Publications by authors named "Sean Symons"

100 Publications

nnResting state fMRI scanner instabilities revealed by longitud inal phantom scans in a multi-center study.

Neuroimage 2021 May 21;237:118197. Epub 2021 May 21.

Rotman Research Institute, University of Toronto, Toronto, ON, Canada; Medical Biophysics, University of Toronto, Toronto, ON, Canada. Electronic address:

Quality assurance (QA) is crucial in longitudinal and/or multi-site studies, which involve the collection of data from a group of subjects over time and/or at different locations. It is important to regularly monitor the performance of the scanners over time and at different locations to detect and control for intrinsic differences (e.g., due to manufacturers) and changes in scanner performance (e.g., due to gradual component aging, software and/or hardware upgrades, etc.). As part of the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Canadian Biomarker Integration Network in Depression (CAN-BIND), QA phantom scans were conducted approximately monthly for three to four years at 13 sites across Canada with 3T research MRI scanners. QA parameters were calculated for each scan using the functional Biomarker Imaging Research Network's (fBIRN) QA phantom and pipeline to capture between- and within-scanner variability. We also describe a QA protocol to measure the full-width-at-half-maximum (FWHM) of slice-wise point spread functions (PSF), used in conjunction with the fBIRN QA parameters. Variations in image resolution measured by the FWHM are a primary source of variance over time for many sites, as well as between sites and between manufacturers. We also identify an unexpected range of instabilities affecting individual slices in a number of scanners, which may amount to a substantial contribution of unexplained signal variance to their data. Finally, we identify a preliminary preprocessing approach to reduce this variance and/or alleviate the slice anomalies, and in a small human data set show that this change in preprocessing can have a significant impact on seed-based connectivity measurements for some individual subjects. We expect that other fMRI centres will find this approach to identifying and controlling scanner instabilities useful in similar studies.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118197DOI Listing
May 2021

MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease.

Sleep Med 2021 Apr 19;83:83-88. Epub 2021 Apr 19.

Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, ON, Canada.

Objectives: Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior.

Methods: We analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index.

Results: Individuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38-22.26, p = 0.018).

Conclusions: Individuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.
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http://dx.doi.org/10.1016/j.sleep.2021.03.043DOI Listing
April 2021

In vivo detection of beta-amyloid at the nasal cavity and other skull-base sites: a retrospective evaluation of ADNI1/GO.

Ann Nucl Med 2021 Jun 12;35(6):728-734. Epub 2021 Apr 12.

Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, M4N 3M5, Canada.

Introduction: Amyloid beta (Aβ) is partially cleared from the CSF via skull base perivascular and perineural lymphatic pathways, particularly at the nasal cavity. In vivo differences in Aβ level at the nasal cavity between patients with Alzheimer's disease (AD), subjects with mild cognitive impairment (MCI) and cognitively normal (CN) individuals have not been previously assessed.

Methods: This is a retrospective evaluation of subject level data from the ADNI-1/GO database. Standardized uptake value ratio (SUVR) maximum on C-Pittsburgh compound-B (PiB)-PET was assessed at the nasal cavity on 223 scans. Exploratory ROI analysis was also performed at other skull base sites. SUVR maximum values and their differences between groups (CN, MCI, AD) were assessed. CSF Aβ levels and CSF Aβ 42/40 ratios were correlated with SUVR maximum values.

Results: 103 subjects with 223 PiB-PET scans (47 CN, 32 AD and 144 MCI) were included in the study. The SUVR maxima at the nasal cavity were significantly lower in subjects with AD [1.35 (± 0.31)] compared to CN [1.54 (± 0.30); p = 0.024] and MCI [1.49 (± 0.33); p = 0.049]. At very low CSF Aβ, less than 132 pg/ml, there was significant correlation with nasal cavity SUVR maximum. The summed averaged SUVR maximum values were significantly lower in subjects with AD [1.35 (± 0.16)] compared to CN [1.49 (± 0.17); p = 0.003] and MCI [1.40 (± 0.17); p = 0.017].

Conclusion: Patients with AD demonstrate reduced nasal cavity PiB-PET radiotracer uptake compared to MCI and CN, possibly representing reduced Aβ clearance via perineural/perivascular lymphatic pathway. Further work is necessary to elucidate the true nature of this finding.
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http://dx.doi.org/10.1007/s12149-021-01614-7DOI Listing
June 2021

Multisite Comparison of MRI Defacing Software Across Multiple Cohorts.

Front Psychiatry 2021 24;12:617997. Epub 2021 Feb 24.

Rotman Research Institute, Baycrest Health Sciences Centre, Toronto, ON, Canada.

With improvements to both scan quality and facial recognition software, there is an increased risk of participants being identified by a 3D render of their structural neuroimaging scans, even when all other personal information has been removed. To prevent this, facial features should be removed before data are shared or openly released, but while there are several publicly available software algorithms to do this, there has been no comprehensive review of their accuracy within the general population. To address this, we tested multiple algorithms on 300 scans from three neuroscience research projects, funded in part by the Ontario Brain Institute, to cover a wide range of ages (3-85 years) and multiple patient cohorts. While skull stripping is more thorough at removing identifiable features, we focused mainly on defacing software, as skull stripping also removes potentially useful information, which may be required for future analyses. We tested six publicly available algorithms (afni_refacer, deepdefacer, mri_deface, mridefacer, pydeface, quickshear), with one skull stripper (FreeSurfer) included for comparison. Accuracy was measured through a pass/fail system with two criteria; one, that all facial features had been removed and two, that no brain tissue was removed in the process. A subset of defaced scans were also run through several preprocessing pipelines to ensure that none of the algorithms would alter the resulting outputs. We found that the success rates varied strongly between defacers, with afni_refacer (89%) and pydeface (83%) having the highest rates, overall. In both cases, the primary source of failure came from a single dataset that the defacer appeared to struggle with - the youngest cohort (3-20 years) for afni_refacer and the oldest (44-85 years) for pydeface, demonstrating that defacer performance not only depends on the data provided, but that this effect varies between algorithms. While there were some very minor differences between the preprocessing results for defaced and original scans, none of these were significant and were within the range of variation between using different NIfTI converters, or using raw DICOM files.
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http://dx.doi.org/10.3389/fpsyt.2021.617997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943842PMC
February 2021

Low Doses of Ionizing Radiation as a Treatment for Alzheimer's Disease: A Pilot Study.

