Feasibility of an MR-based digital specimen for tongue cancer resection specimens: a novel approach for margin evaluation.

Objective: This study explores the feasibility of ex-vivo high-field magnetic resonance (MR) imaging to create digital a three-dimensional (3D) representations of tongue cancer specimens, referred to as the "MR-based digital specimen" (MR-DS). The aim was to create a method to assist surgeons in identifying and localizing inadequate resection margins during surgery, a critical factor in achieving locoregional control. Methods: Fresh resection specimens of nine tongue cancer patients were imaged in a 7 Tesla small-bore MR, using a high-resolution multislice and 3D T2-weighted Turbo Spin Echo. Two independent radiologists (R1 and R2) outlined the tumor and mucosa on the MR-images whereafter the outlines were configured to an MR-DS. A color map was projected on the MR-DS, mapping the inadequate margins according to R1 and R2. We compared the hematoxylin-eosin-based digital specimen (HE-DS), which is a histopathological 3D representation derived from HE stained sections, with its corresponding MR-images. In line with conventional histopathological assessment, all digital specimens were divided into five anatomical regions (anterior, posterior, craniomedial, caudolateral and deep central). Over- and underestimation 95th-percentile Hausdorff-distances were calculated between the radiologist- and histopathologist-determined tumor outlines. The MR-DS' diagnostic accuracy for inadequate margin detection (i.e. sensitivity and specificity) was determined in two ways: with conventional histopathology and HE-DS as reference. Results: Using conventional histopathology as a reference, R1 achieved 77% sensitivity and 50% specificity, while R2 achieved 65% sensitivity and 57% specificity. When referencing to the HE-DS, R1 achieved 94% sensitivity and 61% specificity, while R2 achieved 88% sensitivity and 71% specificity. Range of over- and underestimation 95HD was 0.9 mm - 11.8 mm and 0.0 mm - 5.3 mm, respectively. Conclusion: This proof of concept for volumetric assessment of resection margins using MR-DSs, demonstrates promising potential for further development. Overall, sensitivity is higher than specificity for inadequate margin detection, because of the radiologist's tendency to overestimate tumor size.

The Additional Value of Somatostatin Receptor Positron Emission Computed Tomography ([68Ga]Ga-DOTATOC PET/CT) Compared with Magnetic Resonance Imaging of the Head and Neck Region in Paraganglioma Patients: A Pilot Study.

The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [68Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations. METHODS: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [68Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs. RESULTS: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [68Ga]Ga-DOTATOC PET/CT. CONCLUSIONS: The authors recommend performing baseline imaging with [68Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [68Ga]Ga-DOTATOC PET/CT.

Improving advanced intraoperative MRI methods during pediatric neurosurgery.

Advanced intraoperative MR images (ioMRI) acquired during the resection of pediatric brain tumors could offer additional physiological information to preserve healthy tissue. With this work, we aimed to develop a protocol for ioMRI with increased sensitivity for arterial spin labeling (ASL) and diffusion MRI (dMRI), optimized for patient positioning regularly used in the pediatric neurosurgery setting. For ethical reasons, ASL images were acquired in healthy adult subjects that were imaged in the prone and supine position. After this, the ASL cerebral blood flow (CBF) was quantified and compared between both positions. To evaluate the impact of the RF coils setups on image quality, we compared different setups (two vs. four RF coils) by looking at T1-weighted (T1w) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), as well as undertaking a qualitative evaluation of T1w, T2w, ASL, and dMR images. Mean ASL CBF did not differ between the surgical prone and supine positions in any of the investigated regions of interest or the whole brain. T1w SNR (gray matter: p = 0.016, 34% increase; white matter: p = 0.016, 32% increase) and CNR were higher (p = 0.016) in the four versus two RF coils setups (18.0 ± 1.8 vs. 13.9 ± 1.8). Qualitative evaluation of T1w, T2w, ASL, and dMR images resulted in acceptable to good image quality and did not differ statistically significantly between setups. Only the nonweighted diffusion image maps and corticospinal tract reconstructions yielded higher image quality and reduced susceptibility artifacts with four RF coils. Advanced ioMRI metrics were more precise with four RF coils as the standard deviation decreased. Taken together, we have investigated the practical use of advanced ioMRI during pediatric neurosurgery. We conclude that ASL CBF quantification in the surgical prone position is valid and that ASL and dMRI acquisition with two RF coils can be performed adequately for clinical use. With four versus two RF coils, the SNR of the images increases, and the sensitivity to artifacts reduces.

