11C-Methionine uptake in meningiomas after stereotactic radiotherapy.

OBJECTIVE: 11C-Methionine positron emission tomography (MET-PET) is used for stereotactic radiotherapy planning in meningioma patients. The role of MET-PET during subsequent follow-up (FU) is unclear. We analyzed the uptake of 11C-Methionine before and after stereotactic radiotherapy (SRT) in patients with a complex meningioma and investigated if there was a difference between patients with progressive disease (PD) and stable disease (SD) during FU. METHODS: This retrospective study investigates 62 MET-PETs in 29 complex meningioma patients. Standardized uptake value (SUV)max and SUVpeak tumor-to-normal ratios (T/N-ratios) were calculated, comparing the tumor region with both the mirroring intracranial area and the right frontal gray matter. The difference in 11C-Methionine uptake pre- and post-SRT was analyzed, as well as the change in uptake between PD or SD. RESULTS: Median (IQR) FU duration was 67 months (50.5-91.0). The uptake of 11C-Methionine in meningiomas remained increased after SRT. Neither a statistically significant difference between MET-PETs before and after SRT was encountered, nor a significant difference in one of the four T/N-ratios between patients with SD versus PD with median (IQR) SUVmax T/NR front 2.65 (2.13-3.68) vs 2.97 (1.55-3.54) [p = 0.66]; SUVmax T/Nmirror 2.92 (2.19-3.71) vs 2.95 (1.74-3.60) [p = 0.61]; SUVpeak T/NR front 2.35 (1.64-3.40) vs 2.25 (1.44-3.74) [p = 0.80]; SUVpeak T/Nmirror 2.38 (1.91-3.36) vs 2.35 (1.56-3.72) [p = 0.95]. CONCLUSIONS: Our data do not support use of MET-PET during FU of complex intracranial meningiomas after SRT. MET-PET could not differentiate between progressive or stable disease.

Re-evaluating patient communication and care in angiographically negative subarachnoid hemorrhage: Balancing realism and optimism.

Angiographically negative subarachnoid hemorrhage (anSAH) has traditionally been considered a benign condition, mainly because of favorable outcomes in the acute stage in comparison to the often negative acute outcomes of aneurysmal subarachnoid hemorrhage. However, a growing body of research in recent years shows that anSAH often leads to cognitive impairments, emotional distress, and difficulties in resuming work or other daily life activities. Therefore, in this position paper, we call for a change in neurological care and a shift in patient communication, emphasizing the importance of addressing patient needs and fostering realistic expectations rather than solely focusing on the benign nature of the condition.

Automated magnetic resonance imaging quantification of cerebral parenchymal and ventricular volume following subarachnoid hemorrhage: associations with cognition.

This study aims to investigate cerebral parenchymal and ventricular volume changes after subarachnoid hemorrhage (SAH) and their potential association with cognitive impairment. 17 patients with aneurysmal SAH (aSAH) and 21 patients with angiographically negative SAH (anSAH) without visually apparent parenchymal loss on conventional magnetic resonance imaging (MRI) were included, along with 76 healthy controls. Volumetric analyses were performed using an automated clinical segmentation and quantification tool. Measurements were compared to on-board normative reference database (n = 1923) adjusted for age, sex, and intracranial volume. Cognition was assessed with tests for psychomotor speed, attentional control, (working) memory, executive functioning, and social cognition. All measurements took place 5 months after SAH. Lower cerebral parenchymal volumes were most pronounced in the frontal lobe (aSAH: n = 6 [35%], anSAH n = 7 [33%]), while higher volumes were most substantial in the lateral ventricle (aSAH: n = 5 [29%], anSAH n = 9 [43%]). No significant differences in regional brain volumes were observed between both SAH groups. Patients with lower frontal lobe volume exhibited significantly lower scores in psychomotor speed (U = 81, p = 0.02) and attentional control (t = 2.86, p = 0.004). Additionally, higher lateral ventricle volume was associated with poorer memory (t = 3.06, p = 0.002). Regional brain volume changes in patients with SAH without visible parenchymal abnormalities on MRI can still be quantified using a fully automatic clinical-grade tool, exposing changes which may contribute to cognitive impairment. Therefore, it is important to provide neuropsychological assessment for both SAH groups, also including those with clinically mild symptoms.

