Standardized evaluation of the extent of resection in glioblastoma with automated early post-operative segmentation.

Standard treatment of patients with glioblastoma includes surgical resection of the tumor. The extent of resection (EOR) achieved during surgery significantly impacts prognosis and is used to stratify patients in clinical trials. In this study, we developed a U-Net-based deep-learning model to segment contrast-enhancing tumor on post-operative MRI exams taken within 72 h of resection surgery and used these segmentations to classify the EOR as either maximal or submaximal. The model was trained on 122 multiparametric MRI scans from our institution and achieved a mean Dice score of 0.52 ± 0.03 on an external dataset (n = 248), a performance -on par with the interrater agreement between expert annotators as reported in literature. We obtained an EOR classification precision/recall of 0.72/0.78 on the internal test dataset (n = 462) and 0.90/0.87 on the external dataset. Furthermore, Kaplan-Meier curves were used to compare the overall survival between patients with maximal and submaximal resection in the internal test dataset, as determined by either clinicians or the model. There was no significant difference between the survival predictions using the model's and clinical EOR classification. We find that the proposed segmentation model is capable of reliably classifying the EOR of glioblastoma tumors on early post-operative MRI scans. Moreover, we show that stratification of patients based on the model's predictions offers at least the same prognostic value as when done by clinicians.

The Current Diagnostic Performance of MRI-Based Radiomics for Glioma Grading: A Meta-Analysis.

BACKGROUND: Multiple radiomics models have been proposed for grading glioma using different algorithms, features, and sequences of magnetic resonance imaging. The research seeks to assess the present overall performance of radiomics for grading glioma. METHODS: A systematic literature review of the databases Ovid MEDLINE PubMed, and Ovid EMBASE for publications published on radiomics for glioma grading between 2012 and 2023 was performed. The systematic review was carried out following the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. RESULTS: In the meta-analysis, a total of 7654 patients from 40 articles, were assessed. R-package mada was used for modeling the joint estimates of specificity (SPE) and sensitivity (SEN). Pooled event rates across studies were performed with a random-effects meta-analysis. The heterogeneity of SPE and SEN were based on the χ2 test. Overall values for SPE and SEN in the differentiation between high-grade gliomas (HGGs) and low-grade gliomas (LGGs) were 84% and 91%, respectively. With regards to the discrimination between World Health Organization (WHO) grade 4 and WHO grade 3, the overall SPE was 81% and the SEN was 89%. The modern non-linear classifiers showed a better trend, whereas textural features tend to be the best-performing (29%) and the most used. CONCLUSIONS: Our findings confirm that present radiomics' diagnostic performance for glioma grading is superior in terms of SEN and SPE for the HGGs vs. LGGs discrimination task when compared to the WHO grade 4 vs. 3 task.

The impact of cancer patient pathway on timing of radiotherapy and survival: a cohort study in glioblastoma patients.

PURPOSE: Glioblastoma (GBM) is an aggressive brain tumor in which primary therapy is standardized and consists of surgery, radiotherapy (RT), and chemotherapy. However, the optimal time from surgery to start of RT is unknown. A high-grade glioma cancer patient pathway (CPP) was implemented in Norway in 2015 to avoid non-medical delays and regional disparity, and to optimize information flow to patients. This study investigated how CPP affected time to RT after surgery and overall survival. METHODS: This study included consecutive GBM patients diagnosed in South-Eastern Norway Regional Health Authority from 2006 to 2019 and treated with RT. The pre CPP implementation group constituted patients diagnosed 2006-2014, and the post CPP implementation group constituted patients diagnosed 2016-2019. We evaluated timing of RT and survival in relation to CPP implementation. RESULTS: A total of 1212 patients with GBM were included. CPP implementation was associated with significantly better outcomes (p < 0.001). Median overall survival was 12.9 months. The odds of receiving RT within four weeks after surgery were significantly higher post CPP implementation (p < 0.001). We found no difference in survival dependent on timing of RT below 4, 4-6 or more than 6 weeks (p = 0.349). Prognostic factors for better outcomes in adjusted analyses were female sex (p = 0.005), younger age (p < 0.001), solitary tumors (p = 0.008), gross total resection (p < 0.001), and higher RT dose (p < 0.001). CONCLUSION: CPP implementation significantly reduced time to start of postoperative RT. Survival was significantly longer in the period after the CPP implementation, however, timing of postoperative RT relative to time of surgery did not impact survival.

