Publications by authors named "Chris Heyn"

26 Publications

  • Page 1 of 1

ADC, D, f dataset calculated through the simplified IVIM model, with MGMT promoter methylation, age, and ECOG, in 38 patients with wildtype IDH glioblastoma.

Data Brief 2021 Apr 15;35:106950. Epub 2021 Mar 15.

Department of Radiation Oncology, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.

Patients undergoing standard chemoradiation post-resection had MRIs at radiation planning and fractions 10 and 20 of chemoradiation. MRIs were 1.5T and 3D T2-FLAIR, pre- and post-contrast 3D T1-weighted (T1) and echo planar DWI with three b-values (0, 500, and 1000s/mm) were acquired. T2-FLAIR was coregistered to T1C images. Non-overlapping T1 contrast-enhancing (T1C) and nonenhancing T2-FLAIR hyperintense regions were segmented, with necrotic/cystic regions, the surgical cavity, and large vessels excluded. The simplified IVIM model was used to calculate voxelwise diffusion coefficient () and perfusion fraction () maps; ADC was calculated using the natural logarithm of  = 1000 over  = 0 images. T1C and T2-FLAIR segmentations were brought into this space, and medians calculated. MGMT promoter methylation status (MGMT), age at diagnosis, and Eastern Cooperative Oncology Group (ECOG) performance status were extracted from electronic medical records. The data were presented, analyzed, and described in the article, "Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype Glioblastoma", published in Radiotherapy and Oncology [1].
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http://dx.doi.org/10.1016/j.dib.2021.106950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039816PMC
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

Predicting response to radiotherapy of intracranial metastases with hyperpolarized [Formula: see text]C MRI.

J Neurooncol 2021 May 19;152(3):551-557. Epub 2021 Mar 19.

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

Background: Stereotactic radiosurgery (SRS) is used to manage intracranial metastases in a significant fraction of patients. Local progression after SRS can often only be detected with increased volume of enhancement on serial MRI scans which may lag true progression by weeks or months.

Methods: Patients with intracranial metastases (N = 11) were scanned using hyperpolarized [Formula: see text]C MRI prior to treatment with stereotactic radiosurgery (SRS). The status of each lesion was then recorded at six months post-treatment follow-up (or at the time of death).

Results: The positive predictive value of [Formula: see text]C-lactate signal, measured pre-treatment, for prediction of progression of intracranial metastases at six months post-treatment with SRS was 0.8 [Formula: see text], and the AUC from an ROC analysis was 0.77 [Formula: see text]. The distribution of [Formula: see text]C-lactate z-scores was different for intracranial metastases from different primary cancer types (F = 2.46, [Formula: see text]).

Conclusions: Hyperpolarized [Formula: see text]C imaging has potential as a method for improving outcomes for patients with intracranial metastases, by identifying patients at high risk of treatment failure with SRS and considering other therapeutic options such as surgery.
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http://dx.doi.org/10.1007/s11060-021-03725-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084843PMC
May 2021

Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype glioblastoma.

Radiother Oncol 2021 03 5;156:258-265. Epub 2021 Jan 5.

Department of Radiation Oncology, Sunnybrook Health Sciences Center, University of Toronto, Canada.

Background: Prediction of early progression in glioblastoma may provide an opportunity to personalize treatment. Simplified intravoxel incoherent motion (IVIM) MRI offers quantitative estimates of diffusion and perfusion metrics. We investigated whether these metrics, during chemoradiation, could predict treatment outcome.

Methods: 38 patients with newly diagnosed IDH-wildtype glioblastoma undergoing 6-week/30-fraction chemoradiation had standardized post-operative MRIs at baseline (radiation planning), and at the 10th and 20th fractions. Non-overlapping T1-enhancing (T1C) and non-enhancing T2-FLAIR hyperintense regions were independently segmented. Apparent diffusion coefficient (ADC, ADC) and perfusion fraction (f, f) maps were generated with simplified IVIM modelling. Parameters associated with progression before or after 6.9 months (early vs late progression, respectively), overall survival (OS) and progression-free survival (PFS) were investigated.

