Publications by authors named "Anish Kapadia"

21 Publications

  • Page 1 of 1

Canadian Association of Radiologists Recommendations for the Safe Use of MRI During Pregnancy.

Can Assoc Radiol J 2021 May 17:8465371211015657. Epub 2021 May 17.

Department of Radiology, 12365University of Ottawa, Ottawa, Ontario, Canada.

The use of magnetic resonance imaging (MRI) during pregnancy is associated with concerns among patients and health professionals with regards to fetal safety. In this work, the Canadian Association of Radiologists (CAR) Working Group on MRI in Pregnancy presents recommendations for the use of MRI in pregnancy, derived from literature review as well as expert panel opinions and discussions. The working group, which consists of academic subspecialty radiologists and obstetrician-gynaecologists, aimed to provide updated, evidence-based recommendations addressing safety domains related to energy deposition, acoustic noise, and gadolinium-based contrast agent use based on magnetic field strength (1.5T and 3T) and trimester scanned, in addition to the effects of sedative use and occupational exposure.
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http://dx.doi.org/10.1177/08465371211015657DOI Listing
May 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

Venous dysfunction plays a critical role in "normal" white matter disease of aging.

Med Hypotheses 2021 Jan 24;146:110457. Epub 2020 Dec 24.

Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada. Electronic address:

A ubiquitous finding on MRI in older individuals, age-related cerebral white matter hyperintensities (WMHs) are associated with cognitive decline, dementia, disability, and death. Currently, these findings are thought to represent small infarcts secondary to lipohyalinotic arteriosclerosis. Commonly though, the anatomic distribution of WMHs is often non-arterial, and parallel the deep venous system. Furthermore, there is discrepant evidence for the role of conventional vascular risk factors such as hypertension, carotid atherosclerosis and diabetes for the development and progression of these. Interventions targeting conventional vascular risk factors lack consistency in preventing the progression of WMHs. There is evidence for age-related hemodynamic cervical venous dysfunction resulting in reduced internal jugular vein venous compliance, venous dilatation, and venous reflux. Similarly, venous collagenosis increases with age. Increased blood-brain barrier (BBB) permeability is also noted with aging. Both hemodynamic venous dysfunction, venous sclerosis, and increased BBB permeability are associated with WMHs. We propose that age-related WMHs are a sequalae of venous dysfunction. Venous dysfunction results initially in increased transmission of venous pressures to the brain. Subsequent BBB disruption leads to increased permeability with progression to end-stage findings of age-related WMHs.
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http://dx.doi.org/10.1016/j.mehy.2020.110457DOI Listing
January 2021

Bibliometric evaluation of systematic review and meta analyses published in the top 5 "high-impact" radiology journals.

Clin Imaging 2021 Mar 6;71:52-62. Epub 2020 Nov 6.

Sunnybrook Health Sciences Centre, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Introduction: Meta-analyses provide high-level evidence and understanding their trends may provide understanding of the field as a whole. Bibliometric analysis was undertaken to understand research trends in a particular field or subfield and to assess citation as a measure of impact.

Methods: All journals categorised as "Radiology, Nuclear Medicine & Medical Imaging" under the Web of Science subject category were included. After analyzing impact factors of the journals in up to 2018, the top five journals were identified. The retrieved results were ordered by citation count based on Web of Science and Scopus. Specific parameters regarding the title, journal, publication year, authors, country of origin, institution and university, field of study and funding sources were analyzed.

Results: A total of 139 articles were identified. The mean number of citations per article was 25.3 and 22.6 in Scopus and Web of Science respectively, with four articles receiving 100 or more citations. European Radiology had the greatest number of top cited articles (n = 68; 49%). Most number of articles originated from South Korea (n = 60; 43%) and the commonest field of focus with the most common being oncology (n = 51; 27%).

Conclusion: The top 5 high impact journals published a large number of meta-analysis and systematic reviews. The greatest number of top-cited articles were from South Korea, shifting away from the United States. Large number of studies focused on oncologic imaging, consistent with recent trends towards development of imaging biomarkers and personalized medicine. Author H index did not predict citation number or density.
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http://dx.doi.org/10.1016/j.clinimag.2020.11.008DOI Listing
March 2021

Intersection between sleep and neurovascular coupling as the driving pathophysiology of Alzheimer's disease.

Med Hypotheses 2020 Nov 17;144:110283. Epub 2020 Sep 17.