Consensus paper on the assessment of adult patients with traumatic brain injury with Glasgow Coma Scale 13-15 at the emergency department: A multidisciplinary overview.

Traumatic brain injury (TBI) is a common reason for presenting to emergency departments (EDs). The assessment of these patients is frequently hampered by various confounders, and diagnostics is still often based on nonspecific clinical signs. Throughout Europe, there is wide variation in clinical practices, including the follow-up of those discharged from the ED. The objective is to present a practical recommendation for the assessment of adult patients with an acute TBI, focusing on milder cases not requiring in-hospital care. The aim is to advise on and harmonize practices for European settings. A multiprofessional expert panel, giving consensus recommendations based on recent scientific literature and clinical practices, is employed. The focus is on patients with a preserved consciousness (Glasgow Coma Scale 13-15) not requiring in-hospital care after ED assessment. The main results of this paper contain practical, clinically usable recommendations for acute clinical assessment, decision-making on acute head computerized tomography (CT), use of biomarkers, discharge options, and needs for follow-up, as well as a discussion of the main features and risk factors for prolonged recovery. In conclusion, this consensus paper provides a practical stepwise approach for the clinical assessment of patients with an acute TBI at the ED. Recommendations are given for the performance of acute head CT, use of brain biomarkers and disposition after ED care including careful patient information and organization of follow-up for those discharged.

A woman in her forties with ear pain. / En kvinne i 40-årene med smerter i øret.

Background: A woman in her forties developed intermittent pain in her ear and pharynx which worsened when talking and swallowing. Multidisciplinary approach confirmed a rare diagnosis. Case presentation: The patient reported left-sided ear fullness, followed by otalgia and burning pain in the palate. Numbness in the palate and nasal cavity, and soreness upon palpation of the external ear canal were noted upon examination. Magnetic resonance imaging (MRI) with contrast showed a vessel located in close proximity to the glossopharyngeal nerve on the left side. A diagnosis of glossopharyngeal neuralgia was made, and the patient was treated with antiepileptic medications without substantial effect. Microvascular decompression of the glossopharyngeal nerve was therefore performed. A large vein located along the glossopharyngeal nerve was separated and fixated away from the nerve. The patient reported pain alleviation after the operation, which has continued to improve on follow-ups. Interpretation: Glossopharyngeal neuralgia is a rare condition characterised by intermittent, unilateral pain in the base of the tongue, oropharynx, and/or angle of the mandible which radiates to the ipsilateral ear. The condition should be treated medically, but open surgical treatment should be considered in refractory cases. Early diagnosis and treatment are essential.

Incidence and outcome of pseudoprogression after radiation therapy in glioblastoma patients: A cohort study.

Background: Differentiating post-radiation MRI changes from progressive disease (PD) in glioblastoma (GBM) patients represents a major challenge. The clinical problem is two-sided; avoid termination of effective therapy in case of pseudoprogression (PsP) and continuation of ineffective therapy in case of PD. We retrospectively assessed the incidence, management, and prognostic impact of PsP and analyzed factors associated with PsP in a GBM patient cohort. Methods: Consecutive GBM patients diagnosed in the South-Eastern Norway Health Region from 2015 to 2018 who had received RT and follow-up MRI were included. Tumor, patient, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at 3 and 6 months post-radiation using Response Assessment in Neuro-Oncology criteria. Results: A total of 284 patients were included in the study. PsP incidence 3 and 6 months post-radiation was 19.4% and 7.0%, respectively. In adjusted analyses, methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter and the absence of neurological deterioration were associated with PsP at both 3 (p < .001 and p = .029, respectively) and 6 months (p = .045 and p = .034, respectively) post-radiation. For patients retrospectively assessed as PD 3 months post-radiation, there was no survival benefit of treatment change (p = .838). Conclusions: PsP incidence was similar to previous reports. In addition to the previously described correlation of methylated MGMT promoter with PsP, we also found that absence of neurological deterioration significantly correlated with PsP. Continuation of temozolomide courses did not seem to compromise survival for patients with PD at 3 months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings.

Diagnostic accuracy of anti-3-[18F]-FACBC PET/MRI in gliomas.