J Alzheimers Dis 2021 ;80(3):1119-1128

Baycrest Health Sciences, Toronto, ON, Canada.

Background: In 2015, a patient in hospice with Alzheimer's disease (AD) was treated with ionizing radiation to her brain using repeated CT scans. Improvement in cognition, speech, movement, and appetite was observed. These improvements were so momentous that she was discharged from the hospice to a long-term care home. Based on this case, we conducted a pilot clinical trial to examine the effect of low-dose ionizing radiation (LDIR) in severe AD.

Objective: To determine whether the previously reported benefits of LDIR in a single case with AD could be observed again in other cases with AD when the same treatments are given.

Methods: In this single-arm study, four patients were treated with three consecutive treatments of LDIR, each spaced two weeks apart. Qualitative changes in communication and behavior with close relatives were observed and recorded. Quantitative measures of cognition and behavior were administered pre and post LDIR treatments.

Results: Minor improvements on quantitative measures were noted in three of the four patients following treatment. However, the qualitative observations of cognition and behavior suggested remarkable improvements within days post-treatment, including greater overall alertness. One patient showed no change.

Conclusion: LDIR may be a promising, albeit controversial therapy for AD. Trials of patients with less severe AD, double-blind and placebo-controlled, should be carried out to determine the benefits of LDIR. Quantitative measures are needed that are sensitive to the remarkable changes induced by LDIR, such as biological markers of oxidative stress that are associated with AD.
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http://dx.doi.org/10.3233/JAD-200620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150498PMC
January 2021

Improved Segmentation of the Intracranial and Ventricular Volumes in Populations with Cerebrovascular Lesions and Atrophy Using 3D CNNs.

Neuroinformatics 2021 Feb 1. Epub 2021 Feb 1.

Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N = 528 subjects for ICV, N = 501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches. The models were tested on 238 participants, including subjects with vascular cognitive impairment and high white matter hyperintensity burden. Two of the three test sets came from studies not used in the training dataset. We assessed our algorithms relative to four state-of-the-art ICV extraction methods (MONSTR, BET, Deep Extraction, FreeSurfer, DeepMedic), as well as two ventricular segmentation tools (FreeSurfer, DeepMedic). Our multi-contrast models outperformed other methods across many of the evaluation metrics, with average Dice coefficients of 0.98 and 0.96 for ICV and ventricular segmentation respectively. Both models were also the most time efficient, segmenting the structures in orders of magnitude faster than some of the other available methods. Our networks showed an increased accuracy with the use of a conditional random field (CRF) as a post-processing step. We further validated both segmentation models, highlighting their robustness to images with lower resolution and signal-to-noise ratio, compared to tested techniques. The pipeline and models are available at: https://icvmapp3r.readthedocs.io and https://ventmapp3r.readthedocs.io to enable further investigation of the roles of ICV and ventricles in relation to normal aging and neurodegeneration in large multi-site studies.
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http://dx.doi.org/10.1007/s12021-021-09510-1DOI Listing
February 2021

Diagnostic Neuroradiology Subspecialty Training: 1 Versus 2 Years; the Canadian Perspective.

Can Assoc Radiol J 2021 Jan 18:846537120982984. Epub 2021 Jan 18.

Department of Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia, Canada.

Background: Canada began a national reform of its post-graduate medical education training programs to a Competence By Design (CBD) model. Trends from accredited neuroradiology programs from the past 10 years were investigated to inform educators and stakeholders for this process.

Methods: A 13-question electronic survey was sent to program directors of all 8 accredited neuroradiology training programs in Canada. Data was requested for each year on the 2008-2019 graduating classes. Questions pertained to program enrolment; program completion; post-training employment; and the sufficiency of 1-year training programs.

Results: Response rate was 100%. Over the timeframe studied, the 2-year programs increased in size ( = 0.007), while the 1-year programs remained steady ( = 0.27). 12.2% of trainees enrolled in the 2-year program dropped out after 1 year, and were considered 1-year trainees thereafter. A higher proportion of 2-year trainees obtain positions within academic institutions (89.5 vs 67.2%, = 0.0007), whereas a higher proportion of 1-year trainees obtain positions within non-academic institutions (29.3 vs 8.1%, = 0.0007). A higher proportion of those with Canadian board certification in diagnostic radiology who completed a 2-year program obtained a position within a Canadian academic institution compared to non-certified 2-year trainees ( < 0.001). 71.4% of program directors agreed that a 1-year program was sufficient for non-academic staff positions.

Conclusion: The length of the training program has significant impact on employment in academic vs non-academic institutions. This information can be used to guide the upcoming CBD initiative for neuroradiology programs.
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http://dx.doi.org/10.1177/0846537120982984DOI Listing
January 2021

Cortical Thickness Estimation in Individuals With Cerebral Small Vessel Disease, Focal Atrophy, and Chronic Stroke Lesions.