Department of Medical Imaging, University of Toronto, Canada. Electronic address:

Alzheimer's disease (AD) is the commonest cause of dementia. There are tremendous personal and systemic costs associated with the disease. Although there has been significant progress in understanding the disease process, the precise pathophysiologic mechanism remains elusive. The amyloid hypothesis is the leading theory with impaired clearance of the amyloid beta (Aβ) believed to be the underpinning disease process. However, what triggers and propagates the accumulation of Aβ remains unclear. We propose that the impairment of neurovascular coupling triggers a cascade that ultimately leads to impaired Aβ clearance. With aging there is a generalized decline in cerebral blood flow and impairment of cerebrovascular reactivity. With impairment of this neurovascular coupling, the normal bulk clearance of cerebrospinal fluid and interstitial fluid (ISF) becomes hindered. We postulate that this clearance process occurs during non-rapid eye movement slow wave sleep, driven by the tight neurovascular coupling, via a pump-like action. The impairment of ISF clearance results in change in the interstitial microenvironment from accumulation of metabolites, reactive oxygen species, metal ions and results in decreased pH. The changes in the microenvironment promotes the accumulation and aggregation of Aβ, heralding the disease process.
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http://dx.doi.org/10.1016/j.mehy.2020.110283DOI Listing
November 2020

Pipeline Embolization in Patients with Posterior Circulation Subarachnoid Hemorrhages: Is Takotsubo Cardiomyopathy a Limiting Factor?

World Neurosurg 2020 11 7;143:e523-e528. Epub 2020 Aug 7.

Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah. Electronic address:

Background: Hemorrhagic vascular lesions in the posterior cerebral circulation such as ruptured aneurysms and dissections can be challenging to treat. Flow diversion has become an important off-label option, but few studies have analyzed the safety of these devices in this setting. Using an international, multicenter cohort, we reviewed posterior circulation subarachnoid hemorrhage (SAH) patients treated with the Pipeline Embolization Device (PED) in the acute setting and assessed the incidence of Takotsubo cardiomyopathy (TCM).

Methods: Eleven neurovascular centers were queried to identify cases of posterior circulation aneurysms or dissections treated with the PED in the acute setting of SAH. Among those, 5 centers had cases that matched the inclusion criteria. The following variables were evaluated: demographics, the location and morphology of the aneurysm, the clinical presentation, the specific form of treatment, complications including the development of TCM, antiplatelet medication regimen, and follow-up time.

Results: A total of 23 patients were treated with PED after posterior circulation SAH, and 13% of these developed TCM. The lesions were the result of hemorrhagic intracranial dissection (8 patients), ruptured pseudoaneurysm (3), ruptured saccular aneurysm (7), blister aneurysm (4), and fusiform aneurysm (1). Ninety-one percent of patients had complete or near-complete aneurysm occlusion on follow-up imaging. Five patients died in the perioperative period; 16/18 survivors had a favorable outcome.

Conclusions: We describe an unexpectedly high incidence of TCM after the placement of PEDs in patients with posterior circulation SAH in our large case series. Further studies will be needed to elucidate possible causes.
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http://dx.doi.org/10.1016/j.wneu.2020.08.013DOI Listing
November 2020

Multimodal MRI for MRgFUS in essential tremor: post-treatment radiological markers of clinical outcome.

J Neurol Neurosurg Psychiatry 2020 09 10;91(9):921-927. Epub 2020 Jul 10.

Division of Neurosurgery, University Health Network, Toronto, Ontario, Canada

Background: MRI-guided focused ultrasound (MRgFUS) thalamotomy is a promising non-invasive treatment option for medication-resistant essential tremor. However, it has been associated with variable efficacy and a relatively high incidence of adverse effects.

Objectives: To assess the evolution of radiological findings after MRgFUS thalamotomy and to evaluate their significance for clinical outcomes.

Methods: Ninety-four patients who underwent MRgFUS between 2012 and 2017 were retrospectively evaluated. Lesion characteristics were assessed on routine MRI sequences, as well as with tractography. Relationships between imaging appearance, extent of white matter tract lesioning (59/94, on a 4-point scale) and clinical outcome were investigated. Recurrence was defined as >33% loss of tremor suppression at 3 months relative to day 7.