Results: Higher ADC at baseline [Odds Ratio (OR) = 1.06, 95% CI 1.01-1.15, p = 0.025], lower f at fraction 10 (OR = 2.11, 95% CI 1.04-4.27, p = 0.018), and lack of increase in ADC at fraction 20 compared to baseline (OR = 1.12, 95% CI 1.02-1.22, p = 0.02) were associated with early progression. Combining ADC at baseline, f at fraction 10, ECOG and MGMT promoter methylation status significantly improved AUC to 90.3% compared to a model with only ECOG and MGMT promoter methylation status (p = 0.001). Using multivariable analysis, neither IVIM metrics were associated with OS but higher f at fraction 10 (HR = 0.72, 95% CI 0.56-0.95, p = 0.018) was associated with longer PFS.

Conclusion: ADC at baseline, its lack of increase from baseline to fraction 20, or f at fraction 10 significantly predicted early progression. f at fraction 10 was associated with PFS.
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http://dx.doi.org/10.1016/j.radonc.2020.12.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186561PMC
March 2021

Use of radiomics for the prediction of local control of brain metastases after stereotactic radiosurgery.

Neuro Oncol 2020 06;22(6):797-805

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

Background: Local response prediction for brain metastases (BM) after stereotactic radiosurgery (SRS) is challenging, particularly for smaller BM, as existing criteria are based solely on unidimensional measurements. This investigation sought to determine whether radiomic features provide additional value to routinely available clinical and dosimetric variables to predict local recurrence following SRS.

Methods: Analyzed were 408 BM in 87 patients treated with SRS. A total of 440 radiomic features were extracted from the tumor core and the peritumoral regions, using the baseline pretreatment volumetric post-contrast T1 (T1c) and volumetric T2 fluid-attenuated inversion recovery (FLAIR) MRI sequences. Local tumor progression was determined based on Response Assessment in Neuro-Oncology‒BM criteria, with a maximum axial diameter growth of >20% on the follow-up T1c indicating local failure. The top radiomic features were determined based on resampled random forest (RF) feature importance. An RF classifier was trained using each set of features and evaluated using the area under the receiver operating characteristic curve (AUC).

Results: The addition of any one of the top 10 radiomic features to the set of clinical features resulted in a statistically significant (P < 0.001) increase in the AUC. An optimized combination of radiomic and clinical features resulted in a 19% higher resampled AUC (mean = 0.793; 95% CI = 0.792-0.795) than clinical features alone (0.669, 0.668-0.671).

Conclusions: The increase in AUC of the RF classifier, after incorporating radiomic features, suggests that quantitative characterization of tumor appearance on pretreatment T1c and FLAIR adds value to known clinical and dosimetric variables for predicting local failure.
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http://dx.doi.org/10.1093/neuonc/noaa007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283017PMC
June 2020

Adverse Radiation Effect After Hypofractionated Stereotactic Radiosurgery in 5 Daily Fractions for Surgical Cavities and Intact Brain Metastases.

Int J Radiat Oncol Biol Phys 2020 03 9;106(4):772-779. Epub 2020 Jan 9.

Department of Radiation Oncology, University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.

Purpose: Limited data exist quantifying the risk of adverse radiation effect (ARE) specific to hypofractionated stereotactic radiosurgery (HSRS). We present our analyses of the risk of ARE after 5 daily fractions of HSRS to surgical cavities and intact metastases.

Methods And Materials: One hundred and eighty-seven consecutively treated patients with 118 surgical cavities and 132 intact metastases were retrospectively reviewed. All patients were treated with 5 daily fractions with a 2 mm planning target volume applied. Clinical and dosimetric variables were assessed to identify predictors of ARE.