Head-to-head comparison of [11C]methionine PET, [11C]choline PET, and 4-dimensional CT as second-line scans for detection of parathyroid adenomas in primary hyperparathyroidism.

PURPOSE: Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most effective after negative first-line imaging. In this study, we compare the diagnostic effectiveness of [11C]methionine PET/CT, [11C]choline PET/CT, and four dimensional (4D)-CT head-to-head in patients with pHPT, to explore which of these imaging techniques to use as a second-line scan. METHODS: We conducted a powered, prospective, blinded cohort study in patients with biochemically proven pHPT and prior negative or discordant first-line imaging consisting of ultrasonography and 99mTc-sestamibi. All patients underwent [11C]methionine PET/CT, [11C]choline PET/CT, and 4D-CT. At first, all scans were interpreted by a nuclear medicine physician, and a radiologist who were blinded from patient data and all imaging results. Next, a non-blinded scan reading was performed. The scan results were correlated with surgical and histopathological findings. Serum calcium values at least 6 months after surgery were used as gold standard for curation of HPT. RESULTS: A total of 32 patients were included in the study. With blinded evaluation, [11C]choline PET/CT was positive in 28 patients (88%), [11C]methionine PET/CT in 23 (72%), and 4D-CT in 15 patients (47%), respectively. In total, 30 patients have undergone surgery and 32 parathyroid lesions were histologically confirmed as parathyroid adenomas. Based on the blinded evaluation, lesion-based sensitivity of [11C]choline PET/CT, [11C]methionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of [11C]choline PET/CT differed significantly from that of [11C]methionine PET/CT and 4D-CT (p = 0.031 and p < 0.0005, respectively). CONCLUSION: In the setting of pHPT with negative first-line imaging, [11C]choline PET/CT is superior to [11C]methionine PET/CT and 4D-CT in localizing parathyroid adenomas, allowing correct localization in 85% of adenomas. Further studies are needed to determine cost-benefit and efficacy of these scans, including the timing of these scans as first- or second-line imaging techniques.

Emotion recognition in relation to tumor characteristics in patients with low-grade glioma.

BACKGROUND: Patients with low-grade gliomas (LGG) treated with surgery, generally function well and have a favorable prognosis. However, LGG can affect neurocognitive functioning. To date, little is known about social cognition (SC) in these patients, although impaired SC is related to social-behavioral problems and poor societal participation. Frontal brain areas are important for SC and LGG frequently have a frontal location. Therefore, the aim of the present study was to investigate whether emotion recognition, a key component of SC, was impaired, and related to general cognition, tumor location, laterality, tumor volume, and histopathological characteristics in patients with LGG, postsurgery, and before start of adjuvant therapy. METHODS: A total of 121 patients with LGG were matched with 169 healthy controls (HC). Tumor location [including (frontal) subregions; insula, anterior cingulate cortex, lateral prefrontal cortex (LPFC), orbitofrontal-ventromedial PFC] and tumor volume were determined on MRI scans. Emotion recognition was measured with the Ekman 60 faces test of the Facial Expressions of Emotion-Stimuli and Tests (FEEST). RESULTS: Patients with LGG performed significantly lower on the FEEST than HC, with 33.1% showing impairment compared to norm data. Emotion recognition was not significantly correlated to frontal tumor location, laterality, and histopathological characteristics, and significantly but weakly with general cognition and tumor volume. CONCLUSIONS: Emotion recognition is impaired in patients with LGG but not (strongly) related to specific tumor characteristics or general cognition. Hence, measuring SC with individual neuropsychological assessment of these patients is crucial, irrespective of tumor characteristics, to inform clinicians about possible impairments, and consequently offer appropriate care.

Influence of MRI Follow-Up on Treatment Decisions during Standard Concomitant and Adjuvant Chemotherapy in Patients with Glioblastoma: Is Less More?