Results: Acute lesions demonstrated blood products, surrounding oedema and peripheral diffusion restriction. The extent of dentatorubrothalamic tract (DRTT) lesioning was significantly associated with clinical improvement at 1 year (t=4.32, p=0.001). Lesion size decreased over time (180.8±91.5 mm at day 1 vs 19.5±19.3 mm at 1-year post-treatment). Higher post-treatment oedema (t=3.59, p<0.001) was associated with larger lesions at 3 months. Patients with larger lesions at day 1 demonstrated reduced rates of tremor recurrence (t=2.67, p=0.019); however, lesions over 170 mm trended towards greater incidence of adverse effects (sensitivity=0.60, specificity=0.63). Lesion encroachment on the medial lemniscus (Sn=1.00, Sp=0.32) and pyramidal tract (Sn=1.00, Sp=0.12) were also associated with increased adverse effects incidence.

Conclusion: Lesion size at day 1 predicts symptom recurrence, with fewer recurrences seen with larger lesions. Greater DRTT lesioning is associated with treatment efficacy. These findings may have implications for lesion targeting and extent.

Trial Registration Number: NCT02252380.
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http://dx.doi.org/10.1136/jnnp-2020-322745DOI Listing
September 2020

Vertebral artery aneurysms and the risk of cord infarction following spinal artery coverage during flow diversion.

J Neurosurg 2020 Mar 27:1-10. Epub 2020 Mar 27.

10Department of Neurosurgery, Geisinger Health System, Danville, Pennsylvania; and.

Objective: Coverage of the anterior spinal artery (ASA) ostia is a source of considerable consternation regarding flow diversion (FD) in vertebral artery (VA) aneurysms due to cord supply. The authors sought to assess the association between coverage of the ASA, posterior spinal artery (PSA), or lateral spinal artery (LSA) ostia when placing flow diverters in distal VAs and clinical outcomes, with emphasis on cord infarction.

Methods: A multicenter retrospective study of 7 institutions in which VA aneurysms were treated with FD between 2011 and 2019 was performed. The authors evaluated the risk of ASA and PSA/LSA occlusion, associated thromboembolic complication, complications overall, aneurysm occlusion status, and functional outcome.

Results: Sixty patients with 63 VA and posterior inferior cerebellar artery aneurysms treated with FD were identified. The median aneurysm diameter was 7 mm and fusiform type was the commonest morphology (42.9%). During a procedure, 1 (61.7%) or 2 (33.3%) flow diverters were placed. Complete occlusion was achieved in 71.9%. Symptomatic thromboembolic complications occurred in 7.4% of cases and intracranial hemorrhage in 10.0% of cases. The ASA and PSA/LSA were identified in 51 (80.9%) and 35 (55.6%) complications and covered by the flow diverter in 29 (56.9%) and 13 (37.1%) of the procedures, respectively. Patency after flow diverter coverage on last follow-up was 89.2% for ASA and 100% for PSA/LSA, not significantly different between covered and noncovered groups (p = 0.5 and p > 0.99, respectively). No complications arose from coverage.

Conclusions: FD aneurysm treatment in the posterior circulation with coverage of ASA or PSA/LSA was not associated with higher rates of occlusion of these branches or any instances of cord infarction.
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http://dx.doi.org/10.3171/2020.1.JNS193293DOI Listing
March 2020

Multiple sclerosis is a systemic venous vasculopathy: A single unifying mechanism.

Med Hypotheses 2020 Feb 26;140:109645. Epub 2020 Feb 26.

Sunnybrook Health Sciences Centre, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Multiple sclerosis (MS) is a potentially debilitating disease affecting the central nervous system (CNS) clinically characterized by progressive neurological deterioration. It is the most common condition under the umbrella of demyelinating disease, thought to occur as a result of a primary autoimmune insult. Various genetic and environmental risk factors have been implicated as potential triggers and/or predisposing factors; however, the exact mechanism of disease remains elusive. Diagnosis and management are based on clinical presentation, with adjunct imaging and biochemical assessment. Since the 19th century anatomical distribution of lesions in MS have been observed to demonstrate a characteristic periventricular, perivenular distribution; spinal cord and cortical lesions also demonstrate this perivenous preponderance. Venous abnormalities have long been observed on pathology characterized by irregular narrowing and dilatation with associated venous wall and perivenous infiltrates. Active CNS lesions are characterized by perivenular inflammatory infiltrates. There is accompanying global dysfunction of the blood-brain barrier, even within normal appearing tissue, with low levels of inflammatory change and tissue injury seen at pathology. Although several CNS antigens have been identified as potential candidates, including myelin related antigens, a specific pathogenic antigen remains elusive. Evaluation of the cerebrospinal fluid reveals characteristic oligoclonal bands, indicating a broad inflammatory response against a variety of CNS antigens. Antibodies have been identified against endothelial elements in sera of patients with MS, their role is not yet clearly elucidated. Emerging evidence suggests there may be a more systemic inflammatory process, heralded by a systemic preclinical prodrome. In light of such seemingly-discrepant clinical, anatomic, immunologic and pathologic findings we propose a unifying theory; specifically we propose that MS is a primary autoimmune vasculopathy, with a predilection of CNS venous structures. Characteristic CNS lesions are a secondary manifestation resulting from an inflammatory response to the uncovering of usually privileged CNS antigens.
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http://dx.doi.org/10.1016/j.mehy.2020.109645DOI Listing
February 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