Prophylactic pectoralis major flap to compensate for increased risk of pharyngocutaneous fistula in laryngectomy patients with low skeletal muscle mass (PECTORALIS): study protocol for a randomized controlled trial.

BACKGROUND: Total laryngectomy (TL) is a surgical procedure commonly performed on patients with advanced laryngeal or hypopharyngeal carcinoma. One of the most common postoperative complications following TL is the development of a pharyngocutaneous fistula (PCF), characterized by a communication between the neopharynx and the skin. PCF can lead to extended hospital stays, delayed oral feeding, and compromised quality of life. The use of a myofascial pectoralis major flap (PMMF) as an onlay technique during pharyngeal closure has shown potential in reducing PCF rates in high risk patients for development of PCF such as patients undergoing TL after chemoradiation and low skeletal muscle mass (SMM). Its impact on various functional outcomes, such as shoulder and neck function, swallowing function, and voice quality, remains less explored. This study aims to investigate the effectiveness of PMMF in reducing PCF rates in patients with low SMM and its potential consequences on patient well-being. METHODS: This multicenter study adopts a randomized clinical trial (RCT) design and is funded by the Dutch Cancer Society. Eligible patients for TL, aged ≥ 18 years, mentally competent, and proficient in Dutch, will be enrolled. One hundred and twenty eight patients with low SMM will be centrally randomized to receive TL with or without PMMF, while those without low SMM will undergo standard TL. Primary outcome measurement involves assessing PCF rates within 30 days post-TL. Secondary objectives include evaluating quality of life, shoulder and neck function, swallowing function, and voice quality using standardized questionnaires and functional tests. Data will be collected through electronic patient records. DISCUSSION: This study's significance lies in its exploration of the potential benefits of using PMMF as an onlay technique during pharyngeal closure to reduce PCF rates in TL patients with low SMM. By assessing various functional outcomes, the study aims to provide a comprehensive understanding of the impact of PMMF deployment. The anticipated results will contribute valuable insights into optimizing surgical techniques to enhance patient outcomes and inform future treatment strategies for TL patients. TRIAL REGISTRATION: NL8605, registered on 11-05-2020; International Clinical Trials Registry Platform (ICTRP).

Low dose cisplatin weekly versus high dose cisplatin every three weeks in primary chemoradiotherapy in head and neck cancer patients with low skeletal muscle mass: The CISLOW-study protocol.

Chemoradiotherapy with cisplatin in a triweekly regimen of 100 mg/m2 body surface area, is used to treat locally advanced head and neck squamous cell carcinoma (HNSCC) with curative intent. Cisplatin dose limiting toxicity (CDLT) occurs often and impedes obtaining the planned cumulative cisplatin dose. A cumulative cisplatin dose of 200 mg/m2 or more is warranted for better survival and locoregional control. Patients with a low skeletal muscle mass (SMM) have a three-fold higher risk of developing CDLT than patients with a normal SMM. SMM can be assessed through measurements on routinely performed diagnostic head and neck CT- or MRI-scans. A weekly regimen of 40 mg/m2 body surface area cisplatin is proposed as a less toxic schedule, which possibly decreases the risk of developing CDLT and enables reaching a higher cumulative cisplatin dose. The aim of this multicenter randomized clinical trial (NL76533.041.21, registered in the Netherlands Trial Register) is to identify whether a regimen of weekly cisplatin increases compliance to the planned chemotherapy scheme in HNSCC patients with low SMM. The primary outcome is the difference in compliance rate, defined as absence of CDLT, between low SMM patients receiving either the weekly or triweekly regimen. Secondary outcomes consist of toxicities, the cumulative cisplatin dose, time to recurrence, incidence of recurrence at two years of follow-up, location of recurrence, 2-year overall, disease free and disease specific survival, quality of life, patient's experiences, and cost-effectiveness.