Results: The median total prescribed dose was 30 Gy (range, 20-35 Gy) and median follow-up was 12 months. One hundred forty-four patients (77%) received treatment to a single target. Median planning target volumes for resection cavity and intact metastases were 24.9 cm and 7.7 cm, respectively. ARE and symptomatic ARE were observed 21.2% and 10.8% of targets, respectively, and the median time to ARE was 8 months. Time to ARE was <6 months for 38%, 6 to 12 months for 43%, and >12 months for 19% of targets. Multivariable analysis identified intact metastases versus cavities (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.33-10) as a significant predictor of symptomatic ARE. Specific to cavity HSRS, prior whole brain radiation therapy (OR 7.73; 95% CI, 1.67-35.69) and prior stereotactic radiosurgery (OR 8.66; 95% CI, 1.14-65.7) were significant predictors of symptomatic ARE. For intact metastases, the total brain minus gross tumor volume (GTV) receiving 30 Gy (BMC30) was a significant predictor of symptomatic ARE (OR, 1.21; 95% CI, 1.02-1.43), and a volume-based BMC30 threshold of 10.5 cm was significant with an OR of 7.21 (95% CI, 1.31-39.45).

Conclusions: The risk of ARE was greater for intact metastases compared with cavities after HSRS. For intact lesions, the BMC30 was predictive for symptomatic necrosis, and a threshold of 10.5 cm may guide treatment planning.
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http://dx.doi.org/10.1016/j.ijrobp.2019.12.002DOI Listing
March 2020

Lactate topography of the human brain using hyperpolarized C-MRI.

Neuroimage 2020 01 23;204:116202. Epub 2019 Sep 23.

Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Lactate is now recognized as an important intermediate in brain metabolism, but its role is still under investigation. In this work we mapped the distribution of lactate and bicarbonate produced from intravenously injected C-pyruvate over the whole brain using a new imaging method, hyperpolarized C MRI (N = 14, ages 23 to 77). Segmenting the C-lactate images into brain atlas regions revealed a pattern of lactate that was preserved across individuals. Higher lactate signal was observed in cortical grey matter compared to white matter and was highest in the precuneus, cuneus and lingual gyrus. Bicarbonate signal, indicating flux of [1-C]pyruvate into the TCA cycle, also displayed consistent spatial distribution. One-way ANOVA to test for significant differences in lactate among atlas regions gave F = 87.6 and p < 10. This report of a "lactate topography" in the human brain and its consistent pattern is evidence of region-specific lactate biology that is preserved across individuals.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116202DOI Listing
January 2020

Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases.

Neuro Oncol 2020 01;22(1):84-93

Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Background: The objective was to evaluate the risk and predictors of developing leptomeningeal disease (LMD) in patients with brain metastases treated with 5-fraction hypofractionated stereotactic radiotherapy (HSRT).

Methods: Patients treated with HSRT for intact brain metastases and/or surgical cavities were reviewed from a prospectively maintained database. Radiographic patterns of LMD were classified as focal classical, diffuse classical, focal nodular, and diffuse nodular.

Results: HSRT was delivered, most commonly 30 Gy in 5 fractions, to 320 intracranial lesions (57% intact and 43% surgical cavities) in 235 patients. The median follow-up was 13.4 months (range, 0.8 to 60 mo). LMD developed in 19% of patients with a 1-year LMD rate of 12%. From the diagnosis of LMD, the median overall survival (OS) was 3.8 months (range, 2-20.8 mo). The most common LMD pattern was diffuse nodular (44%). No difference in OS was observed between LMD patterns (P = 0.203). Multivariable analysis identified surgical cavities at significantly higher risk of LMD compared with intact lesions (odds ratio [OR] = 2.30, 95% CI: 1.24, 4.29, P = 0.008). For cavities, radiosensitive tumors (OR = 2.35, 95% CI: 1.04, 5.35, P = 0.041) predicted for LMD, while, for intact metastases, patients receiving treatment with targeted agents or immunotherapy (TA/I) were at lower risk (OR = 0.178, 95% CI: 0.04, 0.79, P = 0.023).

