18F-FACBC and 18F-FDG PET/MRI in the evaluation of 3 patients with primary central nervous system lymphoma: a pilot study.

BACKGROUND: This PET/MRI study compared contrast-enhanced MRI, 18F-FACBC-, and 18F-FDG-PET in the detection of primary central nervous system lymphomas (PCNSL) in patients before and after high-dose methotrexate chemotherapy. Three immunocompetent PCNSL patients with diffuse large B-cell lymphoma received dynamic 18F-FACBC- and 18F-FDG-PET/MRI at baseline and response assessment. Lesion detection was defined by clinical evaluation of contrast enhanced T1 MRI (ce-MRI) and visual PET tracer uptake. SUVs and tumor-to-background ratios (TBRs) (for 18F-FACBC and 18F-FDG) and time-activity curves (for 18F-FACBC) were assessed. RESULTS: At baseline, seven ce-MRI detected lesions were also detected with 18F-FACBC with high SUVs and TBRs (SUVmax:mean, 4.73, TBRmax: mean, 9.32, SUVpeak: mean, 3.21, TBRpeak:mean: 6.30). High TBR values of 18F-FACBC detected lesions were attributed to low SUVbackground. Baseline 18F-FDG detected six lesions with high SUVs (SUVmax: mean, 13.88). In response scans, two lesions were detected with ce-MRI, while only one was detected with 18F-FACBC. The lesion not detected with 18F-FACBC was a small atypical MRI detected lesion, which may indicate no residual disease, as this patient was still in complete remission 12 months after initial diagnosis. No lesions were detected with 18F-FDG in the response scans. CONCLUSIONS: 18F-FACBC provided high tumor contrast, outperforming 18F-FDG in lesion detection at both baseline and in response assessment. 18F-FACBC may be a useful supplement to ce-MRI in PCNSL detection and response assessment, but further studies are required to validate these findings. Trial registration ClinicalTrials.gov. Registered 15th of June 2017 (Identifier: NCT03188354, https://clinicaltrials.gov/study/NCT03188354 ).

The STRAT-PARK cohort: A personalized initiative to stratify Parkinson's disease.

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.

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.

Diagnostic Value of 18 F-FACBC PET/MRI in Brain Metastases.

PURPOSE: The study aims to evaluate whether combined 18 F-FACBC PET/MRI could provide additional diagnostic information compared with MRI alone in brain metastases. PATIENTS AND METHODS: Eighteen patients with newly diagnosed or suspected recurrence of brain metastases received dynamic 18 F-FACBC PET/MRI. Lesion detection was evaluated on PET and MRI scans in 2 groups depending on prior stereotactic radiosurgery (SRS group) or not (no-SRS group). SUVs, time-activity curves, and volumetric analyses of the lesions were performed. RESULTS: In the no-SRS group, 29/29 brain lesions were defined as "MRI positive." With PET, 19/29 lesions were detected and had high tumor-to-background ratios (TBRs) (D max MR , ≥7 mm; SUV max , 1.2-8.4; TBR, 3.9-25.9), whereas 10/29 lesions were undetected (D max MR , ≤8 mm; SUV max , 0.3-1.2; TBR, 1.0-2.7). In the SRS group, 4/6 lesions were defined as "MRI positive," whereas 2/6 lesions were defined as "MRI negative" indicative of radiation necrosis. All 6 lesions were detected with PET (D max MR , ≥15 mm; SUV max , 1.4-4.2; TBR, 3.6-12.6). PET volumes correlated and were comparable in size with contrast-enhanced MRI volumes but were only partially congruent (mean DSC, 0.66). All time-activity curves had an early peak, followed by a plateau or a decreasing slope. CONCLUSIONS: 18 F-FACBC PET demonstrated uptake in brain metastases from cancer of different origins (lung, gastrointestinal tract, breast, thyroid, and malignant melanoma). However, 18 F-FACBC PET/MRI did not improve detection of brain metastases compared with MRI but might detect tumor tissue beyond contrast enhancement on MRI. 18 F-FACBC PET should be further evaluated in recurrent brain metastases.