Ultrasound-guided resection for squamous cell carcinoma of the buccal mucosa: A feasibility study.

BACKGROUND: Image-guided surgery could help obtain clear (≥5.0 mm) resection margins. This feasibility study investigated ultrasound-guided resection accuracy of buccal mucosa squamous cell carcinoma (BMSCC). METHODS: MRI and ultrasound measurements of tumor thickness were compared to histology in 13 BMSCC-patients. Ultrasound measured margins (at five locations) on the specimen were compared to the corresponding histological margins. RESULTS: Accuracy of in- and ex-vivo ultrasound (mean deviation from histology: 1.6 mm) for measuring tumor thickness was comparable to MRI (mean deviation from histology: 2.6 mm). The sensitivity to detect clear margins using ex-vivo ultrasound was low (48%). If an ex-vivo ultrasound cutoff of ≥7.5 mm would be used, the sensitivity would increase to 86%. CONCLUSIONS: Ultrasound-guided resection of BMSCC's is feasible. In- and ex-vivo ultrasound measure tumor thickness in BMSCC accurately. We recommend ≥7.5 mm resection margins on ex-vivo ultrasound to obtain histological clear margins. Additional research is required to establish the effect of 7.5 mm ultrasound cutoff.

Collateral status and recanalization after endovascular treatment for acute ischemic stroke.

BACKGROUND: Successful recanalization and good collateral status are associated with good clinical outcomes after endovascular treatment (EVT) for acute ischemic stroke, but the relationships among them are unclear. OBJECTIVE: To assess if collateral status is associated with recanalization after EVT and if collateral status modifies the association between successful recanalization and functional outcome. METHODS: We retrospectively analyzed data from the MR CLEAN Registry, a multicenter prospective cohort study of patients with a proximal anterior occlusion who underwent EVT in the Netherlands. We determined collateral status with a previously validated four-point visual grading scale and defined successful recanalization as an extended Thrombolysis in Cerebral Infarction score ≥2B. Functional outcome was determined using the modified Rankin Scale score at 90 days. We assessed, with multivariable logistic regression models, the associations between (1) collateral status and successful recanalization, (2) successful recanalization and functional outcome, (3) collateral status and functional outcome. An interaction of collateral status and successful recanalization was assessed. Subgroup analyses were performed for patients treated with intravenous thrombolysis. RESULTS: We included 2717 patients, of whom 1898 (70%) had successful recanalization. There was no relationship between collateral status and successful recanalization (adjusted common OR (95% CI) of grades 1, 2, and 3 vs 0: 1.19 (0.82 to 1.72), 1.20 (0.83 to 1.75), and 1.10 (0.74 to 1.63), respectively). Successful recanalization (acOR (95% CI): 2.15 (1.84 to 2.52)) and better collateral grades (acOR (95% CI) of grades 1, 2, and 3 vs 0: 2.12 (1.47 to 3.05), 3.46 (2.43 to 4.92), and 4.16 (2.89 to 5.99), respectively) were both associated with a shift towards better functional outcome, without an interaction between collateral status and successful recanalization. Results were similar for the subgroup of thrombolysed patients. CONCLUSIONS: Collateral status is not associated with the probability of successful recanalization after EVT and does not modify the association between successful recanalization and functional outcome.

Synthetic MRI with Magnetic Resonance Spin TomogrAphy in Time-Domain (MR-STAT): Results from a Prospective Cross-Sectional Clinical Trial.