MRI is the gold standard for treatment response assessments for glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, a reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy at 2-3 month intervals actually benefits patients and how it influences clinical decision making about the continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans post-chemoradiotherapy (post-CCRT), after three cycles of adjuvant chemotherapy [TMZ3/6], and after the completion of treatment [TMZ6/6]), and of unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in an early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p < 0.001). Perfusion MRI caused less diagnostic uncertainty (p = 0.021) but did not influence treatment consequences (p = 0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach.

The Correlation of In Vivo MR Spectroscopy and Ex Vivo 2-Hydroxyglutarate Concentration for the Prediction of Isocitrate Dehydrogenase Mutation Status in Diffuse Glioma.

Isocitrate dehydrogenase (IDH) mutation status is an important biomarker in the glioma-defining subtype and corresponding prognosis. This study proposes a straightforward method for 2-hydroxyglutarate (2-HG) quantification by MR spectroscopy for IDH mutation status detection and directly compares in vivo 2-HG MR spectroscopy with ex vivo 2-HG concentration measured in resected tumor tissue. Eleven patients with suspected lower-grade glioma (ten IDH1; one IDHwt) were prospectively included. Preoperatively, 3T point-resolved spectroscopy (PRESS) was acquired; 2-HG was measured as the percentage elevation of Glx3 (the sum of 2-HG and Glx) compared to Glx4. IDH mutation status was assessed by immunochemistry or direct sequencing. The ex vivo 2-HG concentration was determined in surgically obtained tissue specimens using gas chromatography-mass spectrometry. Pearson correlation was used for assessing the correlation between in vivo MR spectroscopy and ex vivo 2-HG concentration. MR spectroscopy was positive for 2-HG in eight patients, all of whom had IDH1 tumors. A strong correlation (r = 0.80, p = 0.003) between 2-HG MR spectroscopy and the ex vivo 2-HG concentration was found. This study shows in vivo 2-HG MR spectroscopy can non-invasively determine IDH status in glioma and demonstrates a strong correlation with ex vivo 2-HG concentration in patients with lower-grade glioma.

Arterial spin labelling MRI for brain tumour surveillance: do we really need cerebral blood flow maps?

OBJECTIVES: Arterial spin labelling (ASL) perfusion MRI is one of the available advanced MRI techniques for brain tumour surveillance. The first aim of this study was to investigate the correlation between quantitative cerebral blood flow (CBF) and non-quantitative perfusion weighted imaging (ASL-PWI) measurements. The second aim was to investigate the diagnostic accuracy of ASL-CBF and ASL-PWI measurements as well as visual assessment for identifying tumour progression. METHODS: A consecutive cohort of patients who underwent 3-T MRI surveillance containing ASL for treated brain tumours was used. ROIs were drawn in representative parts of tumours in the ASL-CBF maps and copied to the ASL-PWI. ASL-CBF ratios and ASL-PWI ratios of the tumour ROI versus normal appearing white matter (NAWM) were correlated (Pearson correlation) and AUCs were calculated to assess diagnostic accuracy. Additionally, lesions were visually classified as hypointense, isointense, or hyperintense. We calculated accuracy at two thresholds: low threshold (between hypointense-isointense) and high threshold (between isointense-hyperintense). RESULTS: A total of 173 lesions, both enhancing and non-enhancing, measured in 115 patients (93 glioma, 16 metastasis, and 6 lymphoma) showed a very high correlation of 0.96 (95% CI: 0.88-0.99) between ASL-CBF ratios and ASL-PWI ratios. AUC was 0.76 (95%CI: 0.65-0.88) for ASL-CBF ratios and 0.72 (95%CI: 0.58-0.85) for ASL-PWI ratios. Diagnostic accuracy of visual assessment for enhancing lesions was 0.72. CONCLUSION: ASL-PWI ratios and ASL-CBF ratios showed a high correlation and comparable AUCs; therefore, quantification of ASL-CBF could be omitted in these patients. Visual classification had comparable diagnostic accuracy to the ASL-PWI or ASL-CBF ratios. CLINICAL RELEVANCE STATEMENT: This study shows that CBF quantification of ASL perfusion MRI could be omitted for brain tumour surveillance and that visual assessment provides the same diagnostic accuracy. This greatly reduces the complexity of the use of ASL in routine clinical practice. KEY POINTS: • Arterial spin labelling MRI for clinical brain tumour surveillance is undervalued and underinvestigated. • Non-quantitative and quantitative arterial spin labelling assessments show high correlation and comparable diagnostic accuracy. • Quantification of arterial spin labelling MRI could be omitted to improve daily clinical workflow.