Transient global amnesia: 7 Tesla MRI reveals more hippocampal lesions with diffusion restriction compared to 1.5 and 3 Tesla MRI.

PURPOSE: To assess the ability of 7 T MRI to detect hippocampal DWI lesions in the acute phase of TGA compared to 1.5 T/3 T MRI. METHODS: Patients with a clinical diagnosis consistent with TGA and a 1.5/3 T MRI underwent an additional 7 T MRI when the 7 T system was available for clinical use, thus serving as their own controls. RESULTS: Thirteen TGA patients with a median age of 68.5 years (range 46-77 years) were included and imaged at 1.5/3 T (median 17 h after onset of symptoms, range 3-23 h) and 7 T (median 23 h after onset, range 15-46 h). The 7 T MRIs were performed a median of 15 h after the 1.5/3 T MRIs (range 1-28 h). At 1.5/3 T, six patients (46%) were found to have at least one hippocampal DWI-lesions supporting the TGA diagnosis, which increased to 11 patients (85%) when examined at 7 T (p = 0.03). At 1.5/3 T, nine hippocampal DWI lesions were detected, which increased to 19 at 7 T, giving an increased detection rate of 111% (p = 0.002). Both neuroradiologists found the hippocampal DWI lesions at 7 T to have higher conspicuity and be easier to categorize as true findings compared to 1.5/3 T. CONCLUSION: Seven-Tesla MRI showed both a statistically significant increase in the total number of detected hippocampal DWI lesions and the proportion of patients with at least one hippocampal DWI lesion supporting the TGA diagnosis compared to 1.5/3 T. Clinical use of 7 T will increase the number of patients having their TGA diagnosis supported by MRI, which can be especially useful in patients with negative 1.5/3 T MRI and low clinical certainty.

18F-FACBC PET/MRI in the evaluation of human brain metastases: a case report.

BACKGROUND: Patients with metastatic cancer to the brain have a poor prognosis. In clinical practice, MRI is used to delineate, diagnose and plan treatment of brain metastases. However, MRI alone is limited in detecting micro-metastases, delineating lesions and discriminating progression from pseudo-progression. Combined PET/MRI utilises superior soft tissue images from MRI and metabolic data from PET to evaluate tumour structure and function. The amino acid PET tracer 18F-FACBC has shown promising results in discriminating high- and low-grade gliomas, but there are currently no reports on its use on brain metastases. This is the first study to evaluate the use of 18F-FACBC on brain metastases. CASE PRESENTATION: A middle-aged female patient with brain metastases was evaluated using hybrid PET/MRI with 18F-FACBC before and after stereotactic radiotherapy, and at suspicion of recurrence. Static/dynamic PET and contrast-enhanced T1 MRI data were acquired and analysed. This case report includes the analysis of four 18F-FACBC PET/MRI examinations, investigating their utility in evaluating functional and structural metastasis properties. CONCLUSION: Analysis showed high tumour-to-background ratios in brain metastases compared to other amino acid PET tracers, including high uptake in a very small cerebellar metastasis, suggesting that 18F-FACBC PET can provide early detection of otherwise overlooked metastases. Further studies to determine a threshold for 18F-FACBC brain tumour boundaries and explore its utility in clinical practice should be performed.

Normative data for pituitary size and volume in the general population between 50 and 66 years.