BACKGROUND: Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) can reconstruct whole-brain multi-parametric quantitative maps (eg, T1 , T2 ) from a 5-minute MR acquisition. These quantitative maps can be leveraged for synthetization of clinical image contrasts. PURPOSE: The objective was to assess image quality and overall diagnostic accuracy of synthetic MR-STAT contrasts compared to conventional contrast-weighted images. STUDY TYPE: Prospective cross-sectional clinical trial. POPULATION: Fifty participants with a median age of 45 years (range: 21-79 years) consisting of 10 healthy participants and 40 patients with neurological diseases (brain tumor, epilepsy, multiple sclerosis or stroke). FIELD STRENGTH/SEQUENCE: 3T/Conventional contrast-weighted imaging (T1 /T2 weighted, proton density [PD] weighted, and fluid-attenuated inversion recovery [FLAIR]) and a MR-STAT acquisition (2D Cartesian spoiled gradient echo with varying flip angle preceded by a non-selective inversion pulse). ASSESSMENT: Quantitative T1 , T2 , and PD maps were computed from the MR-STAT acquisition, from which synthetic contrasts were generated. Three neuroradiologists blinded for image type and disease randomly and independently evaluated synthetic and conventional datasets for image quality and diagnostic accuracy, which was assessed by comparison with the clinically confirmed diagnosis. STATISTICAL TESTS: Image quality and consequent acceptability for diagnostic use was assessed with a McNemar's test (one-sided α = 0.025). Wilcoxon signed rank test with a one-sided α = 0.025 and a margin of Δ = 0.5 on the 5-level Likert scale was used to assess non-inferiority. RESULTS: All data sets were similar in acceptability for diagnostic use (≥3 Likert-scale) between techniques (T1 w:P = 0.105, PDw:P = 1.000, FLAIR:P = 0.564). However, only the synthetic MR-STAT T2 weighted images were significantly non-inferior to their conventional counterpart; all other synthetic datasets were inferior (T1 w:P = 0.260, PDw:P = 1.000, FLAIR:P = 1.000). Moreover, true positive/negative rates were similar between techniques (conventional: 88%, MR-STAT: 84%). DATA CONCLUSION: MR-STAT is a quantitative technique that may provide radiologists with clinically useful synthetic contrast images within substantially reduced scan time. EVIDENCE LEVEL: 1 Technical Efficacy: Stage 2.

Occurrence, Risk Factors, and Consequences of Postoperative Ischemia After Glioma Resection: A Retrospective Study.

BACKGROUND: Postoperative ischemia can lead to neurological deficits and is a known complication of glioma resection. There is inconsistency in documented incidence of ischemia after glioma resection, and the precise cause of ischemia is often unknown. OBJECTIVE: To assess the incidence of postoperative ischemia and neurological deficits after glioma resection and to evaluate their association with potential risk factors. METHODS: One hundred thirty-nine patients with 144 surgeries between January 2012 and September 2014 for World Health Organization (WHO) 2016 grade II-IV diffuse supratentorial gliomas with postoperative MRI within 72 hours were retrospectively included. Patient, tumor, and perioperative data were extracted from the electronic patient records. Occurrence of postoperative confluent ischemia, defined as new confluent areas of diffusion restriction, and new or worsened neurological deficits were analyzed univariably and multivariably using logistic regression models. RESULTS: Postoperative confluent ischemia was found in 64.6% of the cases. Occurrence of confluent ischemia was associated with an insular location ( P = .042) and intraoperative administration of vasopressors ( P = .024) in multivariable analysis. Glioma location in the temporal lobe was related to an absence of confluent ischemia ( P = .01). Any new or worsened neurological deficits occurred in 30.6% and 20.9% at discharge from the hospital and at first follow-up, respectively. Occurrence of ischemia was significantly associated with the presence of novel neurological deficits at discharge ( P = .013) and after 3 months ( P = .024). CONCLUSION: Postoperative ischemia and neurological deficit were significantly correlated. Intraoperative administration of vasopressors, insular glioma involvement, and absence of temporal lobe involvement were significantly associated with postoperative ischemia.

The spatial relationship between the MRI lesion and intraoperative electrocorticography in focal epilepsy surgery.