Conclusions: Patients who had a brain metastasis resected were at an increased risk of LMD. OS was poor despite treatment of LMD, and no differences in OS based on the pattern of LMD was observed. Treatment with TA/I was observed to be protective against LMD and requires further study.
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http://dx.doi.org/10.1093/neuonc/noz144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954436PMC
January 2020

Image-Guided, Linac-Based, Surgical Cavity-Hypofractionated Stereotactic Radiotherapy in 5 Daily Fractions for Brain Metastases.

Neurosurgery 2019 11;85(5):E860-E869

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.

Background: Cavity stereotactic radiotherapy has emerged as a standard option following resection of brain metastases. However, the optimal approach with either single-fraction or hypofractionated stereotactic radiotherapy (HSRT) remains a significant question.

Objective: To report outcomes for 5-fraction HSRT to the surgical cavity, based on contouring according to a recently reported international consensus guideline.

Methods: Patients treated with cavity HSRT were identified from a prospective institutional database. Local brain control (LC), distant brain failure (DBF), leptomeningeal disease (LMD), and overall survival rates were determined. Univariate and multivariable analyses were performed on potential predictive factors.

Results: One hundred thirty-seven cavities in 122 patients were treated at a median total dose of 30 Gy (range, 25-35 Gy). The median follow-up was 16 mo (range, 1-60 mo). Nonsmall cell lung cancer was the most common histology (44%), followed by breast cancer (21%). In 57% of surgical cavities, the preoperative tumor diameter was >3 cm. One-year LC, DBF, LMD, and overall survival rates were 84%, 45%, 22%, and 62%, respectively. Multivariable analyses identified colorectal (hazard ratio [HR] 4.1, P = .0066) and melanoma (HR 2.4, P = .012) metastases as predictors of local recurrence; preoperative tumor diameter >2 cm (HR 8.9, P = .012) and absence of targeted therapy (HR 4.4, P = .03) as predictors of DBF; and breast cancer histology (HR 2.1, P = .05) and subtotal resection (HR 2.6, P = .009) as predictors of LMD. Symptomatic radiation necrosis was observed in 7 patients (6%).

Conclusion: High rates of LC were observed following this 5-fraction HSRT regimen. Superiority as compared to single-fraction SRS requires a randomized trial.
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http://dx.doi.org/10.1093/neuros/nyz162DOI Listing
November 2019

High Speed, High Density Intraoperative 3D Optical Topographical Imaging with Efficient Registration to MRI and CT for Craniospinal Surgical Navigation.

Sci Rep 2018 10 5;8(1):14894. Epub 2018 Oct 5.

Biophotonics and Bioengineering Laboratory, Ryerson University Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Intraoperative image-guided surgical navigation for craniospinal procedures has significantly improved accuracy by providing an avenue for the surgeon to visualize underlying internal structures corresponding to the exposed surface anatomy. Despite the obvious benefits of surgical navigation, surgeon adoption remains relatively low due to long setup and registration times, steep learning curves, and workflow disruptions. We introduce an experimental navigation system utilizing optical topographical imaging (OTI) to acquire the 3D surface anatomy of the surgical cavity, enabling visualization of internal structures relative to exposed surface anatomy from registered preoperative images. Our OTI approach includes near instantaneous and accurate optical measurement of >250,000 surface points, computed at >52,000 points-per-second for considerably faster patient registration than commercially available benchmark systems without compromising spatial accuracy. Our experience of 171 human craniospinal surgical procedures, demonstrated significant workflow improvement (41 s vs. 258 s and 794 s, p < 0.05) relative to benchmark navigation systems without compromising surgical accuracy. Our advancements provide the cornerstone for widespread adoption of image guidance technologies for faster and safer surgeries without intraoperative CT or MRI scans. This work represents a major workflow improvement for navigated craniospinal procedures with possible extension to other image-guided applications.
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http://dx.doi.org/10.1038/s41598-018-32424-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173775PMC
October 2018

Stereotactic Body Radiotherapy for Spinal Metastases at the Extreme Ends of the Spine: Imaging-Based Outcomes for Cervical and Sacral Metastases.