Radiologically Defined Sarcopenia as a Biomarker for Frailty and Malnutrition in Head and Neck Skin Cancer Patients.

The aim of this study was to evaluate whether radiologically defined sarcopenia, or a low skeletal muscle index (SMI), could be used as a practical biomarker for frailty and postoperative complications (POC) in patients with head and neck skin cancer (HNSC). This was a retrospective study on prospectively collected data. The L3 SMI (cm2/m2) was calculated with use of baseline CT or MRI neck scans and low SMIs were defined using sex-specific cut-off values. A geriatric assessment with a broad range of validated tools was performed at baseline. POC was graded with the Clavien-Dindo Classification (with a grade of > II as the cut-off). Univariate and multivariable regression analyses were performed with low SMIs and POC as the endpoints. The patients' (n = 57) mean age was 77.0 ± 9 years, 68.4% were male, and 50.9% had stage III-IV cancer. Frailty was determined according to Geriatric 8 (G8) score (OR 7.68, 95% CI 1.19-49.66, p = 0.032) and the risk of malnutrition was determined according to the Malnutrition Universal Screening Tool (OR 9.55, 95% CI 1.19-76.94, p = 0.034), and these were independently related to low SMIs. Frailty based on G8 score (OR 5.42, 95% CI 1.25-23.49, p = 0.024) was the only variable related to POC. However, POC was more prevalent in patients with low SMIs (∆ 19%, OR 1.8, 95% CI 0.5-6.0, p = 0.356).To conclude, a low SMI is a practical biomarker for frailty and malnutrition in HNSC. Future research should be focused on interventions based on low SMI scores and assess the effect of the intervention on SMI, frailty, malnutrition, and POC.

Voxel based morphometry-detected white matter volume loss after multi-modality treatment in high grade glioma patients.

BACKGROUND: Radiotherapy (RT) and chemotherapy are components of standard multi-modality treatment of high grade gliomas (HGG) aimed at achieving local tumor control. Treatment is neurotoxic and RT plays an important role in this, inducing damage even distant to the RT target volume. PURPOSE: This retrospective longitudinal study evaluated the effect of treatment on white matter and gray matter volume in the tumor-free hemisphere of HGG patients using voxel based morphometry (VBM). METHOD: 3D T1-weighted MR images of 12 HGG patients at multiple timepoints during standard treatment were analyzed using VBM. Segmentation of white matter and gray matter of the tumor-free hemisphere was performed. Multiple general linear models were used to asses white matter and gray matter volumetric differences between time points. A mean RT dose map was created and compared to the VBM results. RESULTS: Diffuse loss of white matter volume, mainly throughout the frontal and parietal lobe, was found, grossly overlapping regions that received the highest RT dose. Significant loss of white matter was first noticed after three cycles of chemotherapy and persisted after the completion of standard treatment. No significant loss of white matter volume was observed between pre-RT and the first post-RT follow-up timepoint, indicating a delayed effect. CONCLUSION: This study demonstrated diffuse and early-delayed decreases in white matter volume of the tumor-free hemisphere in HGG patients after standard treatment. White matter volume changes occurred mainly throughout the frontal and parietal lobe and grossly overlapped with areas that received the highest RT dose.

Endovascular treatment versus no endovascular treatment after 6-24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands: a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial.

BACKGROUND: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA). METHODS: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220. FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]). INTERPRETATION: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow. FUNDING: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

Validity of Early Outcomes as Indicators for Comparing Hospitals on Quality of Stroke Care.