MRI and intraoperative electrocorticography are often used in tandem to delineate epileptogenic tissue in resective surgery for focal epilepsy. Both the resection of the MRI lesion and tissue with high rates of electrographic discharges on electrocorticography, e.g. spikes and high-frequency oscillations (80-500 Hz), lead to a better surgical outcome. How MRI and electrographic markers are related, however, is currently unknown. The aim of this study was to find the spatial relationship between MRI lesions and spikes/high-frequency oscillations. We retrospectively included 33 paediatric and adult patients with lesional neocortical epilepsy who underwent electrocorticography-tailored surgery (14 females, median age = 13.4 years, range = 0.6-47.0 years). Mesiotemporal lesions were excluded. We used univariable linear regression to find correlations between pre-resection spike/high-frequency oscillation rates on an electrode and its distance to the MRI lesion. We tested straight lines to the centre and the edge of the MRI lesion, and the distance along the cortical surface to determine which of these distances best reflects the occurrence of spikes/high-frequency oscillations. We conducted a moderator analysis to investigate the influence of the underlying pathology type and lesion volume on our results. We found spike and high-frequency oscillation rates to be spatially linked to the edge of the MRI lesion. The underlying pathology type influenced the spatial relationship between spike/high-frequency oscillation rates and the MRI lesion (P spikes < 0.0001, P ripples < 0.0001), while the lesion volume did not (P spikes = 0.64, P ripples = 0.89). A higher spike rate was associated with a shorter distance to the edge of the lesion for cavernomas [F(1,64) = -1.37, P < 0.0001, η 2 = 0.22], focal cortical dysplasias [F(1,570) = -0.25, P < 0.0001, η 2 = 0.05] and pleomorphic xanthoastrocytomas [F(1,66) = -0.18, P = 0.01, η 2 = 0.09]. In focal cortical dysplasias, a higher ripple rate was associated with a shorter distance [F(1,570) = -0.35, P < 0.0001, η 2 = 0.05]. Conversely, low-grade gliomas showed a positive correlation; the further an electrode was away from the lesion, the higher the rate of spikes [F(1,75) = 0.65, P < 0.0001, η 2 = 0.37] and ripples [F(1,75) = 2.67, P < 0.0001, η 2 = 0.22]. Pathophysiological processes specific to certain pathology types determine the spatial relationship between the MRI lesion and electrocorticography results. In our analyses, non-tumourous lesions (focal cortical dysplasias and cavernomas) seemed to intrinsically generate spikes and high-frequency oscillations, particularly at the border of the lesion. This advocates for a resection of this tissue. Low-grade gliomas caused epileptogenicity in the peritumoural tissue. Whether a resection of this tissue leads to a better outcome is unclear. Our results suggest that the underlying pathology type should be considered when intraoperative electrocorticography is interpreted.

CT Lymphography Using Lipiodol® for Sentinel Lymph Node Biopsy in Early-Stage Oral Cancer.

This study evaluated sentinel lymph node (SLN) identification with CT lymphography (CTL) following peritumoral administration of Lipiodol® relative to conventional 99mTc-nanocolloid lymphoscintigraphy (including SPECT/CT) in 10 early-stage oral cancer patients undergoing SLN biopsy. Patients first underwent early dynamic and static scintigraphy after peritumoral administration of 99mTc-nanocolloid. Subsequently, Lipiodol® was administered at the same injection sites, followed by fluoroscopy and CT acquisition. Finally, late scintigraphy and SPECT/CT were conducted, enabling the fusion of late CTL and SPECT imaging. The next day, designated SLNs were harvested, radiographically examined for Lipiodol® uptake and histopathologically assessed. Corresponding images of CT, 99mTc-nanocolloid lymphoscintigraphy and SPECT/late CTL fusion were evaluated. 99mTc-nanocolloid lymphoscintigraphy identified 21 SLNs, of which 7 were identified with CTL (33%). CTL identified no additional SLNs and failed to identify any SLNs in four patients (40%). Out of six histopathologically positive SLNs, two were identified by CTL (33%). Radiographic examination confirmed Lipiodol® uptake in seven harvested SLNs (24%), of which five were depicted by CTL. CTL using Lipiodol® reached a sensitivity of 50% and a negative predictive value (NPV) of 75% (median follow-up: 12.3 months). These results suggest that CTL using Lipiodol® is not a reliable technique for SLN mapping in early-stage oral cancer.

Slow recruitment in the HIMALAIA study: lessons for future clinical trials in patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on feasibility data.