PURPOSE: The main aim of this study was to provide normative data for pituitary height and volume in persons between 50 and 66 years in the general population. The secondary aim was to establish a convenient surrogate marker of pituitary size for use in routine radiological practice. METHODS: From a geographically defined prospective healthy study, 1006 participants between 50 and 66 years had a brain MRI, of which 988 (519 women) were included in this study. We measured the mid-sagittal height, max-sagittal height and total volume of the anterior pituitary lobe based on T1-weighted 3D MRI images. RESULTS: Both the mean mid-sagittal and max-sagittal pituitary height were significantly larger in women compared to men, with 4.9 ± 1.7 mm versus 4.4 ± 1.4 mm (p < .001) for the mean mid-sagittal height and 6.8 ± 1.2 mm versus 6.1 ± 1.1 mm (p < 0.001) for the mean max-sagittal height. The mean anterior pituitary lobe volume was also significantly larger in women than in men (494 ± 138 mm3 vs. 405 ± 118 mm3) (p < 0.001). There were no significant differences in these pituitary sagittal heights nor volume in either sex between the age groups 50-54, 55-59 and 60-66 years. The 95th percentile for mid-sagittal height, max-sagittal height and pituitary volume was 7.7 mm, 8.6 mm and 851 mm3 for women and 6.6 mm, 7.8 mm and 610 mm3 for men. CONCLUSION: This study show that women have a larger pituitary gland than men in the age group between 50 and 66 years and provides normative data for pituitary size estimates which can be used for clinical diagnostic purposes as well as future research.

Survival of glioblastoma in relation to tumor location: a statistical tumor atlas of a population-based cohort.

PURPOSE: Previous studies on the effect of tumor location on overall survival in glioblastoma have found conflicting results. Based on statistical maps, we sought to explore the effect of tumor location on overall survival in a population-based cohort of patients with glioblastoma and IDH wild-type astrocytoma WHO grade II-III with radiological necrosis. METHODS: Patients were divided into three groups based on overall survival: < 6 months, 6-24 months, and > 24 months. Statistical maps exploring differences in tumor location between these three groups were calculated from pre-treatment magnetic resonance imaging scans. Based on the results, multivariable Cox regression analyses were performed to explore the possible independent effect of centrally located tumors compared to known prognostic factors by use of distance from center of the third ventricle to contrast-enhancing tumor border in centimeters as a continuous variable. RESULTS: A total of 215 patients were included in the statistical maps. Central tumor location (corpus callosum, basal ganglia) was associated with overall survival < 6 months. There was also a reduced overall survival in patients with tumors in the left temporal lobe pole. Tumors in the dorsomedial right temporal lobe and the white matter region involving the left anterior paracentral gyrus/dorsal supplementary motor area/medial precentral gyrus were associated with overall survival > 24 months. Increased distance from center of the third ventricle to contrast-enhancing tumor border was a positive prognostic factor for survival in elderly patients, but less so in younger patients. CONCLUSIONS: Central tumor location was associated with worse prognosis. Distance from center of the third ventricle to contrast-enhancing tumor border may be a pragmatic prognostic factor in elderly patients.

MGMT Promoter Methylation Status Is Not Related to Histological or Radiological Features in IDH Wild-type Glioblastomas.

O6-methylguanine DNA methyltransferase (MGMT) promoter methylation is an important favorable predictive marker in patients with glioblastoma (GBM). We hypothesized that MGMT status could be a surrogate marker of pretreatment tumor biology observed as histopathological and radiological features. Apart from some radiological studies aiming to noninvasively predict the MGMT status, few studies have investigated relationships between MGMT status and phenotypical tumor biology. We have therefore aimed to investigate such relationships in 85 isocitrate dehydrogenase (IDH) wild-type GBMs. MGMT status was determined by methylation-specific PCR and was assessed for associations with 22 histopathological features, immunohistochemical proliferative index and microvessel density measurements, conventional magnetic resonance imaging characteristics, preoperative speed of tumor growth, and overall survival. None of the investigated histological or radiological features were significantly associated with MGMT status. Methylated MGMT status was a significant independent predictor of improved overall survival. In conclusion, our results suggest that MGMT status is not related to the pretreatment phenotypical biology in IDH wild-type GBMs. Furthermore, our findings suggest the survival benefit of MGMT methylated GBMs is not due to an inherently less aggressive tumor biology, and that conventional magnetic resonance imaging features cannot be used to noninvasively predict the MGMT status.