PURPOSE: The primary aim was to evaluate whether anti-3-[18F]FACBC PET combined with conventional MRI correlated better with histomolecular diagnosis (reference standard) than MRI alone in glioma diagnostics. The ability of anti-3-[18F]FACBC to differentiate between molecular and histopathological entities in gliomas was also evaluated. METHODS: In this prospective study, patients with suspected primary or recurrent gliomas were recruited from two sites in Norway and examined with PET/MRI prior to surgery. Anti-3-[18F]FACBC uptake (TBRpeak) was compared to histomolecular features in 36 patients. PET results were then added to clinical MRI readings (performed by two neuroradiologists, blinded for histomolecular results and PET data) to assess the predicted tumor characteristics with and without PET. RESULTS: Histomolecular analyses revealed two CNS WHO grade 1, nine grade 2, eight grade 3, and 17 grade 4 gliomas. All tumors were visible on MRI FLAIR. The sensitivity of contrast-enhanced MRI and anti-3-[18F]FACBC PET was 61% (95%CI [45, 77]) and 72% (95%CI [58, 87]), respectively, in the detection of gliomas. Median TBRpeak was 7.1 (range: 1.4-19.2) for PET positive tumors. All CNS WHO grade 1 pilocytic astrocytomas/gangliogliomas, grade 3 oligodendrogliomas, and grade 4 glioblastomas/astrocytomas were PET positive, while 25% of grade 2-3 astrocytomas and 56% of grade 2-3 oligodendrogliomas were PET positive. Generally, TBRpeak increased with malignancy grade for diffuse gliomas. A significant difference in PET uptake between CNS WHO grade 2 and 4 gliomas (p < 0.001) and between grade 3 and 4 gliomas (p = 0.002) was observed. Diffuse IDH wildtype gliomas had significantly higher TBRpeak compared to IDH1/2 mutated gliomas (p < 0.001). Adding anti-3-[18F]FACBC PET to MRI improved the accuracy of predicted glioma grades, types, and IDH status, and yielded 13.9 and 16.7 percentage point improvement in the overall diagnoses for both readers, respectively. CONCLUSION: Anti-3-[18F]FACBC PET demonstrated high uptake in the majority of gliomas, especially in IDH wildtype gliomas, and improved the accuracy of preoperatively predicted glioma diagnoses. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04111588, URL: https://clinicaltrials.gov/study/NCT04111588.

Radiological features of brain hemorrhage through automated segmentation from computed tomography in stroke and traumatic brain injury.

Introduction: Radiological assessment is necessary to diagnose spontaneous intracerebral hemorrhage (ICH) and traumatic brain injury intracranial hemorrhage (TBI-bleed). Artificial intelligence (AI) deep learning tools provide a means for decision support. This study evaluates the hemorrhage segmentations produced from three-dimensional deep learning AI model that was developed using non-contrast computed tomography (CT) imaging data external to the current study. Methods: Non-contrast CT imaging data from 1263 patients were accessed across seven data sources (referred to as sites) in Norway and Sweden. Patients were included based on ICH, TBI-bleed, or mild TBI diagnosis. Initial non-contrast CT images were available for all participants. Hemorrhage location frequency maps were generated. The number of estimated haematoma clusters was correlated with the total haematoma volume. Ground truth expert annotations were available for one ICH site; hence, a comparison was made with the estimated haematoma volumes. Segmentation volume estimates were used in a receiver operator characteristics (ROC) analysis for all samples (i.e., bleed detected) and then specifically for one site with few TBI-bleed cases. Results: The hemorrhage frequency maps showed spatial patterns of estimated lesions consistent with ICH or TBI-bleed presentations. There was a positive correlation between the estimated number of clusters and total haematoma volume for each site (correlation range: 0.45-0.74; each p-value < 0.01) and evidence of ICH between-site differences. Relative to hand-drawn annotations for one ICH site, the VIOLA-AI segmentation mask achieved a median Dice Similarity Coefficient of 0.82 (interquartile range: 0.78 and 0.83), resulting in a small overestimate in the haematoma volume by a median of 0.47 mL (interquartile range: 0.04 and 1.75 mL). The bleed detection ROC analysis for the whole sample gave a high area-under-the-curve (AUC) of 0.92 (with sensitivity and specificity of 83.28% and 95.41%); however, when considering only the mild head injury site, the TBI-bleed detection gave an AUC of 0.70. Discussion: An open-source segmentation tool was used to visualize hemorrhage locations across multiple data sources and revealed quantitative hemorrhage site differences. The automated total hemorrhage volume estimate correlated with a per-participant hemorrhage cluster count. ROC results were moderate-to-high. The VIOLA-AI tool had promising results and might be useful for various types of intracranial hemorrhage.