Front Neurosci 2020 14;14:598868. Epub 2020 Dec 14.

LC Campbell Cognitive Neurology Research, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.

Background: Regional changes to cortical thickness in individuals with neurodegenerative and cerebrovascular diseases (CVD) can be estimated using specialized neuroimaging software. However, the presence of cerebral small vessel disease, focal atrophy, and cortico-subcortical stroke lesions, pose significant challenges that increase the likelihood of misclassification errors and segmentation failures.

Purpose: The main goal of this study was to examine a correction procedure developed for enhancing FreeSurfer's (FS's) cortical thickness estimation tool, particularly when applied to the most challenging MRI obtained from participants with chronic stroke and CVD, with varying degrees of neurovascular lesions and brain atrophy.

Methods: In 155 CVD participants enrolled in the Ontario Neurodegenerative Disease Research Initiative (ONDRI), FS outputs were compared between a fully automated, unmodified procedure and a corrected procedure that accounted for potential sources of error due to atrophy and neurovascular lesions. Quality control (QC) measures were obtained from both procedures. Association between cortical thickness and global cognitive status as assessed by the Montreal Cognitive Assessment (MoCA) score was also investigated from both procedures.

Results: Corrected procedures increased "Acceptable" QC ratings from 18 to 76% for the cortical ribbon and from 38 to 92% for tissue segmentation. Corrected procedures reduced "Fail" ratings from 11 to 0% for the cortical ribbon and 62 to 8% for tissue segmentation. FS-based segmentation of T1-weighted white matter hypointensities were significantly greater in the corrected procedure (5.8 mL vs. 15.9 mL, < 0.001). The unmodified procedure yielded no significant associations with global cognitive status, whereas the corrected procedure yielded positive associations between MoCA total score and clusters of cortical thickness in the left superior parietal ( = 0.018) and left insula ( = 0.04) regions. Further analyses with the corrected cortical thickness results and MoCA subscores showed a positive association between left superior parietal cortical thickness and Attention ( < 0.001).

Conclusion: These findings suggest that correction procedures which account for brain atrophy and neurovascular lesions can significantly improve FS's segmentation results and reduce failure rates, thus maximizing power by preventing the loss of our important study participants. Future work will examine relationships between cortical thickness, cerebral small vessel disease, and cognitive dysfunction due to neurodegenerative disease in the ONDRI study.
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http://dx.doi.org/10.3389/fnins.2020.598868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768006PMC
December 2020

Corrigendum to "The Effect of Cochlear Size on Cochlear Implantation Outcomes".

Biomed Res Int 2020 1;2020:6407456. Epub 2020 Oct 1.

Sunnybrook Health Sciences Centre, Toronto, Canada M4N 3M5.

[This corrects the article DOI: 10.1155/2019/5849871.].
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http://dx.doi.org/10.1155/2020/6407456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556065PMC
October 2020

Ontario Neurodegenerative Disease Research Initiative (ONDRI): Structural MRI Methods and Outcome Measures.

Front Neurol 2020 11;11:847. Epub 2020 Aug 11.

Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.

The Ontario Neurodegenerative Research Initiative (ONDRI) is a 3 years multi-site prospective cohort study that has acquired comprehensive multiple assessment platform data, including 3T structural MRI, from neurodegenerative patients with Alzheimer's disease, mild cognitive impairment, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and cerebrovascular disease. This heterogeneous cross-section of patients with complex neurodegenerative and neurovascular pathologies pose significant challenges for standard neuroimaging tools. To effectively quantify regional measures of normal and pathological brain tissue volumes, the ONDRI neuroimaging platform implemented a semi-automated MRI processing pipeline that was able to address many of the challenges resulting from this heterogeneity. The purpose of this paper is to serve as a reference and conceptual overview of the comprehensive neuroimaging pipeline used to generate regional brain tissue volumes and neurovascular marker data that will be made publicly available online.
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http://dx.doi.org/10.3389/fneur.2020.00847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431907PMC
August 2020

Parkinson's Disease, NOTCH3 Genetic Variants, and White Matter Hyperintensities.

Mov Disord 2020 11 23;35(11):2090-2095. Epub 2020 Jun 23.

Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada.

Background: White matter hyperintensities (WMH) on magnetic resonance imaging may influence clinical presentation in patients with Parkinson's disease (PD), although their significance and pathophysiological origins remain unresolved. Studies examining WMH have identified pathogenic variants in NOTCH3 as an underlying cause of inherited forms of cerebral small vessel disease.

Methods: We examined NOTCH3 variants, WMH volumes, and clinical correlates in 139 PD patients in the Ontario Neurodegenerative Disease Research Initiative cohort.

Results: We identified 13 PD patients (~9%) with rare (<1% of general population), nonsynonymous NOTCH3 variants. Bayesian linear modeling demonstrated a doubling of WMH between variant negative and positive patients (3.1 vs. 6.9 mL), with large effect sizes for periventricular WMH (d = 0.8) and lacunes (d = 1.2). Negative correlations were observed between WMH and global cognition (r = -0.2).

Conclusion: The NOTCH3 rare variants in PD may significantly contribute to increased WMH burden, which in turn may negatively influence cognition. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28171DOI Listing
November 2020

Structural Brain Magnetic Resonance Imaging to Rule Out Comorbid Pathology in the Assessment of Alzheimer's Disease Dementia: Findings from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study and Clinical Trials Over the Past 10 Years.