BACKGROUND: Our randomized clinical trial on induced hypertension in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) was halted prematurely due to unexpected slow recruitment rates. This raised new questions regarding recruitment feasibility. As our trial can therefore be seen as a feasibility trial, we assessed the reasons for the slow recruitment, aiming to facilitate the design of future randomized trials in aSAH patients with DCI or other critically ill patient categories. METHODS: Efficiency of recruitment and factors influencing recruitment were evaluated, based on the patient flow in the two centers that admitted most patients during the study period. We collected numbers of patients who were screened for eligibility, provided informed consent, and developed DCI and who eventually were randomized. RESULTS: Of the 862 aSAH patients admitted in the two centers during the course of the trial, 479 (56%) were eligible for trial participation of whom 404 (84%) were asked for informed consent. Of these, 188 (47%) provided informed consent, of whom 50 (27%) developed DCI. Of these 50 patients, 12 (24%) could not be randomized due to a logistic problem or a contraindication for induced hypertension emerging at the time of randomization, and four (8%) were missed for randomization. Eventually, 34 patients were randomized and received intervention or control treatment. CONCLUSIONS: Enrolling patients in a randomized trial on a treatment strategy for DCI proved unfeasible: only 1 out of 25 admitted and 1 out of 14 eligible patients could eventually be randomized. These rates, caused by a large proportion of ineligible patients, a small proportion of patients providing informed consent, and a large proportion of patients with contraindications for treatment, can be used to make sample size calculations for future randomized trials in DCI or otherwise critically ill patients. Facilitating informed consent through improved provision of information on risks, possible benefits, and study procedures may result in improved enrolment. TRIAL REGISTRATION: The original trial was prospectively registered with ClinicalTrials.gov (NCT01613235), date of registration 07-06-2012.

Cerebral Collateral Circulation in the Era of Reperfusion Therapies for Acute Ischemic Stroke.

Clinical outcomes of patients with acute ischemic stroke depend in part on the extent of their collateral circulation. A good collateral circulation has also been associated with greater benefit of intravenous thrombolysis and endovascular treatment. Treatment decisions for these reperfusion therapies are increasingly guided by a combination of clinical and imaging parameters, particularly in later time windows. Computed tomography and magnetic resonance imaging enable a rapid assessment of both the collateral extent and cerebral perfusion. Yet, the role of the collateral circulation in clinical decision-making is currently limited and may be underappreciated due to the use of rather coarse and rater-dependent grading methods. In this review, we discuss determinants of the collateral circulation in patients with acute ischemic stroke, report on commonly used and emerging neuroimaging techniques for assessing the collateral circulation, and discuss the therapeutic and prognostic implications of the collateral circulation in relation to reperfusion therapies for acute ischemic stroke.

Time Since Stroke Onset, Quantitative Collateral Score, and Functional Outcome After Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: In patients with ischemic stroke undergoing endovascular treatment (EVT), time to treatment and collateral status are important prognostic factors and may be correlated. We aimed to assess the relation between time to CT angiography (CTA) and a quantitatively determined collateral score and to assess whether the collateral score modified the relation between time to recanalization and functional outcome. METHODS: We analyzed data from patients with acute ischemic stroke included in the Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke Registry between 2014 and 2017, who had a carotid terminus or M1 occlusion and were treated with EVT within 6.5 hours of symptom onset. A quantitative collateral score (qCS) was determined from baseline CTA using a validated automated image analysis algorithm. We also determined a 4-point visual collateral score (vCS). Multivariable regression models were used to assess the relations between time to imaging and the qCS and between the time to recanalization and functional outcome (90-day modified Rankin Scale score). An interaction term (time to recanalization × qCS) was entered in the latter model to test whether the qCS modifies this relation. Sensitivity analyses were performed using the vCS. RESULTS: We analyzed 1,813 patients. The median time from symptom onset to CTA was 91 minutes (interquartile range [IQR] 65-150 minutes), and the median qCS was 49% (IQR 25%-78%). Longer time to CTA was not associated with the log-transformed qCS (adjusted ß per 30 minutes, 0.002, 95% CI -0.006 to 0.011). Both a higher qCS (adjusted common odds ratio [acOR] per 10% increase: 1.06, 95% CI 1.03-1.09) and shorter time to recanalization (acOR per 30 minutes: 1.17, 95% CI 1.13-1.22) were independently associated with a shift toward better functional outcome. The qCS did not modify the relation between time to recanalization and functional outcome (p for interaction: 0.28). Results from sensitivity analyses using the vCS were similar. DISCUSSION: In the first 6.5 hours of ischemic stroke caused by carotid terminus or M1 occlusion, the collateral status is unaffected by time to imaging, and the benefit of a shorter time to recanalization is independent of baseline collateral status.