Background Insight into outcome variation between hospitals could help to improve quality of care. We aimed to assess the validity of early outcomes as quality indicators for acute ischemic stroke care for patients treated with endovascular therapy (EVT). Methods and Results We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a large multicenter prospective cohort study including 3279 patients with acute ischemic stroke undergoing EVT. Random effect linear and proportional odds regression were used to analyze the effect of case mix on between-hospital differences in 2 early outcomes: the National Institutes of Health Stroke Scale (NIHSS) score at 24 to 48 hours and the expanded thrombolysis in cerebral infarction score. Between-hospital variation in outcomes was assessed using the variance of random hospital effects (tau2). In addition, we estimated the correlation between hospitals' EVT-patient volume and (case-mix-adjusted) outcomes. Both early outcomes and case-mix characteristics varied significantly across hospitals. Between-hospital variation in the expanded thrombolysis in cerebral infarction score was not influenced by case-mix adjustment (tau 2=0.17 in both models). In contrast, for the NIHSS score at 24 to 48 hours, case-mix adjustment led to a decrease in variation between hospitals (tau 2 decreases from 0.19 to 0.17). Hospitals' EVT-patient volume was strongly correlated with higher expanded thrombolysis in cerebral infarction scores (r=0.48) and weakly with lower NIHSS score at 24 to 48 hours (r=0.15). Conclusions Between-hospital variation in NIHSS score at 24 to 48 hours is significantly influenced by case-mix but not by patient volume. In contrast, between-hospital variation in expanded thrombolysis in cerebral infarction score is strongly influenced by EVT-patient volume but not by case-mix. Both outcomes may be suitable for comparing hospitals on quality of care, provided that adequate adjustment for case-mix is applied for NIHSS score.

Timing and causes of death after endovascular thrombectomy in patients with acute ischemic stroke.

Introduction: Endovascular thrombectomy (EVT) increases the chance of good functional outcome after ischemic stroke caused by a large vessel occlusion, but the risk of death in the first 90 days is still considerable. We assessed the causes, timing and risk factors of death after EVT to aid future studies aiming to reduce mortality. Patients and methods: We used data from the MR CLEAN Registry, a prospective, multicenter, observational cohort study of patients treated with EVT in the Netherlands between March 2014, and November 2017. We assessed causes and timing of death and risk factors for death in the first 90 days after treatment. Causes and timing of death were determined by reviewing serious adverse event forms, discharge letters, or other written clinical information. Risk factors for death were determined with multivariable logistic regression. Results: Of 3180 patients treated with EVT, 863 (27.1%) died in the first 90 days. The most common causes of death were pneumonia (215 patients, 26.2%), intracranial hemorrhage (142 patients, 17.3%), withdrawal of life-sustaining treatment because of the initial stroke (110 patients, 13.4%) and space-occupying edema (101 patients, 12.3%). In total, 448 patients (52% of all deaths) died in the first week, with intracranial hemorrhage as most frequent cause. The strongest risk factors for death were hyperglycemia and functional dependency before the stroke and severe neurological deficit at 24-48 h after treatment. Discussion and conclusion: When EVT fails to decrease the initial neurological deficit, strategies to prevent complications like pneumonia and intracranial hemorrhage after EVT could improve survival, as these are often the cause of death.

Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice.

BACKGROUND: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment. METHODS: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes. RESULTS: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). CONCLUSIONS: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.

The validation of low-dose CT scans from the [18F]-FDG PET-CT scan to assess skeletal muscle mass in comparison with diagnostic neck CT scans.