J Alzheimers Dis 2020 ;74(3):747-757

Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Background/objective: Structural brain magnetic resonance imaging (MRI) is not mandatory in Alzheimer's disease (AD) research or clinical guidelines. We aimed to explore the use of structural brain MRI in AD/mild cognitive impairment (MCI) trials over the past 10 years and determine the frequency with which inclusion of standardized structural MRI acquisitions detects comorbid vascular and non-vascular pathologies.

Methods: We systematically searched ClinicalTrials.gov for AD clinical trials to determine their neuroimaging criteria and then used data from an AD/MCI cohort who underwent standardized MRI protocols, to determine type and incidence of clinically relevant comorbid pathologies.

Results: Of 210 AD clinical trials, 105 (50%) included structural brain imaging in their eligibility criteria. Only 58 (27.6%) required MRI. 16,479 of 53,755 (30.7%) AD participants were in trials requiring MRI. In the observational AD/MCI cohort, 141 patients met clinical criteria; 22 (15.6%) had relevant MRI findings, of which 15 (10.6%) were exclusionary for the study.

Discussion: In AD clinical trials over the last 10 years, over two-thirds of participants could have been enrolled without brain MRI and half without even a brain CT. In a study sample, relevant comorbid pathology was found in 15% of participants, despite careful screening. Standardized structural MRI should be incorporated into NIA-AA diagnostic guidelines (when available) and research frameworks routinely to reduce diagnostic heterogeneity.
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http://dx.doi.org/10.3233/JAD-191097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242844PMC
April 2021

Comparison of quality control methods for automated diffusion tensor imaging analysis pipelines.

PLoS One 2019 20;14(12):e0226715. Epub 2019 Dec 20.

Centre for Functional and Metabolic Mapping, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

The processing of brain diffusion tensor imaging (DTI) data for large cohort studies requires fully automatic pipelines to perform quality control (QC) and artifact/outlier removal procedures on the raw DTI data prior to calculation of diffusion parameters. In this study, three automatic DTI processing pipelines, each complying with the general ENIGMA framework, were designed by uniquely combining multiple image processing software tools. Different QC procedures based on the RESTORE algorithm, the DTIPrep protocol, and a combination of both methods were compared using simulated ground truth and artifact containing DTI datasets modeling eddy current induced distortions, various levels of motion artifacts, and thermal noise. Variability was also examined in 20 DTI datasets acquired in subjects with vascular cognitive impairment (VCI) from the multi-site Ontario Neurodegenerative Disease Research Initiative (ONDRI). The mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated in global brain grey matter (GM) and white matter (WM) regions. For the simulated DTI datasets, the measure used to evaluate the performance of the pipelines was the normalized difference between the mean DTI metrics measured in GM and WM regions and the corresponding ground truth DTI value. The performance of the proposed pipelines was very similar, particularly in FA measurements. However, the pipeline based on the RESTORE algorithm was the most accurate when analyzing the artifact containing DTI datasets. The pipeline that combined the DTIPrep protocol and the RESTORE algorithm produced the lowest standard deviation in FA measurements in normal appearing WM across subjects. We concluded that this pipeline was the most robust and is preferred for automated analysis of multisite brain DTI data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226715PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924651PMC
April 2020

The Effect of Cochlear Size on Cochlear Implantation Outcomes.

Biomed Res Int 2019 4;2019:5849871. Epub 2019 Jun 4.

Sunnybrook Health Sciences Centre, Toronto M4N3M5, Canada.

Objectives: To determine if cochlear duct length and cochlear basal diameter, measured using routinely available radiology software, affect hearing outcomes after cochlear implantation with two different length electrodes.

Methods: 55 patients who received a Med-El Flex electrode were retrospectively reviewed. 34 patients received the Flex 31 electrode (31mm) and 21 patients received the Flex 28 electrode (28mm). Preoperative high-resolution CT scans of the temporal bone were reformatted in the axial and coronal plane. The basal diameter of the cochlear (A-value) and the outer-wall lengths of the cochlear duct were measured using readily available imaging software. Postoperative plane X-rays were used to determine the degree of electrode insertion and the number of electrodes within the cochlea and speech discrimination scores at 6 months were evaluated.

Results: The cochlear metrics obtained were comparable with those previously published in the literature. There was no significant difference in the degree of insertion or speech outcomes between the two electrode lengths. However, when the group who had received the shorter electrode were analysed, there was an association seen between both cochlear duct length and cochlear diameter and speech outcomes.

Conclusions: Cochlear size may be a factor in determining speech outcomes that cannot be explained solely by insertion depth or degrees of insertion. Further studies are required to determine if cochlear duct length is an independent predictor of speech outcomes.
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http://dx.doi.org/10.1155/2019/5849871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582906PMC
January 2020

Incidence of Dural Venous Sinus Thrombosis in Patients with Glioblastoma and Its Implications.

World Neurosurg 2019 05 24;125:e189-e197. Epub 2019 Jan 24.

Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objective: Glioblastoma (GBM) is associated with increased risk of developing dural venous sinus thrombosis (DVST), which often goes undiagnosed as symptoms are readily attributed to tumor. The purpose of this study was to investigate the incidence of DVST, potential predictive features on imaging, complications, its effect on survival, and time of greatest risk for developing DVST.

Methods: A retrospective search of patients with GBM who had surgery followed by chemotherapy and/or radiation therapy between 2009 and 2015 at our institution was performed. Magnetic resonance imaging studies of the brain were reviewed on volumetric postgadolinium T1-weighted sequences for DVST. Tumors were characterized using the Visually Accessible REMBRANDT (Repository for Molecular Brain Neoplasia Data) Images classification, and identified thromboses were tracked for propagation, regression, or resolution. Statistical analyses were directed at identifying clinical predictors and survival differences between the DVST and no-DVST groups.

