, and identified the CT findings that are independent predictors of early death. RESULTS: More deaths occurred among patients with higher Marshall and Rotterdam scores (both P < .05, Mann-Whitney U test). The areas under the receiver operating characteristic curve (AUCs) indicated that both scoring systems had similarly good discriminative power in predicting early death (Marshall, AUC = 0. 85 vs. Rotterdam, AUC = 0.85). Basal cistern absence (odds ratio [OR] = 771.5, P < .0001), positive midline shift (OR = 56.2, P = .0011), hemorrhagic mass volume ≥25 mL (OR = 12.9, P = .0065), and intraventricular or subarachnoid hemorrhage (OR = 3.8, P = .0395) were independent predictors of early death. CONCLUSIONS: Both Marshall and Rotterdam scoring systems can be used to predict early death in patients with TBI. The performance of the Marshall score is at least equal to that of the Rotterdam score. Thus, although older, the Marshall score remains useful in predicting patients' prognosis.