PURPOSE: Radiologically defined sarcopenia, or a low skeletal muscle index (SMI), is an emerging biomarker for adverse clinical outcomes in head and neck cancer (HNC) patients. Recently, SMI measurements have been validated at the level of the third cervical vertebra (C3) on diagnostic neck CT scans but are not yet validated on low-dose (LD) neck CT scans from the [18F]-FDG PET-CT. This hampers SMI analysis in HNC patients without a diagnostic neck CT but with a [18F]-FDG PET-CT scan. Therefore, the aim was to study whether (low) SMI based on LD CT scan from [18F]-FDG PET-CT is comparable to those derived from diagnostic neck CT scans. METHODS: HNC patients with both diagnostic CT and [18F]-FDG PET-CT of the neck were prospectively included into the OncoLifeS data-biobank. Skeletal muscle was retrospectively delineated at the level of the third cervical vertebra (C3), and (low) SMI (cm2/m2) was calculated for diagnostic and LD neck CTs. (Low) SMI from the diagnostic neck CT was considered the reference standard. Intra-class correlation coefficient (ICC), Bland-Altman plots, and Cohen's Kappa analysis were performed. RESULTS: The cohort (n = 233) mean age was 66.2 ± 12.8 years, and 74.2% of patients were male. Inter-rater reliability was excellent (ICC > 0.990, 95% confidence interval 0.975-0.996, p < 0.001). The agreement of SMI between both modalities was high according to the Bland-Altman plot (mean ΔSMI = - 0.19 cm2/m2), and there was no substantial bias. Cohen's Kappa analysis showed an almost perfect agreement of low SMI between the two modalities (κ = 0.911, p < 0.001). The position of arms didn't affect the high agreement of (low) SMI. CONCLUSION: Skeletal muscle mass, as measured with (low) SMI, remains constant irrespective of CT acquisition parameters (diagnostic neck CT scans versus LD neck scans of the [18F]-FDG PET-CT scan), positioning of arms, and observers. These findings contribute to the construction of a clinically useful radiological biomarker for SMI and therefore identify patients at risk for adverse clinical outcomes.

Susceptibility-weighted imaging in intracranial hemorrhage: not all bleeds are black.

To correctly recognize intracranial hemorrhage (ICH) and differentiate it from other lesions, knowledge of the imaging characteristics of an ICH on susceptibility weighted imaging (SWI) is essential. It is a common misconception that blood is always black on SWI, and it is important to realize that hemorrhage has a variable appearance in different stages on SWI. Furthermore, the presence of a low signal on SWI does not equal the presence of blood products. In this review, the appearance of ICH on SWI during all its stages and common other causes of a low signal on SWI are further discussed and illustrated.

Investigation of image-derived input functions for non-invasive quantification of myelin density using [11C]MeDAS PET.

Multiple sclerosis (MS) is an inflammatory demyelinating disease. Current treatments are focussed on immune suppression to modulate pathogenic activity that causes myelin damage. New treatment strategies are needed to prevent demyelination and promote remyelination. Development of such myelin repair therapies require a sensitive and specific biomarker for efficacy evaluation. Recently, it has been shown that quantification of myelin density is possible using [11C]MeDAS PET. This method, however, requires arterial blood sampling to generate an arterial input function (AIF). As the invasive nature of arterial sampling will reduce clinical applicability, the purpose of this study was to assess whether an image-derived input function (IDIF) can be used as an alternative way to facilitate its routine clinical use. Six healthy controls and 11 MS patients underwent MRI and [11C]MeDAS PET with arterial blood sampling. The application of both population-based whole blood-to-plasma conversion and metabolite corrections were assessed for the AIF. Next, summed images of the early time frames (0-70 s) and the frame with the highest blood-brain contrast were used to generate IDIFs. IDIFs were created using either the hottest 2, 4, 6 or 12 voxels, or an isocontour of the hottest 10% voxels of the carotid artery. This was followed by blood-to-plasma conversion and metabolite correction of the IDIF. The application of a population-based metabolite correction of the AIF resulted in high correlations of tracer binding (Ki) within subjects, but variable bias across subjects. All IDIFs had a sharper and higher peak in the blood curves than the AIF, most likely due to dispersion during blood sampling. All IDIF methods resulted in similar high correlations within subjects (r = 0.95-0.98), but highly variable bias across subjects (mean slope=0.90-1.09). Therefore, both the use of population based blood-plasma and metabolite corrections and the generation of the image-derived whole-blood curve resulted in substantial bias in [11C]MeDAS PET quantification, due to high inter-subject variability. Consequently, when unbiased quantification of [11C]MeDAS PET data is required, individual AIF needs to be used.

Diagnostic accuracy of MRI techniques for treatment response evaluation in patients with brain metastasis: A systematic review and meta-analysis.