Open-Label, Multi-Dose, Pilot Safety Study of Injection of OnabotulinumtoxinA Toward the Otic Ganglion for the Treatment of Intractable Chronic Cluster Headache.

BACKGROUND: The otic ganglion (OG) provides parasympathetic innervation to the cerebral circulation and cranial structures and may be involved in the pathophysiology of trigeminal autonomic headaches. This structure has never been targeted in any headache disorder. OBJECTIVE: To investigate the safety of injecting onabotulinumtoxin A (BTA) toward the OG in 10 patients with intractable chronic cluster headache and to collect efficacy data. METHODS: A total of 10 patients with chronic cluster headache were enrolled in this open-label, multi-dose pilot safety study. All patients were recruited and treated on an out-patient basis at St Olav's University Hospital (Norway). In 5 patients each, the OG was the injection target with 12.5 IU of BTA or 25 IU, respectively. The primary outcome measure was adverse events (AEs) and the main secondary outcome was the number of attacks per week measured at baseline and in the second month following injection. RESULTS: For the primary endpoint, we analyzed data for all 10 patients. There were a total of 17 AEs in 6 of the 10 patients. All AEs were considered mild and disappeared by the end of follow-up. The median number of attacks per week at baseline was 17.0 [7.8 to 25.8] vs 14.0 [7.3 to 20.0] in the second month following injection; difference: 3 (95%CI: -0.3 to 7.9), P = .063. CONCLUSIONS: Injection with BTA toward the OG appears to be safe. We did not find a statistically significant reduction in the number of attacks per week at month 2 after injection compared to the baseline. This study suggests that the OG is not an important target for the treatment of chronic cluster headache. A future study employing more precise targeting of the OG may be indicated.

Is the anatomical distribution of low-grade gliomas linked to regions of gliogenesis?

INTRODUCTION: According to the stem cell theory, two neurogenic niches in the adult human brain may harbor cells that initiate the formation of gliomas: The larger subventricular zone (SVZ) and the subgranular zone (SGZ) in the hippocampus. We wanted to explore whether defining molecular markers in low-grade gliomas (LGG; WHO grade II) are related to distance to the neurogenic niches. METHODS: Patients treated at two Norwegian university hospitals with population-based referral were included. Eligible patients had histopathological verified supratentorial low-grade glioma. IDH mutational status and 1p19q co-deletion status was retrospectively assessed. 159 patients were included, and semi-automatic tumor segmentation was done from pre-treatment T2-weighted (T2W) or Fluid-Attenuated Inversion Recovery (FLAIR) images. 3D maps showing the anatomical distribution of the tumors were then created for each of the three molecular subtypes (IDH mutated/1p19q co-deleted, IDH mutated and IDH wild-type). Both distance from tumor center and tumor border to the neurogenic niches were recorded. RESULTS: In this population-based cohort of previously untreated low-grade gliomas, we found that low-grade gliomas are more often found closer to the SVZ than the SGZ, but IDH wild-type tumors are more often found near SGZ. CONCLUSION: Our study suggests that the stem cell origin of IDH wild-type and IDH mutated low-grade gliomas may be different.

Express Team-Based Learning (eTBL): A Time-Efficient TBL Approach in Neuroradiology.