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

Spinal intraoperative three-dimensional navigation: correlation between clinical and absolute engineering accuracy.

Spine J 2017 04 21;17(4):489-498. Epub 2016 Oct 21.

Division of Neurosurgery, Department of Surgery, University of Toronto, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Institute of Medical Science, School of Graduate Studies, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Biophotonics and Bioengineering Laboratory, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada; Department of Electrical and Computer Engineering, Ryerson University, 350 Victoria St., Toronto, ON, M5B 2K3, Canada. Electronic address:

Background Context: Spinal intraoperative computer-assisted navigation (CAN) may guide pedicle screw placement. Computer-assisted navigation techniques have been reported to reduce pedicle screw breach rates across all spinal levels. However, definitions of screw breach vary widely across studies, if reported at all. The absolute quantitative error of spinal navigation systems is theoretically a more precise and generalizable metric of navigation accuracy. It has also been computed variably and reported in less than a quarter of clinical studies of CAN-guided pedicle screw accuracy.

Purpose: This study aimed to characterize the correlation between clinical pedicle screw accuracy, based on postoperative imaging, and absolute quantitative navigation accuracy.

Design/setting: This is a retrospective review of a prospectively collected cohort.

Patient Sample: We recruited 30 patients undergoing first-time posterior cervical-thoracic-lumbar-sacral instrumented fusion±decompression, guided by intraoperative three-dimensional CAN.

Outcome Measures: Clinical or radiographic screw accuracy (Heary and 2 mm classifications) and absolute quantitative navigation accuracy (translational and angular error in axial and sagittal planes).

Methods: We reviewed a prospectively collected series of 209 pedicle screws placed with CAN guidance. Each screw was graded clinically by multiple independent raters using the Heary and 2 mm classifications. Clinical grades were dichotomized per convention. The absolute accuracy of each screw was quantified by the translational and angular error in each of the axial and sagittal planes.

Results: Acceptable screw accuracy was achieved for significantly fewer screws based on 2 mm grade versus Heary grade (92.6% vs. 95.1%, p=.036), particularly in the lumbar spine. Inter-rater agreement was good for the Heary classification and moderate for the 2 mm grade, significantly greater among radiologists than surgeon raters. Mean absolute translational-angular accuracies were 1.75 mm-3.13° and 1.20 mm-3.64° in the axial and sagittal planes, respectively. There was no correlation between clinical and absolute navigation accuracy.

Conclusions: Radiographic classifications of pedicle screw accuracy vary in sensitivity across spinal levels, as well as in inter-rater reliability. Correlation between clinical screw grade and absolute navigation accuracy is poor, as surgeons appear to compensate for navigation registration error. Future studies of navigation accuracy should report absolute translational and angular errors. Clinical screw grades based on postoperative imaging may be more reliable if performed in multiple by radiologist raters.
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http://dx.doi.org/10.1016/j.spinee.2016.10.020DOI Listing
April 2017

Spinal metastases: multimodality imaging in diagnosis and stereotactic body radiation therapy planning.

Future Oncol 2017 Jan 15;13(1):77-91. Epub 2016 Aug 15.

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

Due to increased effectiveness of cancer treatments and increasing survival rates, metastatic disease has become more frequent compared to the past, with the spine being the most common site of bony metastases. Diagnostic imaging is an integral part of screening, diagnosis and follow-up of spinal metastases. In this article, we review the principles of multimodality imaging for tumor detection with respect to their value for diagnosis and stereotactic body radiation therapy planning for spinal metastases. We will also review the current international consensus agreement for stereotactic body radiation therapy planning, and the role of imaging in achieving the best possible treatment plan.
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http://dx.doi.org/10.2217/fon-2016-0238DOI Listing
January 2017

Molecular Changes Associated with the Protective Effects of Angiopoietin-1 During Blood-Brain Barrier Breakdown Post-Injury.