Prevalence, risk factors, and long-term outcomes of cerebral ischemia in hospitalized COVID-19 patients - study rationale and protocol of the CORONIS study: A multicentre prospective cohort study.

Background: COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown. Patients and methods: CORONavirus and Ischemic Stroke (CORONIS) is a multicentre prospective cohort study investigating the prevalence, risk factors and long-term incidence of (silent) cerebral ischemia, and the long-term functional outcome among patients with COVID-19. We aim to include 200 adult patients hospitalized with COVID-19 without symptomatic ischemic stroke to investigate the prevalence of silent cerebral ischemia compared with 60 (matched) controls with MRI. In addition, we will identify potential risk factors and/or causes of cerebral ischemia in COVID-19 patients with (n = 70) or without symptomatic stroke (n = 200) by means of blood sampling, cardiac workup and brain MRI. We will measure functional outcome and cognitive function after 3 and 12 months with standardized questionnaires in all patients with COVID-19. Finally, the long-term incidence of (new) silent cerebral ischemia in patients with COVID-19 will be assessed with follow up MRI (n = 120). Summary: The CORONIS study is designed to add further insight into the prevalence, long-term incidence and risk factors of cerebral ischemia, and the long-term functional outcome in hospitalized adult patients with COVID-19.

Labyrinthine fistulas: Surgical outcomes and an additional diagnostic strategy.

PURPOSE: To evaluate perioperative findings and audiological and vestibular outcomes in patients operated for cholesteatoma with labyrinthine fistulas. Also to assess radiological fistula size. MATERIALS AND METHODS: Patients who underwent surgery for a labyrinthine fistula caused by a cholesteatoma between 2015 and 2020 in a tertiary referral center were retrospectively investigated. Fistula size was determined on preoperative CT scan. Bone and air conduction pure tone average thresholds were obtained pre- and postoperatively. Clinical outcomes, such as vertigo and otorrea were also evaluated. Main purpose was to determine whether there is a correlation between fistula size and postoperative hearing. Furthermore, perioperative findings and vestibular outcomes are evaluated. RESULTS: 21 patients (22 cases) with a labyrinthine fistula were included. There was no significant change after surgery in bone conduction pure tone average (preoperatively 27.6 dB ± 26.7; postoperatively 30.3 dB ± 34.3; p = 0.628) or air conduction pure tone average (preoperatively 58.7 dB ± 24.3; postoperatively 60.2 dB ± 28.3; p = 0.816). Fistula size was not correlated to postoperative hearing outcome. There were two patients with membranous labyrinth invasion: one patient was deaf preoperatively, the other acquired total sensorineural hearing loss after surgery. CONCLUSIONS: Sensorineural hearing loss after cholesteatoma surgery with labyrinthine fistula is rare. Fistula size and postoperative hearing loss are not correlated, however, membranous labyrinthine invasion seems to be related to poor postoperative hearing outcomes. Therefore, additional preoperative radiological work up, by MRI scan, in selected cases is advocated to guide the surgeon to optimize preoperative counselling.

Conventional MRI Criteria to Differentiate Progressive Disease From Treatment-Induced Effects in High-Grade (WHO Grade 3-4) Gliomas.