RATIONALE AND OBJECTIVES: Team-based learning (TBL) is a student-centred, teacher-directed instructional method that promotes active learning. The application phase of TBL stimulates group discussion and critical thinking, which could be useful for learning radiology. We designed and evaluated two modified TBL-sessions on computed tomography and magnetic resonance imaging diagnostics in neuroradiology. Our aim was to examine what effects engaging students in in-class team application tasks had on student learning. MATERIALS AND METHODS: A cross-over study was conducted, including 105 third-year medical students using two modified TBL sessions as the active learning intervention compared with two traditional lectures as a control. Student learning was assessed by results on the neuroradiology part of the end-of-year written examination. Student engagement and perceptions were assessed using the Student Self-Report of Engagement Measure and an additional four Likert-type items. RESULTS: There were no statistically significant differences in student scores on the examination. Students reported high levels of engagement, and reported being more satisfied overall with the TBL sessions than traditional lectures. Students rated the TBL sessions higher than lectures on ability to make difficult material comprehensible, ability to engage students and to give them feedback. CONCLUSION: The modified TBL sessions halved in-class teaching time and by omitting the readiness assurance tests, there was more in-class time to focus on problem-solving of real clinical cases. Moreover, shorter sessions may ease implementation of TBL in the curriculum and allow for more frequent sessions. Students were more satisfied with eTBL than lectures, and reported high levels of engagement.

Volumetric segmentation of glioblastoma progression compared to bidimensional products and clinical radiological reports.

BACKGROUND: Detection of progression is clinically important for the management of glioblastoma. We sought to assess the accuracy of clinical radiological reporting and measured bidimensional products to identify radiological glioblastoma progression. The two were compared to volumetric segmentation. METHODS: In this retrospective study, we included 106 patients with histopathologically verified glioblastomas and two separate MRI scans obtained before surgery. Bidimensional products based on measurements on the axial slice with the largest tumor area were calculated, and growth estimations from the clinical radiological reports were retrieved. The two growth estimations were compared to manual volumetric segmentations. Inter-observer agreement using the bidimensional product was assessed using Kappa-statistics and by calculating the difference between two neuroradiologist in percentage change of the bidimensional product for each tumor. RESULTS: Clinical radiological reports and bidimensional products showed fairly equal accuracy when compared to volumetric segmentation with an accuracy of 67% and 66-68%, respectively. There was a difference in median volume increase of 6.9 mL (2.4 vs 9.3 mL, p < 0.001) between tumors evaluated as stable and progressed based on the clinical radiological reports. This difference was 8.1 mL (2.0 vs 10.1 ml, p < 0.001) when using the bidimensional products. The bidimensional product reached a moderate inter-observer agreement with a Kappa value of 0.689. For 32% of the tumors, the two neuroradiologists calculated a difference of more than 25% using bidimensional products. CONCLUSIONS: Clinical radiological reporting and the bidimensional product exhibit similar accuracy. The bidimensional product has moderate inter-observer agreement and is prone to underestimating tumor progression, as an average glioblastoma had to grow 10 mL in order to be classified as progressed. These findings underline the assumption that one should try to move towards volumetric assessment of glioblastoma growth in the future.

Quantitative and clinical impact of MRI-based attenuation correction methods in [18F]FDG evaluation of dementia.

BACKGROUND: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a promising diagnostic imaging tool for the diagnosis of dementia, as PET can add complementary information to the routine imaging examination with MRI. The purpose of this study was to evaluate the influence of MRI-based attenuation correction (MRAC) on diagnostic assessment of dementia with [18F]FDG PET. Quantitative differences in both [18F]FDG uptake and z-scores were calculated for three clinically available (DixonNoBone, DixonBone, UTE) and two research MRAC methods (UCL, DeepUTE) compared to CT-based AC (CTAC). Furthermore, diagnoses based on visual evaluations were made by three nuclear medicine physicians and one neuroradiologist (PETCT, PETDeepUTE, PETDixonBone, PETUTE, PETCT + MRI, PETDixonBone + MRI). In addition, pons and cerebellum were compared as reference regions for normalization. RESULTS: The mean absolute difference in z-scores were smallest between MRAC and CTAC with cerebellum as reference region: 0.15 ± 0.11 σ (DeepUTE), 0.15 ± 0.12 σ (UCL), 0.23 ± 0.20 σ (DixonBone), 0.32 ± 0.28 σ (DixonNoBone), and 0.54 ± 0.40 σ (UTE). In the visual evaluation, the diagnoses agreed with PETCT in 74% (PETDeepUTE), 67% (PETDixonBone), and 70% (PETUTE) of the patients, while PETCT + MRI agreed with PETDixonBone + MRI in 89% of the patients. CONCLUSION: The MRAC research methods performed close to that of CTAC in the quantitative evaluation of [18F]FDG uptake and z-scores. Among the clinically implemented MRAC methods, DixonBone should be preferred for diagnostic assessment of dementia with [18F]FDG PET/MRI. However, as artifacts occur in DixonBone attenuation maps, they must be visually inspected to assure proper quantification.