Astrocytoma (CNS WHO grade 4), IDH-mutant with co-occurrence of BRAF p.V600E mutation, and homozygous loss of CDKN2A.

Molecular alterations nowadays play a crucial role in the diagnosis of brain tumors. Some of these alterations are associated with outcome and/or response to treatment, including sequence variants of isocitrate dehydrogenase (IDH) at position p.R132 or p.R172. Such IDH variants have so far been described in histone H3-wildtype primary brain tumors only in adult-type diffuse gliomas and are associated with a better outcome compared to their IDH-wildtype counterpart, the glioblastoma. Moreover, homozygous loss of CDKN2A and/or CDKN2B in IDH-mutant astrocytomas shortens the median overall survival regardless of histological features of malignancy. Such tumors are therefore considered to be aggressive and graded as WHO central nervous system (CNS) grade 4 lesions. The coexistence of an IDH-sequence variation and a BRAF p.V600E alteration has only rarely been described in diffuse astrocytomas. Due to the small number of cases, little is known about such neoplasms in terms of clinical behavior and response to treatment. Herein we describe the first case, to our knowledge, of an astrocytoma (CNS WHO grade 4), IDH-mutant, and BRAF p.V600E-mutant with homozygous deletion of CDKN2A. Pathologists should be aware that such an expression profile does exist even in WHO CNS grade 4 astrocytomas, IDH-mutant, and are encouraged to test for the BRAF p.V600E sequence variant as such an alteration may provide additional treatment options.

Incidence of emergency neurosurgical TBI procedures: a population-based study.

BACKGROUND: The rates of emergency neurosurgery in traumatic brain injury (TBI) patients vary between populations and trauma centers. In planning acute TBI treatment, knowledge about rates and incidence of emergency neurosurgery at the population level is of importance for organization and planning of specialized health care services. This study aimed to present incidence rates and patient characteristics for the most common TBI-related emergency neurosurgical procedures. METHODS: Oslo University Hospital is the only trauma center with neurosurgical services in Southeast Norway, which has a population of 3 million. We extracted prospectively collected registry data from the Oslo TBI Registry - Neurosurgery over a five-year period (2015-2019). Incidence was calculated in person-pears (crude) and age-adjusted for standard population. We conducted multivariate multivariable logistic regression models to assess variables associated with emergency neurosurgical procedures. RESULTS: A total of 2151 patients with pathological head CT scans were included. One or more emergency neurosurgical procedure was performed in 27% of patients. The crude incidence was 3.9/100,000 person-years. The age-adjusted incidences in the standard population for Europe and the world were 4.0/100,000 and 3.3/100,000, respectively. The most frequent emergency neurosurgical procedure was the insertion of an intracranial pressure monitor, followed by evacuation of the mass lesion. Male sex, road traffic accidents, severe injury (low Glasgow coma score) and CT characteristics such as midline shift and compressed/absent basal cisterns were significantly associated with an increased probability of emergency neurosurgery, while older age was associated with a decreased probability. CONCLUSIONS: The incidence of emergency neurosurgery in the general population is low and reflects neurosurgery procedures performed in patients with severe injuries. Hence, emergency neurosurgery for TBIs should be centralized to major trauma centers.

A woman in her forties with unilateral blurred vision and pain upon eye movement. / En kvinne i 40-årene med ensidig tåkesyn og smerter ved øyebevegelse.

BACKGROUND: Toxoplasmosis is a relatively common cause of infectious papillitis and neuroretinitis, which may affect both immunocompetent and immunodeficient patients. CASE PRESENTATION: A previously healthy woman in her mid-forties presented with subacute onset of unilateral blurred vision and retrobulbar pain exacerbated by eye movements. Ophthalmological assessment revealed decimal best-corrected visual acuity of 0.75, an ipsilateral swollen disc and a peripapillary infiltrate. Serology indicated acute infection with Toxoplasma gondii. Cerebral MRI showed a periventricular lesion, and oligoclonal bands were detected in the cerebrospinal fluid. INTERPRETATION: This case illustrates that even when symptoms, MRI and cerebrospinal fluid findings suggest demyelinating disease, differential diagnoses must be considered in order to mitigate the negative therapeutic and prognostic consequences of a misdiagnosis.