Results: In total, 163 cases totaling 1637 scans, were reviewed; 12 patients (7.4%) developed DVST, of whom 11 presented with thrombus before any treatment. Tumor invasion of dural sinuses and greater T1/fluid-attenuated inversion recovery ratios were significantly associated with thrombus development (P = 0.02 and P = 0.02, respectively). In patients who developed DVST, thrombosis was more likely to develop ipsilateral to tumor side (P = 0.01) and was associated with a greater likelihood of developing extracranial venous thromboembolism (P = 0.012). There were no venous infarcts and no significant difference in survival between groups (P = 0.83).

Conclusions: Patients with GBM have increased risk of developing DVST, independent of surgical treatment or chemoradiation. DVST presence does not affect survival. Tumor invasion of dural sinuses and greater T1/fluid-attenuated inversion recovery ratio on preoperative imaging were the most significant predictors of DVST development.
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http://dx.doi.org/10.1016/j.wneu.2019.01.039DOI Listing
May 2019

Effectiveness of skull X-RAY to determine cochlear implant insertion depth.

J Otolaryngol Head Neck Surg 2018 Sep 3;47(1):50. Epub 2018 Sep 3.

Division of Otolaryngology - Head and Neck Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.

Background: Cochlear implant (CI) insertion depth can affect residual hearing preservation, tonotopic range coverage, and Mapping. Therefore, determining insertion depth has the potential to maximize CI performance. A post-op skull X-RAY is commonly used to assess insertion depth, however its effectiveness has not been well established. Our primary objective was to assess the accuracy of post-op skull X-RAYs to determine insertion depth, compared to CT as the gold standard. Secondary objectives were to compare experience level of raters and different skull X-RAY views.

Methods: Thirteen patients with Advanced Bionic HiRes 90 K implants, and post-operative temporal bone CT scans were selected from the CI database at Sunnybrook Health Sciences Centre. Medical students, otology fellows, and CI surgeons evaluated insertion depths on post-op skull X-RAYs, while neuroradiologists evaluated CT scans. Descriptive statistics, regression analysis, and paired t-tests were used to compare the two types of imaging.

Results: X-RAYs and CTs provided an equivalent mean insertion depth of 337 degrees (p = 0.93), a mean difference of - 0.9 degrees and a standard deviation of paired differences of 43 degrees. Although means were similar across rater groups, CI surgeons (45 degrees) had the lowest standard deviation of paired differences. Comparing X-RAY views, Caldwell (29 degrees) had less variation than Towne (59 degrees) for standard deviation of paired differences.

Conclusions: Skull X-RAYs provide accurate and reliable measurements for CI insertion depth. The Caldwell view alone may be sufficient for evaluations of insertion depth, and experience has a minor impact on the variability of estimates.
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http://dx.doi.org/10.1186/s40463-018-0304-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122652PMC
September 2018

Imaging the Unconscious "Found Down" Patient in the Emergency Department.

Neuroimaging Clin N Am 2018 Aug 8;28(3):435-451. Epub 2018 Jun 8.

Department of Radiology, University of Ottawa, The Ottawa Hospital, Civic and General Campus, 1053 Carling Avenue, Ottawa, ON K1Y 4E9, Canada.

Unconsciousness may be due to severe brain damage or to potentially reversible causes. Noncontrast head computed tomography (CT) helps identify acute ischemic and hemorrhagic lesions as well as certain patterns of toxic encephalopathy. MR imaging plays an important role in the assessment of acutely encephalopathic patients who may show no significant abnormality on CT. This review describes some of the common and infrequent entities that can lead to unconsciousness, including epilepsy and vascular, traumatic, metabolic, and toxic disorders.
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http://dx.doi.org/10.1016/j.nic.2018.03.006DOI Listing
August 2018

Hypoxia Detection in Infiltrative Astrocytoma: Ferumoxytol-based Quantitative BOLD MRI with Intraoperative and Histologic Validation.

Radiology 2018 09 26;288(3):821-829. Epub 2018 Jun 26.

From the Department of Medical Imaging (P.J.M., A.B., S.S., Z.F.D., A.C., P.A.L., O.S., D.M.), Division of Neurosurgery (S.D., T.M., R.J.), Department of Laboratory Medicine and Pathobiology (J.K., D.G.M.), Department of Radiation Oncology (A.S.), Division of Neurology (S.I.), and Department of Biostatistics (E.G.A.), University of Toronto, 263 McCaul St, 4th Floor, Toronto, ON, Canada M5T 1W7; Department of Neurosurgery, Joan C. Edwards School of Medicine, Huntington, WV (N.P.); Department of Mechanical Engineering, Australian College of Kuwait, Kuwait City, Kuwait (A.E.); Department of Physics, Ryerson University, Toronto, Canada (R.J.); and Department of Radiology, Stanford University School of Medicine, Stanford, Calif (G.Z.).