18F-FACBC PET/MRI in Diagnostic Assessment and Neurosurgery of Gliomas.

PURPOSE: This pilot study aimed to evaluate the amino acid tracer F-FACBC with simultaneous PET/MRI in diagnostic assessment and neurosurgery of gliomas. MATERIALS AND METHODS: Eleven patients with suspected primary or recurrent low- or high-grade glioma received an F-FACBC PET/MRI examination before surgery. PET and MRI were used for diagnostic assessment, and for guiding tumor resection and histopathological tissue sampling. PET uptake, tumor-to-background ratios (TBRs), time-activity curves, as well as PET and MRI tumor volumes were evaluated. The sensitivities of lesion detection and to detect glioma tissue were calculated for PET, MRI, and combined PET/MRI with histopathology (biopsies for final diagnosis and additional image-localized biopsies) as reference. RESULTS: Overall sensitivity for lesion detection was 54.5% (95% confidence interval [CI], 23.4-83.3) for PET, 45.5% (95% CI, 16.7-76.6) for contrast-enhanced MRI (MRICE), and 100% (95% CI, 71.5-100.0) for combined PET/MRI, with a significant difference between MRICE and combined PET/MRI (P = 0.031). TBRs increased with tumor grade (P = 0.004) and were stable from 10 minutes post injection. PET tumor volumes enclosed most of the MRICE volumes (>98%) and were generally larger (1.5-2.8 times) than the MRICE volumes. Based on image-localized biopsies, combined PET/MRI demonstrated higher concurrence with malignant findings at histopathology (89.5%) than MRICE (26.3%). CONCLUSIONS: Low- versus high-grade glioma differentiation may be possible with F-FACBC using TBR. F-FACBC PET/MRI outperformed MRICE in lesion detection and in detection of glioma tissue. More research is required to evaluate F-FACBC properties, especially in grade II and III tumors, and for different subtypes of gliomas.

Intraoperative 3D ultrasound-guided resection of diffuse low-grade gliomas: radiological and clinical results.

OBJECTIVE: Extent of resection (EOR) and residual tumor volume are linked to prognosis in low-grade glioma (LGG) and there are various methods for facilitating safe maximal resection in such patients. In this prospective study the authors assess radiological and clinical results in consecutive patients with LGG treated with 3D ultrasound (US)-guided resection under general anesthesia. METHODS: Consecutive LGGs undergoing primary surgery guided with 3D US between 2008 and 2015 were included. All LGGs were classified according to the WHO 2016 classification system. Pre- and postoperative volumetric assessments were performed, and volumetric results were linked to overall and malignant-free survival. Pre- and postoperative health-related quality of life (HRQoL) was evaluated. RESULTS: Forty-seven consecutive patients were included. Twenty LGGs (43%) were isocitrate dehydrogenase (IDH)-mutated, 7 (14%) were IDH wild-type, 19 (40%) had both IDH mutation and 1p/19q codeletion, and 1 had IDH mutation and inconclusive 1p/19q status. Median resection grade was 93.4%, with gross-total resection achieved in 14 patients (30%). An additional 24 patients (51%) had small tumor remnants < 10 ml. A more conspicuous tumor border (p = 0.02) and lower University of California San Francisco prognostic score (p = 0.01) were associated with less remnant tumor tissue, and overall survival was significantly better with remnants < 10 ml (p = 0.03). HRQoL was maintained or improved in 86% of patients at 1 month. In both cases with severe permanent deficits, relevant ischemia was present on diffusion-weighted postoperative MRI. CONCLUSIONS: Three-dimensional US-guided LGG resections under general anesthesia are safe and HRQoL is preserved in most patients. Effectiveness in terms of EOR appears to be consistent with published studies using other advanced neurosurgical tools. Avoiding intraoperative vascular injury is a key factor for achieving good functional outcome.