Bilateral calcification of the optic nerve sheath: A diagnostic dilemma.

PURPOSE: To present a case of symptomatic optic nerve sheath calcification and highlight clues and pitfalls for the final diagnosis: bilateral optic nerve sheath meningioma. OBSERVATIONS: A 48-year-old man presented with painless vision loss in his left eye and findings consistent with left optic nerve atrophy. Magnetic resonance imaging (MRI) displayed thinning of the left optic nerve without contrast-enhancement or evidence of compressive lesions. A supplementary computed tomography angiography (CTA) exposed scattered dural calcification, which included the optic nerves. This was regarded as an incidental finding. The initial diagnosis was ischemic optic neuropathy. Over the next two years, the vision loss in the left eye progressed. A CT of the orbits revealed extensive calcification surrounding both optic nerves. A second MRI was unchanged in comparison to the first MRI. The diagnosis was changed to idiopathic duro-optic calcification. The vision in the left eye further declined over another two years. Consecutive optical coherence tomography measurements of the peripapillary retinal nerve fiber layer suggested bilateral progressive thinning. A third MRI displayed progression of tubular contrast-enhancement surrounding the optic nerves. On the basis of this finding, the patient was finally diagnosed with a bilateral optic nerve sheath meningioma and received external beam radiotherapy. CONCLUSION AND IMPORTANCE: It is crucial to differentiate an optic nerve sheath meningioma from idiopathic calcification of the optic nerve. In the present case the initial MRI did not detect optic nerve sheath abnormalities. To better demonstrate characteristic calcification, additional CT imaging should be considered when a bilateral optic nerve sheath meningioma is suspected.

Traumatic brain injury-the effects of patient age on treatment intensity and mortality.

BACKGROUND: Ageing is associated with worse treatment outcome after traumatic brain injury (TBI). This association may lead to a self-fulfilling prophecy that affects treatment efficacy. The aim of the current study was to evaluate the role of treatment bias in patient outcomes by studying the intensity of diagnostic procedures, treatment, and overall 30-day mortality in different age groups of patients with TBI. METHODS: Included in this study was consecutively admitted patients with TBI, aged ≥ 15 years, with a cerebral CT showing intracranial signs of trauma, during the time-period between 2015-2018. Data were extracted from our prospective quality control registry for admitted TBI patients. As a measure of management intensity in different age groups, we made a composite score, where placement of intracranial pressure monitor, ventilator treatment, and evacuation of intracranial mass lesion each gave one point. Uni- and multivariate survival analyses were performed using logistic multinomial regression. RESULTS: A total of 1,571 patients with TBI fulfilled the inclusion criteria. The median age was 58 years (range 15-98), 70% were men, and 39% were ≥ 65 years. Head injury severity was mild in 706 patients (45%), moderate in 437 (28%), and severe in 428 (27%). Increasing age was associated with less management intensity, as measured using the composite score, irrespective of head injury severity. Multivariate analyses showed that the following parameters had a significant association with an increased risk of death within 30 days of trauma: increasing age, severe comorbidities, severe TBI, Rotterdam CT-score ≥ 3, and low management intensity. CONCLUSION: The present study indicates that the management intensity of hospitalised patients with TBI decreased with advanced age and that low management intensity was associated with an increased risk of 30-day mortality. This suggests that the high mortality among elderly TBI patients may have an element of treatment bias and could in the future be limited with a more aggressive management regime.

Characteristics of traumatic brain injury patients with abnormal neuroimaging in Southeast Norway.