Purpose To validate ferumoxytol-based quantitative blood oxygenation level-dependent (BOLD) MRI for mapping oxygenation of human infiltrative astrocytomas by using intraoperative measurement of tissue oxygen tension and histologic staining. Materials and Methods Fifteen patients with infiltrative astrocytomas were recruited into this prospective multicenter study between July 2014 and December 2016. Prior to treatment, participants underwent preoperative quantitative BOLD MRI with ferumoxytol to generate tissue oxygen saturation (StO) maps. Two intratumoral sites were identified, one with low StO and one with high StO. Neuronavigation was used to locate sites intraoperatively for insertion of oxygen-sensing probes to measure local tissue oxygen tension (PtO). Biopsies from both sites were taken and stained for markers of hypoxia (hypoxia-inducible factor 1α, carbonic anhydrase IX) and neoangiogenesis (vascular endothelial growth factor, endoglin [CD105]). Spearman correlation and nonparametric sign-rank tests were used to analyze data. Results Ten patients with median age of 58.5 years (interquartile range, 25 years; four men and six women) completed the study. Because there is no linear relationship between StO and PtO, the ratios of low to high StO versus low to high PtO in each patient were compared and a significant correlation was found (r = 0.73; P = .01). Pathologic analyses revealed differences between carbonic anhydrase IX (P = .03) for sites of low StO versus high StO. CD105 displayed a similar trend but was not significant (P = .09). Conclusion Ferumoxytol-based quantitative blood oxygenation level-dependent MRI can potentially be used as a noninvasive surrogate for oxygenation mapping in infiltrative astrocytomas. This technique can potentially be integrated in treatment planning for aggressive targeting of hypoxic areas in tumors.
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http://dx.doi.org/10.1148/radiol.2018172601DOI Listing
September 2018

Incidence and Time of Onset of Osseous Pseudoprogression in Patients With Metastatic Spine Disease From Renal Cell or Prostate Carcinoma After Treatment With Stereotactic Body Radiation Therapy.

Neurosurgery 2019 03;84(3):647-654

Department of Radiation Oncology, University of Toronto, Toronto, Canada.

Background: Tumor osseous pseudoprogression (PP), defined as an imaging-based transient increase in tumor size following treatment, was recently described in patients with spinal metastases following stereotactic body radiation therapy. Distinguishing PP from true tumor progression is critical.

Objective: To describe the incidence, time of onset, and time range of PP following stereotactic body radiation therapy in patients treated for spinal metastases from either prostate cancer (PC) or renal cell carcinoma (RCC), and associated predictive factors.

Methods: A retrospective study was conducted on our institution's cancer database from 2009 to 2015. Selection was based on single level, no prior radiation or surgery, ≥2 follow-up spine magnetic resonance imaging (MRI), and metastases arising from either PC or RCC. Gross tumor volume was contoured on pre- and up to 5 posttreatment MRIs. Patients were sorted into groups depending on gross tumor volume response: PP, non-PP, or progressive disease. Clinical and dosimetric variables were compared using either Fisher's exact test or Kruskal-Wallis analyses.

Results: Forty-three spinal segments from 31 patients were analyzed. RCC and PC patients showed similar incidence of PP (∼37%). Whether the primary was lytic or sclerotic was a significant predictive factor with more PP in the lytic group (P = .0208). There was a trend of earlier PP onset in RCC (within 6-18 mo) as compared to PC; however, PC segments showed more time-confined presentation of PP (9-12 mo).

Conclusion: There was a higher incidence of PP in lytic compared to sclerotic primary tumor type. PP in spinal metastatic sites may have variable presentations depending on the primary cancer.
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http://dx.doi.org/10.1093/neuros/nyy075DOI Listing
March 2019

The effect of white matter hyperintensities on verbal memory: Mediation by temporal lobe atrophy.

Neurology 2018 02 26;90(8):e673-e682. Epub 2018 Jan 26.

From Sunnybrook Research Institute (W.S., M.M., J.R., N.H., J.D.E., M.S., P.C., D.Y., S.M.N., C.J.M.S., M.F.H., A.K., P.I.O., F.G., B.S., J.K., S.S., R.H.S., K.L.L., D.T.S., S.E.B.), Toronto; University of Toronto (W.S., M.M., N.H., M.S., P.C., D.Y., S.M.N., A.K., P.I.O., S.C.S., F.G., B.S., J.K., S.S., R.H.S., K.L.L., D.T.S., S.E.B.); University Health Network Toronto Rehabilitation Institute (W.S., P.I.O., K.L.L.), Canada; Universidade Federal de São Paulo (H.C.-M.), Brazil; McMaster University (D.J.S., S.C.S.), Hamilton; and Rotman Research Institute (D.T.S.), Baycrest, Toronto, Canada.

Objective: To determine the relationship between white matter hyperintensities (WMH) presumed to indicate disease of the cerebral small vessels, temporal lobe atrophy, and verbal memory deficits in Alzheimer disease (AD) and other dementias.

Methods: We recruited groups of participants with and without AD, including strata with extensive WMH and minimal WMH, into a cross-sectional proof-of-principle study (n = 118). A consecutive case series from a memory clinic was used as an independent validation sample (n = 702; Sunnybrook Dementia Study; NCT01800214). We assessed WMH volume and left temporal lobe atrophy (measured as the brain parenchymal fraction) using structural MRI and verbal memory using the California Verbal Learning Test. Using path modeling with an inferential bootstrapping procedure, we tested an indirect effect of WMH on verbal recall that depends sequentially on temporal lobe atrophy and verbal learning.

Results: In both samples, WMH predicted poorer verbal recall, specifically due to temporal lobe atrophy and poorer verbal learning (proof-of-principle -1.53, 95% bootstrap confidence interval [CI] -2.45 to -0.88; and confirmation -0.66, 95% CI [-0.95 to -0.41] words). This pathway was significant in subgroups with (-0.20, 95% CI [-0.38 to -0.07] words, n = 363) and without (-0.71, 95% CI [-1.12 to -0.37] words, n = 339) AD. Via the identical pathway, WMH contributed to deficits in recognition memory (-1.82%, 95% CI [-2.64% to -1.11%]), a sensitive and specific sign of AD.