Neurosurgery 2019 11;85(5):605-612

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Background: The unique anatomy and biomechanical features of the cervical spine and sacrum may impact treatment outcomes following spine stereotactic body radiotherapy (SBRT). Current data for spine metastases are not specific for these locations.

Objective: To report imaging-based SBRT outcomes to cervical and sacral metastases.

Methods: We retrospectively reviewed our prospective spine SBRT database for cervical and sacral metastases. Patients were followed at 2- to 3-mo intervals with a clinical visit and full spine magnetic resonance imaging (MRI) and we report overall survival (OS), vertebral compression fracture (VCF), and MR imaging-based local control (LC) rates.

Results: Fifty-two patients and 93 treated spinal segments were identified. Fifty-six segments were within the cervical spine and 37 within the sacrum, the median follow-up was 14.4 and 19.5 mo, and the median total dose/number of fractions was 24 Gy/2, respectively. Cumulative LC at 1 and 2 yr were 94.5% and 92.7% for the cervical cohort, and 86.5% and 78.7% in the sacral cohort, respectively. Lack of posterior spinal element involvement in the cervical spine (P < .0001) and absence of epidural disease (hazard ratio 0.275, 95% confidence interval 0.076-0.989, P = .048) in the sacral cohort predicted LC. Median OS was 16.3 and 28.5 mo in the cervical spine and sacrum cohorts, respectively. Two cases of sacral VCF, 1 brachial plexopathy, and 1 lumbar-sacral plexopathy were observed.

Conclusion: Although high rates of LC were observed, strategies specific to the sacrum may require further optimization.
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http://dx.doi.org/10.1093/neuros/nyy393DOI Listing
November 2019

Postoperative stereotactic body radiotherapy for spinal metastases.

Chin Clin Oncol 2017 Sep;6(Suppl 2):S18

Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada.

Spine is a common site of metastases in cancer patients. Spine surgery is indicated for select patients, typically those with mechanical instability and/or malignant epidural spinal cord (or cauda equina) compression. Although post-operative conventional palliative external beam radiation therapy has been the standard of care, technical improvements in radiation planning and image-guided radiotherapy have allowed for the application of stereotactic body radiotherapy (SBRT) to the spine. Spine SBRT is intended to ablate residual tumor and optimize local control by delivering several fold greater biologically effective doses. Early clinical experience of postoperative spinal SBRT report encouraging results in terms of safety and efficacy. In this review, we summarize the clinical and technical aspects pertinent to a safe and effective practice of postoperative SBRT for spinal metastases.
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http://dx.doi.org/10.21037/cco.2017.06.27DOI Listing
September 2017

Outcome Evaluation of Acute Ischemic Stroke Patients Treated with Endovascular Thrombectomy: A Single-Institution Experience in the Era of Randomized Controlled Trials.

World Neurosurg 2017 Mar 23;99:593-598. Epub 2016 Dec 23.

Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery, Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Faculty of Applied Sciences and Engineering, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Endovascular thrombectomy is an effective procedure to treat selected ischemic strokes, as shown in recent randomized controlled trials (RCTs). The generalizability of these trial data to real-world settings, however, is unknown. The aim of this study was to examine our single-center experience with endovascular thrombectomy for acute ischemic strokes and perform a comparative outcome analysis to the most recent RCTs.

Methods: We performed a 5-year retrospective analysis, from April 2011 to March 2016, on 66 consecutive patients with acute ischemic stroke who received endovascular thrombectomy at our institution. The Alberta Stroke Program Early CT Score (ASPECTS) and the National Institutes of Health Stroke Scale were used to assess preoperative status. Our primary outcomes were the modified Rankin Score (mRS) at 90 days and recanalization grade measured by the 6-point thrombolysis in cerebral infarction (TICI) grading system.