Mol Neurobiol 2017 08 22;54(6):4232-4242. Epub 2016 Jun 22.

Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada.

Blood-brain barrier (BBB) breakdown to plasma proteins leads to vasogenic edema which when diffuse is a life threatening complication in many types of acute brain injury. In our previous studies, early BBB breakdown was associated with increased expression of endothelial caveolin-1α (Cav-1) protein and decreased expression of occludin. In order to attenuate these changes, the effects of intra-cortical angiopoietin-1 (Ang1), a potent anti-permeability factor, on BBB breakdown was assessed in the cold injury model at day 1 post-injury. Overall vascular permeability at the lesion site was assessed in Ang1 non-treated and treated cold-injured rats, using horseradish peroxidase (HRP) as a tracer and in individual vessels by dual labeling immunofluorescence for Cav-1 or occludin and fibronectin, a marker of BBB breakdown. In addition, Cav-1, occludin, Akt, and ERK1/2 expression at the lesion site was detected by immunoblotting. Non-treated cold-injured rats showed focal HRP leakage at the lesion site which was significantly decreased (P < 0.001) in the Ang1-treated group. Increased endothelial Cav-1 and decreased occludin immunoreactivity was observed in arterioles and corresponding-sized venules with BBB breakdown in the non-treated cold-injured rats, and similar expression of these proteins was detected at the lesion site by immunoblotting associated with increased expression of Akt and ERK2 proteins. These alterations were attenuated by Ang1 treatment which resulted in Cav-1, occludin, Akt, and ERK1/2 protein expression that was similar to that of the control groups as was the endothelial Cav-1 and occludin immunoreactivity in leaky vessels. These data suggest that Ang1 administered early post-injury has potential in attenuating the degree of vascular alterations and subsequent vasogenic edema.
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http://dx.doi.org/10.1007/s12035-016-9973-4DOI Listing
August 2017

Neurosurgical management of a giant colloid cyst with atypical clinical and radiological presentation.

J Neurosurg 2014 Nov 22;121(5):1185-8. Epub 2014 Aug 22.

Departments of Medical Imaging.

The finding of a colloid cyst on neuroimaging is often incidental. These lesions are usually located at the foramen of Monro, are hyperdense on CT scans, and generally demonstrate signal intensity of water on MR images, although this depends on their content. When symptomatic, they frequently present with headaches and nausea due to an obstructive hydrocephalus. The authors describe a case of a giant colloid cyst in a patient presenting with complete left-sided vision loss and progressive memory loss, two very atypical findings in colloid cyst presentation. Imaging findings were also atypical, and this case proved to be a diagnostic dilemma because of its clinical and radiological presentation. Histopathological investigation was of utmost importance in the final diagnosis of a colloid cyst. To the authors' knowledge this colloid cyst is larger than any other described in the literature.
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http://dx.doi.org/10.3171/2014.7.JNS14242DOI Listing
November 2014

Nonaneurysmal perimesencephalic subarachnoid hemorrhage: diagnosis, pathophysiology, clinical characteristics, and long-term outcome.

World Neurosurg 2014 Dec 5;82(6):1131-43. Epub 2014 Jul 5.

Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada; Keenan Research Centre of the Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, ON, Canada. Electronic address:

Patients with nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) have no discernible source for the bleeding and generally are considered to have a benign condition. Correctly diagnosing these patients is essential because a missed aneurysm can have catastrophic consequences. Those presenting with NAPSAH have a low risk of complications and better outcome than patients presenting with aneurysmal subarachnoid hemorrhage; however, a limited body of literature suggests that not all of these patients are able to return to their premorbid functional status. Clinical screens of cognitive status, such as the mini-mental status examination, suggest good recovery of these patients, although these tests may lack sensitivity for identifying deficits in this patient population. More comprehensive neuropsychologic testing in some studies has identified deficits in a wide range of cognitive domains at long-term follow-up in patients with NAPSAH. Because these patients often do not lose consciousness (and thus do not have substantial transient global ischemia) and they do not undergo a procedure for aneurysm repair, the cognitive sequelae can be explained by the presence of blood in the subarachnoid space. NAPSAH presents an opportunity to understand the effects of subarachnoid blood in a clinical setting.
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http://dx.doi.org/10.1016/j.wneu.2014.07.006DOI Listing
December 2014

Effect of aneurysmal subarachnoid hemorrhage on word generation.