BACKGROUND: The vast majority of hospital admitted patients with traumatic brain injury (TBI) will have intracranial injury identified by neuroimaging, requiring qualified staff and hospital beds. Moreover, increased pressure in health care services is expected because of an aging population. Thus, a regular evaluation of characteristics of hospital admitted patients with TBI is needed. Oslo TBI Registry - Neurosurgery prospectively register all patients with TBI identified by neuroimaging admitted to a trauma center for southeast part of Norway. The purpose of this study is to describe this patient population with respect to case load, time of admission, age, comorbidity, injury mechanism, injury characteristics, length of stay, and 30-days survival. METHODS: Data for 5 years was extracted from Oslo TBI Registry - Neurosurgery. Case load, time of admission, age, sex, comorbidity, injury mechanism, injury characteristics, length of stay, and 30-days survival was compiled and compared. RESULTS: From January 1st, 2015 to December 31st, 2019, 2153 consecutive patients with TBI identified by neuroimaging were registered. The admission rate of TBI of all severities has been stable year-round since 2015. Mean age was 52 years (standard deviation 25, range 0-99), and 68% were males. Comorbidities were common; 28% with pre-injury ASA score of ≥3 and 25% used antithrombotic medication. The dominating cause of injury in all ages was falls (55%) but increased with age. Upon admission, the head injury was classified as mild TBI in 46%, moderate in 28%, and severe (Glasgow coma score ≤ 8) in 26%. Case load was stable without seasonal variation. Majority of patients (68%) were admitted during evening, night or weekend. 68% was admitted to intensive care unit. Length of hospital stay was 4 days (median, interquartile range 3-9). 30-day survival for mild, moderate and severe TBI was 98, 94 and 69%, respectively. CONCLUSIONS: The typical TBI patients admitted to hospital with abnormal neuroimaging were aged 50-79 years, often with significant comorbidity, and admitted outside ordinary working hours. This suggests the necessity for all-hour presence of competent health care professionals.

Texture analysis on diffusion tensor imaging: discriminating glioblastoma from single brain metastasis.

BACKGROUND: Texture analysis has been done on several radiological modalities to stage, differentiate, and predict prognosis in many oncologic tumors. PURPOSE: To determine the diagnostic accuracy of discriminating glioblastoma (GBM) from single brain metastasis (MET) by assessing the heterogeneity of both the solid tumor and the peritumoral edema with magnetic resonance imaging (MRI) texture analysis (MRTA). MATERIAL AND METHODS: Preoperative MRI examinations done on a 3-T scanner of 43 patients were included: 22 GBM and 21 MET. MRTA was performed on diffusion tensor imaging (DTI) in a representative region of interest (ROI). The MRTA was assessed using a commercially available research software program (TexRAD) which applies a filtration histogram technique for characterizing tumor and peritumoral heterogeneity. The filtration step selectively filters and extracts texture features at different anatomical scales varying from 2 mm (fine) to 6 mm (coarse). Heterogeneity quantification was obtained by the statistical parameter entropy. A threshold value to differentiate GBM from MET with sensitivity and specificity was calculated by receiver operating characteristic (ROC) analysis. RESULTS: Quantifying the heterogeneity of the solid part of the tumor showed no significant difference between GBM and MET. However, the heterogeneity of the GBMs peritumoral edema was significantly higher than the edema surrounding MET, differentiating them with a sensitivity of 80% and specificity of 90%. CONCLUSION: Assessing the peritumoral heterogeneity can increase the radiological diagnostic accuracy when discriminating GBM and MET. This will facilitate the medical staging and optimize the planning for surgical resection of the tumor and postoperative management.

Hyperbaric oxygen therapy of air embolus in the cerebral venous sinuses after intracranial surgery: a case report.

A case with cerebral venous air embolism (CVAE) after neurosurgery and treated with hyperbaric oxygen therapy (HBOT) is presented. This is a rare and potentially fatal complication that neurosurgeons should be aware of. A 52-year-old male was diagnosed with an intracerebral hematoma. An emergency evacuation of the hematoma was performed with a craniotomy and the postoperative CT scan showed a complete evacuation of the hematoma, but it also revealed a CVAE. The patient was immediately referred to HBOT and received three sessions within 48 h. The CT scan after the first HBOT showed no CVAE, venous thrombosis, or new hematoma.

Diagnostic performance of texture analysis on MRI in grading cerebral gliomas.