BACKGROUND AND OBJECTIVES: Posttreatment radiologic deterioration of an irradiated high-grade (WHO grade 3-4) glioma (HGG) may be the result of true progressive disease or treatment-induced effects (TIE). Differentiation between these entities is of great importance but remains a diagnostic challenge. This study assesses the diagnostic value of conventional MRI characteristics to differentiate progressive disease from TIE in HGGs. METHODS: In this single-center, retrospective, consecutive cohort study, we included adults with a HGG who were treated with (chemo-)radiotherapy and subsequently developed a new or increasing contrast-enhancing lesion on conventional follow-up MRI. TIE and progressive disease were defined radiologically as stable/decreased for ≥6 weeks or Response Assessment in Neuro-Oncology progression and histologically as TIE without viable tumor or progressive disease. Two neuroradiologists assessed 21 preselected MRI characteristics of the progressive lesions. The statistical analysis included logistic regression to develop a full multivariable model, a diagnostic model with model reduction, and a Cohen kappa interrater reliability (IRR) coefficient. RESULTS: A total of 210 patients (median age 61 years, interquartile range 54-68, 189 male) with 284 lesions were included, of whom 141 (50%) had progressive disease. Median time to progressive disease was 2 (0.7-6.1) and to TIE 0.9 (0.7-3.5) months after radiotherapy. After multivariable modeling and model reduction, the following determinants prevailed: radiation dose (odds ratio [OR] 0.68, 95% CI 0.49-0.93), longer time to progression (TTP; OR 3.56, 95% CI 1.84-6.88), marginal enhancement (OR 2.04, 95% CI 1.09-3.83), soap bubble enhancement (OR 2.63, 95% CI 1.39-4.98), and isointense apparent diffusion coefficient (ADC) signal (OR 2.11, 95% CI 1.05-4.24). ORs >1 indicate higher odds of progressive disease. The Hosmer & Lemeshow test showed good calibration (p = 0.947) and the area under the receiver operating characteristic curve was 0.722 (95% CI 0.66-0.78). In the glioblastoma subgroup, TTP, marginal enhancement, and ADC signal were significant. IRR analysis between neuroradiologists revealed moderate to near perfect agreement for the predictive items but poor agreement for others. DISCUSSION: Several characteristics from conventional MRI are significant predictors for the discrimination between progressive disease and TIE. However, IRR was variable. Conventional MRI characteristics from this study should be incorporated into a multimodal diagnostic model with advanced imaging techniques. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with irradiated HGGs, radiation dose, longer TTP, marginal enhancement, soap bubble enhancement, and isointense ADC signal distinguish progressive disease from TIE.

Masseter muscle parameters can function as an alternative for skeletal muscle mass assessments on cross-sectional imaging at lumbar or cervical vertebral levels.

BACKGROUND: Patients with head and neck cancer are at increased risk of developing low skeletal muscle mass (SMM), which is associated with adverse treatment outcomes and prognosis. Low SMM is most commonly assessed by the skeletal muscle cross sectional area (CSA) at the third lumbar vertebra (L3) or more recently the third cervical vertebra (C3). L3 is not routinely imaged and C3 may be impacted by disease or treatment. As an alternative we analyzed masseter muscle characteristics and their relationship with L3 and C3 skeletal muscle CSA and overall survival (OS). METHODS: In this single-center retrospective study, 99 patients with head and neck cancer who underwent whole body FDG-PET/CT-scans were reviewed. Of these patients, L3 CSA, C3 CSA, masseter CSA, masseter thickness, masseter volume, masseter Hounsfield Unit values, lumbar skeletal muscle index (LSMI), cervical skeletal muscle index (CSMI), and masseter skeletal muscle index (MSMI) were recorded and correlated with each other and with OS. RESULTS: We included 72 male and 27 female patients. The masseter muscle parameters differed significantly between sexes. The Spearman correlation coefficients for C3 CSA-Masseter volume and L3 CSA-Masseter volume were 0.639 and 0.531 (P<0.001) respectively. In multivariate analysis low MSMI was a predictor of OS (HR 2.227, P=0.009). CONCLUSIONS: There is a moderate to strong association between the masseter muscle volume (MV) and C3 CSA and L3 CSA. MSMI predicts OS. Further research should investigate the relationship between muscle function and masseter muscle parameters and impacting factors on masseter muscle dimensions.