Conclusions: Across dementia syndromes, WMH contribute indirectly to verbal memory deficits considered pathognomonic of Alzheimer disease, specifically by contributing to temporal lobe atrophy.
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http://dx.doi.org/10.1212/WNL.0000000000004983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818160PMC
February 2018

Differentiating radiation necrosis from tumor progression in brain metastases treated with stereotactic radiotherapy: utility of intravoxel incoherent motion perfusion MRI and correlation with histopathology.

J Neurooncol 2017 Sep 3;134(2):433-441. Epub 2017 Jul 3.

Departments of Radiation Oncology, Odette Cancer Center, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, T2-187, Toronto, ON, M4N3M5, Canada.

Radiation necrosis is a serious potential adverse event of stereotactic radiosurgery that cannot be reliably differentiated from recurrent tumor using conventional imaging techniques. Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) based method that uses a diffusion-weighted sequence to estimate quantitative perfusion and diffusion parameters. This study evaluated the IVIM-derived apparent diffusion coefficient (ADC) and perfusion fraction (f), and compared the results to the gold standard histopathological-defined outcomes of radiation necrosis or recurrent tumor. Nine patients with ten lesions were included in this study; all lesions exhibited radiographic progression after stereotactic radiosurgery for brain metastases that subsequently underwent surgical resection due to uncertainty regarding the presence of radiation necrosis versus recurrent tumor. Pre-surgical IVIM was performed to obtain f and ADC values and the results were compared to histopathology. Five lesions exhibited pathological radiation necrosis and five had predominantly recurrent tumor. The IVIM perfusion fraction reliably differentiated tumor recurrence from radiation necrosis (f = 10.1 ± 0.7 vs. 8.3 ± 1.2, p = 0.02; cutoff value of 9.0 yielding a sensitivity/specificity of 100%/80%) while the ADC did not distinguish between the two (ADC = 1.1 ± 0.2 vs. 1.2 ± 0.4, p = 0.6). IVIM shows promise in differentiating recurrent tumor from radiation necrosis for brain metastases treated with radiosurgery, but needs to be validated in a larger cohort.
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http://dx.doi.org/10.1007/s11060-017-2545-2DOI Listing
September 2017

Motor Phenotype in Neurodegenerative Disorders: Gait and Balance Platform Study Design Protocol for the Ontario Neurodegenerative Research Initiative (ONDRI).

J Alzheimers Dis 2017 ;59(2):707-721

Canadian Partnership for Stroke Recovery Sunnybrook Site, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.

Background: The association of cognitive and motor impairments in Alzheimer's disease and other neurodegenerative diseases is thought to be related to damage in the common brain networks shared by cognitive and cortical motor control processes. These common brain networks play a pivotal role in selecting movements and postural synergies that meet an individual's needs. Pathology in this "highest level" of motor control produces abnormalities of gait and posture referred to as highest-level gait disorders. Impairments in cognition and mobility, including falls, are present in almost all neurodegenerative diseases, suggesting common mechanisms that still need to be unraveled.

Objective: To identify motor-cognitive profiles across neurodegenerative diseases in a large cohort of patients.

Methods: Cohort study that includes up to 500 participants, followed every year for three years, across five neurodegenerative disease groups: Alzheimer's disease/mild cognitive impairment, frontotemporal degeneration, vascular cognitive impairment, amyotrophic lateral sclerosis, and Parkinson's disease. Gait and balance will be assessed using accelerometers and electronic walkways, evaluated at different levels of cognitive and sensory complexity, using the dual-task paradigm.

Results: Comparison of cognitive and motor performances across neurodegenerative groups will allow the identification of motor-cognitive phenotypes through the standardized evaluation of gait and balance characteristics.

Conclusions: As part of the Ontario Neurodegenerative Research Initiative (ONDRI), the gait and balance platform aims to identify motor-cognitive profiles across neurodegenerative diseases. Gait assessment, particularly while dual-tasking, will help dissect the cognitive and motor contribution in mobility and cognitive decline, progression to dementia syndromes, and future adverse outcomes including falls and mortality.
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http://dx.doi.org/10.3233/JAD-170149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523841PMC
April 2018

Temporal evolution of perfusion parameters in brain metastases treated with stereotactic radiosurgery: comparison of intravoxel incoherent motion and dynamic contrast enhanced MRI.

J Neurooncol 2017 Oct 1;135(1):119-127. Epub 2017 Jul 1.

Department of Medical Imaging, Sunnybrook Health Sciences Centre and University of Toronto, 2075 Bayview Ave., Toronto, ON, M4N 3M5, Canada.

Intravoxel incoherent motion (IVIM) is a magnetic resonance imaging (MRI) technique that is seeing increasing use in neuro-oncology and offers an alternative to contrast-enhanced perfusion techniques for evaluation of tumor blood volume after stereotactic radiosurgery (SRS). To date, IVIM has not been validated against contrast enhanced techniques for brain metastases after SRS. In the present study, we measure blood volume for 20 brain metastases (15 patients) at baseline, 1 week and 1 month after SRS using IVIM and dynamic contrast enhanced (DCE)-MRI. Correlation between blood volume measurements made with IVIM and DCE-MRI show poor correlation at baseline, 1 week, and 1 month post SRS (r = 0.33, 0.14 and 0.30 respectively). At 1 week after treatment, no significant change in tumor blood volume was found using IVIM or DCE-MRI (p = 0.81 and 0.41 respectively). At 1 month, DCE-MRI showed a significant decrease in blood volume (p = 0.0002). IVIM, on the other hand, demonstrated the opposite effect and showed a significant increase in blood volume at 1 month (p = 0.03). The results of this study indicate that blood volume measured with IVIM and DCE-MRI are not equivalent. While this may relate to differences in the type of perfusion information each technique is providing, it could also reflect a limitation of tumor blood volume measurements made with IVIM after SRS. IVIM measurements of tumor blood volume in the month after SRS should therefore be interpreted with caution.
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http://dx.doi.org/10.1007/s11060-017-2556-zDOI Listing
October 2017

Radiologic Differences between Human Papillomavirus-Related and Human Papillomavirus-Unrelated Oropharyngeal Carcinoma on Diffusion-Weighted Imaging.