Results: Sixty-six patients received endovascular treatment during the study period. Among the patients examined, 35 (53%) had a favorable outcome (mRS 0-2 at 90 days), 23 (35%) a poor outcome (mRS 3-5), and 8 (12%) died. Successful recanalization (TICI score 3-5) was achieved in 68% of cases. In univariate analysis, patients with good outcome at 90 days had significantly greater ASPECTS, lower National Institutes of Health Stroke Scale, and higher TICI scores. In a multiple logistic regression model, higher ASPECTS and TICI scores were significantly and independently associated with favorable outcome.

Conclusions: Excellent outcomes, as demonstrated by the recent RCTs, can be achieved in clinical practice and reproduced in dedicated tertiary centers.
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http://dx.doi.org/10.1016/j.wneu.2016.12.054DOI 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

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

Susceptibility-weighted Imaging in Neurovascular Disease.

Top Magn Reson Imaging 2016 Apr;25(2):63-71

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

Susceptibility-weighted imaging (SWI) has become an important imaging sequence in the evaluation of patients with neurovascular disease. In this review, we provide a general overview of the physics of SWI and describe how image contrast is produced with this technique. We provide a general approach and differential diagnosis for 2 commonly encountered radiographic patterns seen with SWI in neurovascular disease. Finally, we discuss specific neurovascular applications of SWI, including its application in acute stroke, vascular malformations, venous thrombosis, and evaluation of cerebral microbleeds.
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http://dx.doi.org/10.1097/RMR.0000000000000079DOI Listing
April 2016

The predictive capacity of apparent diffusion coefficient (ADC) in response assessment of brain metastases following radiation.

Clin Exp Metastasis 2016 Mar 19;33(3):277-84. Epub 2016 Jan 19.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.

To investigate the predictive capacity of the apparent diffusion coefficient (ADC) as a biomarker of radiation response in brain metastases. Seventy brain metastases from 42 patients treated with either stereotactic radiosurgery or whole brain radiotherapy were imaged at baseline, 1 week, and 1 month post-treatment using diffusion-weighted MRI. Mean and median relative ADC for metastases was calculated by normalizing ADC measurements to baseline ADC. At 1 year post-treatment, or last available follow-up MRI, volume criteria determined final tumour response status. Uni- and multivariate analysis was used to account for factors associated with tumour response at 1 week and 1 month. A generalized estimating equations model took into consideration multiple tumours per subject. Optimal thresholds that distinguished responders from non-responders, as well as sensitivity and specificity were determined by receiver operator characteristic analysis and Youden's index. Lower relative ADC values distinguished responders from non-responders at 1 week and 1 month (P < 0.05). Optimal cut-off values for response were 1.060 at 1 week with a sensitivity and specificity of 75.0 and 56.3 %, respectively. At 1 month, the cut-off was 0.971 with a sensitivity and specificity of 70.0 and 68.8 %, respectively. A multivariate general estimating equations analysis identified no prior radiation [odds ratio (OR) 0.211 and 0.137, P = 0.033 and 0.0177], and a lower median relative ADC at 1 week and 1 month (OR 0.619 and 0.694, P = 0.0036 and 0.005), as predictors of tumour response. Lower relative ADC values at 1 week and 1 month following radiation distinguished responders from non-responders and may be a promising biomarker of early radiation response.
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http://dx.doi.org/10.1007/s10585-016-9778-xDOI Listing
March 2016

Advances in pediatric neuroimaging.

Indian J Pediatr 2015 Feb 6;82(2):154-65. Epub 2015 Jan 6.