BACKGROUND AND PURPOSE: Grading of cerebral gliomas is important both in treatment decision and assessment of prognosis. The purpose of this study was to determine the diagnostic accuracy of grading cerebral gliomas by assessing the tumor heterogeneity using MRI texture analysis (MRTA). MATERIAL AND METHODS: 95 patients with gliomas were included, 27 low grade gliomas (LGG) all grade II and 68 high grade gliomas (HGG) (grade III=34 and grade IV=34). Preoperative MRI examinations were performed using a 3T scanner and MRTA was done on preoperative contrast-enhanced three-dimensional isotropic spoiled gradient echo images in a representative ROI. The MRTA was assessed using a commercially available research software program (TexRAD) that applies a filtration-histogram technique for characterizing tumor heterogeneity. Filtration step selectively filters and extracts texture features at different anatomical scales varying from 2mm (fine features) to 6mm (coarse features), the statistical parameter standard deviation (SD) was obtained. Receiver operating characteristics (ROC) was performed to assess sensitivity and specificity for differentiating between the different grades and calculating a threshold value to quantify the heterogeneity. RESULTS: LGG and HGG was best discriminated using SD at fine texture scale, with a sensitivity and specificity of 93% and 81% (AUC 0.910, p<0.0001). The diagnostic ability for MRTA to differentiate between the different sub-groups (grade II-IV) was slightly lower but still significant. CONCLUSIONS: Measuring heterogeneity in gliomas to discriminate HGG from LGG and between different histological sub-types on already obtained images using MRTA can be a useful tool to augment the diagnostic accuracy in grading cerebral gliomas and potentially hasten treatment decision.

Measurements of heterogeneity in gliomas on computed tomography relationship to tumour grade.

To undertake a preliminary study that uses CT texture analysis (CTTA) to quantify heterogeneity in gliomas on contrast-enhanced CT and to assess the relationship between tumour heterogeneity and grade. Retrospective analysis of contrast enhanced CT images was performed in 44 patients with histologically proven cerebral glioma between 2007 and 2010. 11 tumours were low grade (Grade I = 3; Grade II, = 8) and 33 high grade (Grade III = 10, Grade IV = 23). CTTA assessment of tumour heterogeneity was performed using a proprietary software algorithm (TexRAD) that selectively filters and extracts textures at different anatomical scales between filter values 1.0 (fine detail) and 2.5 (coarse features). Heterogeneity was quantified as standard deviation (SD) with or without filtration. Tumour heterogeneity, size and attenuation were correlated with tumour grade. For each parameter, receiver operating characteristics characterised the diagnostic performance for discrimination of high grade from low grade glioma and of grade III tumours from grade IV. Further the CTTA was compared to the radiological diagnosis. Tumour heterogeneity correlated significantly with grade (SD without filtration rs = 0.664, p < 0.001, SD with coarse filtration (rs = 0.714, p < 0.001). Tumour size and attenuation showed only moderate correlations with tumour grade (rs = 0.426, p = 0.004 and rs = 0.447, p = 0.002 respectively). Coarse texture was the best discriminator between high and low grade tumours (AUC 0.832, p < 0.0001) and between grade III and grade IV gliomas (AUC = 0.878 p = 0.0001). Compared to the radiological diagnosis, CTTA further characterised the indetermined cases. By quantifying tumour heterogeneity, CTTA has the potential to provide a marker of tumour grade for patients with cerebral glioma. By differentiating between high and low grade tumours, CTTA could possibly assist clinical management.

Stakeholder perspectives on the use of positron emission tomography in phase III oncology trials in the UK.

AIM: To identify factors that influence the use of PET in phase III oncology trials in the UK by evaluating stakeholder perspectives. METHODS: A wide range of UK PET research stakeholders with a potential interest in the use of PET in phase III trials were identified and invited to participate. These UK PET research stakeholders were consulted using a semistructured questionnaire on their personal experience with and involvement in PET research, the role of PET in phase III oncology clinical trials and on the promotion of UK PET research and unmet clinical needs in oncology. Responses were analysed quantitatively and by qualitative content analysis of free-text responses. RESULTS: A total of 118 responses were received from a wide range of stakeholders representing several professional groups and working environments. Of these respondents, 49 (42%) were using PET in their research. There was the general perception that using PET in clinical research is beneficial in oncology. The two major barriers identified were poor availability of PET and perceived difficulties in funding of excess treatment costs (75% of respondents). Other factors included limited coverage of PET in training, uncertainty about developing imaging protocols or the status of tracers other than 18F-fluorodeoxyglucose, and low awareness of the role of PET in patient selection for therapeutic trials. Patient concerns about radiation were not perceived as a research barrier. CONCLUSION: Interventions that improve the availability and funding pathways for PET research scans and that increase researcher awareness could help promote the use of PET for phase III oncology trials in the UK.