Angiogenesis and radiological tumor growth in patients with glioblastoma.

BACKGROUND: The preoperative growth of human glioblastomas (GBMs) has been shown to vary among patients. In animal studies, angiogenesis has been linked to hypoxia and faster growth of GBM, however, its relation to the growth of human GBMs is sparsely studied. We have therefore aimed to look for associations between radiological speed of growth and microvessel density (MVD) counts of the endothelial markers vWF (Factor VIII related antigen) and CD105 (endoglin). METHODS: Preoperative growth was estimated from segmented tumor volumes of two preoperative T1-weighted postcontrast magnetic resonance imaging scans taken ≥14 days apart in patients with newly diagnosed GBMs. A Gompertzian growth curve was computed from the volume data and separated the patients into two groups of either faster or slower tumor growth than expected. MVD counts of the immunohistochemical markers von Willebrand factor (vWF) (a pan-endothelial marker) and CD105 (a marker of proliferating endothelial cells) were assessed for associations with fast-growing tumors using Mann-Whitney U tests and a multivariable binary logistic regression analysis. RESULTS: We found that only CD105-MVD was significantly associated with faster growth in a univariable analysis (p = 0.049). However, CD105-MVD was no longer significant when corrected for the presence of thromboses and high cellular density in a multivariable model, where the latter features were significant independent predictors of faster growth with respective odds ratios 4.2 (95% confidence interval, 1.2, 14.3), p = 0.021 and 2.6 (95% confidence interval, 1.0, 6.5), p = 0.048. CONCLUSIONS: MVDs of neither endothelial marker were independently associated with faster growth, suggesting angiogenesis-independent processes contribute to faster glioblastoma growth.

When did the glioblastoma start growing, and how much time can be gained from surgical resection? A model based on the pattern of glioblastoma growth in vivo.

OBJECTIVES: Observational data on the natural course of tumor growth in humans is sparse, and mathematical models of tumor growth are often needed to answer questions related to growth. In this study, a theoretical model of glioblastoma growth was used to investigate two questions often asked by patients and clinicians. First, when did the tumor start growing? Second, how much survival time can be gained from various extents of surgical resection (EOR)?. PATIENTS AND METHODS: A gompertzian growth curve was fitted from observational data of pre-treatment growth from 106 glioblastoma patients based on repeated volume segmentations. The curve was used to find the theoretical time since tumor initiation. In addition, as a proxy for the potential survival gain from surgery, the number of days until re-growth would reach the preoperative tumor volume were calculated for different extents of resection. RESULTS: The estimated age of the glioblastomas at diagnosis was median 330 days, but ranging from 156 days to 776 days, depending on the tumor volume at diagnosis. The median survival gains from 50%, 75%, 90%, 95% and 99% EOR were, 1.4, 2.5, 3.6, 4.3, and 5.6 months, respectively. However, survival benefit from surgery also depends on lesion volume. In theory, 100 days may be gained from 95% EOR in a 10 mL lesion or a 50% EOR in a 90 ml lesion. CONCLUSION: In conclusion, we postulate that glioblastoma might originate median 330 days before the diagnosis, assuming the same growth pattern and biology from day one. The theoretical survival benefit of glioblastoma resection is much higher with higher EORs, suggesting that the last milliliters of resection matter the most. Our data also suggest that gain from resection is higher in larger lesions, suggesting that lesion volume may be taken into account in clinical decision-making.