Division of Pediatric Neuroradiology, Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, ON, Canada,

Conventional MRI protocols are an integral part of routine clinical imaging in pediatric patients. The advent of several newer MRI techniques provides crucial insight into the structural integrity and functional aspects of the developing brain, especially with the introduction of 3T MRI systems in clinical practice. The field of pediatric neuroimaging continues to evolve, with greater emphasis on high spatial resolution, faster scan time, as well as a quest for visualization of the functional aspects of the human brain. MR vendors are increasingly focusing on optimizing MR technology to make it suitable for children, in whom as compared to adults the head size is usually smaller and demonstrates inherent neuroanatomical differences relating to brain development. The eventual goal of these advances would be to evolve as potential biomarkers for predicting neurodevelopment outcomes and prognostication, in addition to their utility in routine diagnostic and therapeutic decision-making. Advanced MR techniques like diffusion tensor imaging, functional MRI, MR perfusion, spectroscopy, volumetric imaging and arterial spin labeling add to our understanding of normal brain development and pathophysiology of various neurological disease processes. This review is primarily focused on outlining advanced MR techniques and their current and potential pediatric neuroimaging applications as well as providing a brief overview of advances in hardware and machine design.
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http://dx.doi.org/10.1007/s12098-014-1657-3DOI Listing
February 2015

Longitudinal quantitative MRI in multiple system atrophy and progressive supranuclear palsy.

Parkinsonism Relat Disord 2014 Feb 12;20(2):222-5. Epub 2013 Oct 12.

Department of Medical Imaging, Toronto Western Hospital, the Joint Department of Medical Imaging, and The University of Toronto, Canada. Electronic address:

Objective: MRI has been used in parkinsonism to assess atrophy, tissue water diffusivity, and mineral deposition but usually at a single time-point. However, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are progressive diseases. This study assessed the value of longitudinal MRI in characterizing the time course of the degenerative process.

Methods: Two serial MRIs (mean 23 months apart) were retrospectively analyzed in 12 MSA, 6 PSP, and 18 age and sex matched controls. Assessment included selected cross-sectional areas, regional apparent diffusion coefficient (ADC) and gradient echo (GRE) intensity ratios of the lateral ventricles, caudate, putamen, middle cerebellar peduncle, pons and midbrain.

Results: On follow-up imaging, there was a larger ADC increase in the putamen in PSP over time compared to controls (p = 0.02). In MSA there was greater volume loss in the pons over time compared to controls (p = 0.002). In MSA the changes in middle cerebellar peduncle ADC were correlated with motor symptom severity according to the Unified Parkinson's Disease Rating Scale Part III (p = 0.005).

Conclusions: Evidence of progressive neurodegeneration can be observed on MRI in MSA and PSP within two years consisting of increasing putaminal ADC in PSP and pontine atrophy in MSA.
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http://dx.doi.org/10.1016/j.parkreldis.2013.10.002DOI Listing
February 2014

MRI of the pancreas: problem solving tool.

J Magn Reson Imaging 2012 Nov;36(5):1037-51

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

Advances in MR hardware and pulse sequence design over the years have improved the quality and robustness of MR imaging of the pancreas. Today, MRI is an indispensible tool for studying the pancreas and can provide useful information not attainable with other noninvasive or minimally invasive imaging techniques. In the present review, specific cases are reviewed where the strengths of MRI demonstrate the utility of this imaging modality as a problem solving tool.
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http://dx.doi.org/10.1002/jmri.23708DOI Listing
November 2012

Ex-vivo cellular MRI with b-SSFP: quantitative benefits of 3T over 1.5 T.

MAGMA 2008 Jul 25;21(4):251-9. Epub 2008 Jun 25.

Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada.

Introduction: The use of MRI with iron-based magnetic nanoparticles for imaging cells is a rapidly growing field of research. We have recently reported that single iron-labeled cells could be detected, as signal voids, in vivo in mouse brains using a balanced steady-state free precession imaging sequence (b-SSFP) and a customized microimaging system at 1.5 T.

Methods: In the current study we assess the benefits, and challenges, of using a higher magnetic field strength for imaging iron-labeled cells with b-SSFP, using ex vivo mouse brain specimens imaged with near identical systems at 1.5 and 3.0 T.

Results: The substantial banding artifact that appears in 3 T b-SSFP images was readily minimized with RF phase cycling, allowing for banding-free b-SSFP images to be compared between the two field strengths. This study revealed that with an optimal 3 T b-SSFP imaging protocol, more than twice as many signal voids were detected as with 1.5 T.