BACKGROUND: Treatment response assessment in patients with brain metastasis uses contrast enhanced T1-weighted MRI. Advanced MRI techniques have been studied, but the diagnostic accuracy is not well known. Therefore, we performed a metaanalysis to assess the diagnostic accuracy of the currently available MRI techniques for treatment response. METHODS: A systematic literature search was done. Study selection and data extraction were done by two authors independently. Meta-analysis was performed using a bivariate random effects model. An independent cohort was used for DSC perfusion external validation of diagnostic accuracy. RESULTS: Anatomical MRI (16 studies, 726 lesions) showed a pooled sensitivity of 79% and a specificity of 76%. DCE perfusion (4 studies, 114 lesions) showed a pooled sensitivity of 74% and a specificity of 92%. DSC perfusion (12 studies, 418 lesions) showed a pooled sensitivity was 83% with a specificity of 78%. Diffusion weighted imaging (7 studies, 288 lesions) showed a pooled sensitivity of 67% and a specificity of 79%. MRS (4 studies, 54 lesions) showed a pooled sensitivity of 80% and a specificity of 78%. Combined techniques (6 studies, 375 lesions) showed a pooled sensitivity of 84% and a specificity of 88%. External validation of DSC showed a lower sensitivity and a higher specificity for the reported cut-off values included in this metaanalysis. CONCLUSION: A combination of techniques shows the highest diagnostic accuracy differentiating tumor progression from treatment induced abnormalities. External validation of imaging results is important to better define the reliability of imaging results with the different techniques.

Investigating Recovery After Subarachnoid Hemorrhage With the Imaging, Cognition and Outcome of Neuropsychological Functioning After Subarachnoid Hemorrhage (ICONS) Study: Protocol for a Longitudinal, Prospective Cohort Study.

BACKGROUND: A subarachnoid hemorrhage is a hemorrhage in the subarachnoid space that is often caused by the rupture of an aneurysm. Patients who survive a subarachnoid hemorrhage have a high risk of complications and a negative long-term outcome. OBJECTIVE: The aim of the Imaging, Cognition and Outcome of Neuropsychological functioning after Subarachnoid hemorrhage (ICONS) study is to investigate whether and to what extent deficits exist in multiple domains after subarachnoid hemorrhage, including cognition, emotion and behavior, and to investigate whether brain damage can be detected in patients with subarachnoid hemorrhage. We aim to determine which early measures of cognition, emotion and behavior, and brain damage in the subacute stage play a role in long-term recovery after subarachnoid hemorrhage. Recovery is defined as functioning at a societal participation level, with a focus on resuming and maintaining work, leisure activities, and social relationships over the long term. METHODS: The ICONS study is an observational, prospective, single-center cohort study. The study includes patients with subarachnoid hemorrhage admitted to the Neurosurgery Unit of the University Medical Centre Groningen in the Netherlands. The inclusion criteria include diagnosis of an aneurysmal subarachnoid hemorrhage or an angiographically negative subarachnoid hemorrhage, sufficient ability in the Dutch language, and age older than 18 years. Patients will undergo neuropsychological assessment and magnetic resonance imaging 6 months after the subarachnoid hemorrhage. Furthermore, patients will be asked to fill in questionnaires on multiple psychosocial measures and undergo a structured interview at 6 months, 1 year, and 2 years after the subarachnoid hemorrhage. The primary outcome measure of the ICONS study is societal participation 1 year after the subarachnoid hemorrhage, measured with the Dutch version of the Impact on Participation and Autonomy questionnaire. RESULTS: The study was launched in December 2019 and recruitment is expected to continue until June 2023. At the time of the acceptance of this paper, 76 patients and 69 healthy controls have been included. The first results are expected in early 2023. CONCLUSIONS: The ICONS study is the first to collect and combine data after subarachnoid hemorrhage in a variety of domains, including cognition, emotion and behavior, and brain damage. The results will contribute to a more comprehensive understanding of the consequences of both aneurysmal subarachnoid hemorrhage and angiographically negative subarachnoid hemorrhage, which may ultimately optimize timely treatment for this patient group by setting realistic and attainable goals to improve daily functioning. TRIAL REGISTRATION: Netherlands Trial Register NL7803; https://trialsearch.who.int/Trial2.aspx?TrialID=NL7803. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38190.