ORL J Otorhinolaryngol Relat Spec 2016 1;78(6):344-352. Epub 2017 Mar 1.

Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Background And Purpose: Human papilloma virus-related oropharyngeal carcinoma (HPV+ OPC) is a unique entity compared to HPV-unrelated (HPV-) OPC. Previous studies were inconclusive regarding the differences between HPV+ and HPV- OPCs on diffusion-weighted imaging (DWI). This study sought to determine if there is an association between HPV status and apparent diffusion coefficient (ADC) values as an imaging biomarker in OPCs.

Materials And Methods: OPC patients with pretreatment MRI including DWI were retrospectively reviewed and analyzed as a blinded, controlled cohort. HPV status was biopsy-ascertained with p16 staining. ADC values were determined by placing the largest possible circular region of interest in solid portions of primary tumors and/or metastatic lymph nodes. Necrotic and cystic portions were excluded.

Results: Twenty-eight HPV+ and 12 HPV- patients were included. Adjusted for age and sex, ADC values were significantly lower in HPV+ OPC primary tumors (p = 0.013) and lymph node metastases (p = 0.013). The area under the curve (AUC) was 0.85 and 0.90, respectively. A model with a linear combination of the 2 variables yielded an AUC of 0.92.

Conclusion: ADC values were significantly lower in both the primary tumors and lymph node metastases in HPV+ OPCs compared to HPV- OPCs. These results confirm the results of prior studies.
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http://dx.doi.org/10.1159/000458446DOI Listing
January 2018

The Ontario Neurodegenerative Disease Research Initiative (ONDRI).

Can J Neurol Sci 2017 Mar 22;44(2):196-202. Epub 2016 Dec 22.

2Robarts Research Institute,Western University,London,Canada.

Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
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http://dx.doi.org/10.1017/cjn.2016.415DOI Listing
March 2017

Magnetic Resonance Imaging Exposure During Pregnancy.

JAMA 2016 Dec;316(21):2275

Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jama.2016.17296DOI Listing
December 2016

Depth of Cochlear Implant Array Within the Cochlea and Performance Outcome.

Ann Otol Rhinol Laryngol 2016 Nov 21;125(11):886-892. Epub 2016 Jul 21.

Department of Otolaryngology and Head and Neck Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto. ON, Canada.

Objective: To evaluate whether the depth of cochlear implant array within the cochlea affects performance outcomes 1 year following cochlear implantation.

Methods: A retrospective case review of 120 patients who were implanted with the Advanced Bionics HiFocus 1J. Post-implantation plain-radiographs were retrospectively reviewed, and the depth of insertion was measured in degrees from the round window to the electrode tip. Correlation between the depth of insertion and 1-year post-activation Hearing in Noise Test (HINT) scores was analyzed. Intrascala position was not assessed.

Results: Depth of electrode insertion ranged from 180° to 720°, and HINT scores ranged from 0% to 100%. A Mann-Whitney U test demonstrated significantly improved 1-year post-activation HINT scores in patients with an insertion depth of 360° or more in comparison with patients with insertion depth of less than 360° (81% vs 61%, P = .048). Patients with 13 to 15 contacts within cochlear turns performed as well as patients with full insertion of all 16 contacts, while patients with only 12 contacts performed poorly.

Conclusions: Insertion depth of the AB HiFocus 1J electrode of less than 360° is associated with reduced 1-year post-activation HINT scores when compared with deeper insertions. Partial insertion of 13 active contacts or more led to similar results as full insertion.
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http://dx.doi.org/10.1177/0003489416660111DOI Listing
November 2016

Diffusion Tensor Imaging Tractography of the Facial Nerve in Patients With Cerebellopontine Angle Tumors.

Otol Neurotol 2016 Apr;37(4):388-93

*Department of Otolaryngology Head and Neck Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada †Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Tel Aviv University, Tel Aviv, Israel ‡Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Objective: To demonstrate the utility of diffusion tensor imaging (DTI) fiber tractography of the facial nerve in patients with cerebellopontine angle (CPA) tumors.

Study Design: Prospective.

Setting: Tertiary referral center.

Patients: DTI technique was established in 113 patients without tumors and in 28 patients with CPA tumors. Subsequently, DTI results were compared with intraoperative findings in 21 patients with medium and large-sized tumors, treated surgically via a translabyrinthine approach.

Intervention: Three Tesla magnetic resonance (MR) was used for DTI tractography. For patients without CPA tumors, the scanning protocol was 32 directions with a 3 × 3 × 3 mm voxel size. For CPA tumor patients, scanning protocol was 32 directions with a 2 × 2 × 2 mm voxel size. DTI data were used to track the facial nerve.

Main Outcome Measures: Facial nerve identification rate.

Results: Facial nerve identification rate in MR-DTI was 97% and 100% in patients without tumors and in patients with tumors of the CPA of the internal auditory canal that were not treated surgically, respectively. MR-DTI identification of the facial nerve was successful in 20 patients who were treated surgically (95%). Good agreement between surgical findings and MR-DTI results was found in 19 patients (90%).

Conclusion: MR DTI tractography is an effective technique in positively identifying the position of the facial nerve in patients with CPA tumors.
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http://dx.doi.org/10.1097/MAO.0000000000000984DOI Listing
April 2016