Conclusion: There are several factors that contributed to this important result. First, a greater-than-linear SNR gain was achieved in mouse brain images at 3 T. Second, a reduction in the bandwidth, and the associated increase in repetition time and SNR, produced a dramatic increase in the contrast generated by iron-labeled cells.
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http://dx.doi.org/10.1007/s10334-008-0118-2DOI Listing
July 2008

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Magn Reson Med 2006 Nov;56(5):1001-10

Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.
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http://dx.doi.org/10.1002/mrm.21029DOI Listing
November 2006

In vivo magnetic resonance imaging of single cells in mouse brain with optical validation.

Magn Reson Med 2006 Jan;55(1):23-9

Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.

In the current work we demonstrate, for the first time, that single cells can be detected in mouse brain in vivo using magnetic resonance imaging (MRI). Cells were labeled with superparamagnetic iron oxide nanoparticles and injected into the circulation of mice. Individual cells trapped within the microcirculation of the brain could be visualized with high-resolution MRI using optimized MR hardware and the fast imaging employing steady state acquisition (FIESTA) pulse sequence on a 1.5 T clinical MRI scanner. Single cells appear as discrete signal voids on MR images. Direct optical validation was provided by coregistering signal voids on MRI with single cells visualized using high-resolution confocal microscopy. This work demonstrates the sensitivity of MRI for detecting single cells in small animals for a wide range of application from stem cell to cancer cell tracking.
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http://dx.doi.org/10.1002/mrm.20747DOI Listing
January 2006

Detection threshold of single SPIO-labeled cells with FIESTA.

Magn Reson Med 2005 Feb;53(2):312-20

Imaging Research Laboratories, Robarts Research Institute, London, Canada.

MRI of superparamagnetic iron oxide (SPIO)-labeled cells has become a valuable tool for studying the in vivo trafficking of transplanted cells. Cellular detection with MRI is generally considered to be orders of magnitude less sensitive than other techniques, such as positron emission tomography (PET), single photon emission-computed tomography (SPECT), or optical fluorescence microscopy. However, an analytic description of the detection threshold for single SPIO-labeled cells and the parameters that govern detection has not been adequately provided. In the present work, the detection threshold for single SPIO-labeled cells and the effect of resolution and SNR were studied for a balanced steady-state free precession (SSFP) sequence (3D-FIESTA). Based on the results from both theoretical and experimental analyses, an expression that predicts the minimum detectable mass of SPIO (m(c)) required to detect a single cell against a uniform signal background was derived: m(c) = 5v/(K(fsl) x SNR), where v is the voxel volume, SNR is the image signal-to-noise ratio, and K(fsl) is an empirical constant measured to be 6.2 +/- 0.5 x 10(-5) microl/pgFe. Using this expression, it was shown that the sensitivity of MRI is not very different from that of PET, requiring femtomole quantities of SPIO iron for detection under typical micro-imaging conditions (100 microm isotropic resolution, SNR = 60). The results of this work will aid in the design of cellular imaging experiments by defining the lower limit of SPIO labeling required for single cell detection at any given resolution and SNR.
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http://dx.doi.org/10.1002/mrm.20356DOI Listing
February 2005

Imaging single mammalian cells with a 1.5 T clinical MRI scanner.

Magn Reson Med 2003 May;49(5):968-71

Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada.

In the present work, we demonstrate that the steady-state free precession (SSFP) imaging pulse sequence FIESTA (fast imaging employing steady state acquisition) used in conjunction with a custom-built insertable gradient coil and customized RF coils can be used to detect individual SPIO-labeled cells using a commonly available 1.5 T clinical MRI scanner. This work provides the first evidence that single-cell tracking will be possible using clinical MRI scanners, opening up new possibilities for cell tracking and monitoring of cellular therapeutics in vivo in humans.
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http://dx.doi.org/10.1002/mrm.10417DOI Listing
May 2003