Behav Neurol 2014 2;2014:610868. Epub 2014 Mar 2.

Keenan Research Centre for Biomedical Science, the Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, Toronto, ON, Canada M5B 1T8 ; Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A8 ; Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada M5B 1W8 ; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada M5S 3G9.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) survivors commonly exhibit impairment on phonemic and semantic fluency tests; however, it is unclear which of the contributing cognitive processes are compromised in aSAH patients. One method of disentangling these processes is to compare initial word production, which is a rapid, semiautomatic, frontal-executive process, and late phase word production, which is dependent on more effortful retrieval and lexical size and requires a more distributed neural network.

Methods: Seventy-two individuals with aSAH and twenty-five control subjects were tested on a cognitive battery including the phonemic and semantic fluency task. Demographic and clinical information was also collected.

Results: Compared to control subjects, patients with aSAH were treated by clipping and those with multiple aneurysms were impaired across the duration of the phonemic test. Among patients treated by coiling, those with anterior communicating artery aneurysms or a neurological complication (intraventricular hemorrhage, vasospasm, and edema) showed worse output only in the last 45 seconds of the phonemic test. Patients performed comparably to control subjects on the semantic test.

Conclusions: These results support a "diffuse damage" hypothesis of aSAH, indicated by late phase phonemic fluency impairment. Overall, the phonemic and semantic tests represent a viable, rapid clinical screening tool in the postoperative assessment of patients with aSAH.
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http://dx.doi.org/10.1155/2014/610868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006618PMC
December 2014

Impact of global cerebral atrophy on clinical outcome after subarachnoid hemorrhage.

J Neurosurg 2013 Jul 10;119(1):198-206. Epub 2013 May 10.

Division of Neurosurgery, St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.

Object: Atrophy in specific brain areas correlates with poor neuropsychological outcome after subarachnoid hemorrhage (SAH). Few studies have compared global atrophy in SAH with outcome. The authors examined the relationship between global brain atrophy, clinical factors, and outcome after SAH.

Methods: This study was a post hoc exploratory analysis of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1) trial, a randomized, double-blind, placebo-controlled trial of 413 patients with aneurysmal SAH. Patients with infarctions or areas of encephalomalacia on CT, and those with large clip/coil artifacts, were excluded. The 97 remaining patients underwent CT at baseline and 6 weeks, which was analyzed using voxel-based volumetric measurements. The percentage difference in volume between time points was compared against clinical variables. The relationship with clinical outcome was modeled using univariate and multivariate analysis.

Results: Older age, male sex, and systemic inflammatory response syndrome (SIRS) during intensive care stay were significantly associated with brain atrophy. Greater brain atrophy was significantly associated with poor outcome on the modified Rankin scale (mRS), severity of deficits on the National Institutes of Health Stroke Scale (NIHSS), worse executive functioning, and lower EuroQol Group-5D (EQ-5D) score. Adjusted for confounders, brain atrophy was not significantly associated with Mini-Mental State Examination and Functional Status Examination scores. Brain atrophy was not associated with angiographic vasospasm or delayed ischemic neurological deficit.

Conclusions: Worse mRS score, NIHSS score, executive functioning, and EQ-5D scores were associated with greater brain atrophy and older age, male sex, and SIRS burden. These data suggest outcome is associated with factors that cause global brain injury independent of focal brain injury.
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http://dx.doi.org/10.3171/2013.3.JNS121950DOI Listing
July 2013

Detection of multiple proteins in intracerebral vessels by confocal microscopy.

Methods Mol Biol 2011 ;686:177-92

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Assessment of the blood-brain barrier (BBB) may involve the localization of endothelial proteins within the context of endothelial permeability to plasma proteins. The use of antibodies conjugated to fluorescent dyes, coupled with analysis by confocal microscopy, allows for the detection of multiple proteins in components of the neurovascular unit including endothelium and astrocytes. This chapter provides a detailed protocol for detection of three proteins in fixed or frozen sections of rat brain using three fluorophores with unique excitation/emission spectra. Also included is a protocol for tyramide signal amplification, which is useful for detecting proteins of low abundance, and methods for quantitation of intracerebral vessels expressing a particular protein of interest with and without BBB breakdown to plasma proteins.
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http://dx.doi.org/10.1007/978-1-60761-938-3_7DOI Listing
June 2011