Publications by authors named "David J Gladstone"

157 Publications

Predictors of neurologists confirming or overturning emergency physicians' diagnosis of TIA or stroke.

CJEM 2021 Sep 1. Epub 2021 Sep 1.

Clinical Epidemiology Unit, F647, The Ottawa Hospital, Ottawa Hospital Research Institute, 1053 Carling Avenue, Ottawa, ON, K1Y 4E9, Canada.

Background: Transient ischemic attack (TIA) and non-disabling stroke are common emergency department (ED) presentations. Currently, there are no prospective multicenter studies determining predictors of neurologists confirming a diagnosis of cerebral ischemia in patients discharged with a diagnosis of TIA or stroke. The objectives were to (1) calculate the concordance between emergency physicians and neurologists for the outcome of diagnosing TIA or stroke, and (2) identify characteristics associated with neurologists diagnosing a stroke mimic.

Methods: This was a planned sub-study of a prospective cohort study at 14 Canadian EDs enrolling patients diagnosed with TIA or non-disabling stroke from 2006 to 2017. Logistic regression was used to identify factors associated with neurologists' diagnosis of cerebral ischemia. Our primary outcome was the composite outcome of cerebral ischemia (TIA or non-disabling stroke) based on the neurologists' assessment.

Results: The diagnosis of cerebral ischemia was confirmed by neurologists in 5794 patients (55.4%). The most common identified stroke mimics were migraine (18%), peripheral vertigo (7%), syncope (4%), and seizure (3%). Over a third of patients (38.4%) ultimately had an undetermined aetiology for their symptoms. The strongest predictors of cerebral ischemia confirmation were infarct on CT (OR 1.83, 95% CI 1.65-2.02), advanced age (OR comparing 75th-25th percentiles 1.67, 1.55-1.80), language disturbance (OR 1.92, 1.75-2.10), and smoking (OR 1.67, 1.46-1.91). The strongest predictors of stroke mimics were syncope (OR 0.59, 0.48-0.72), vertigo (OR 0.52, 0.45-0.59), bilateral symptoms (OR 0.60, 0.50-0.72), and confusion (OR 0.50, 0.44-0.57).

Conclusion: Physicians should have a high index of suspicion of cerebral ischemia in patients with advanced age, smoking history, language disturbance, or infarcts on CT. Physicians should discriminate in which patients to pursue stroke investigations on when deemed at minimal risk of cerebral ischemia, including those with isolated vertigo, syncope, or bilateral symptoms.
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http://dx.doi.org/10.1007/s43678-021-00181-0DOI Listing
September 2021

Optical emission-based phantom to verify coincidence of radiotherapy and imaging isocenters on an MR-linac.

J Appl Clin Med Phys 2021 Sep 19;22(9):252-261. Epub 2021 Aug 19.

Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.

Purpose: Demonstrate a novel phantom design using a remote camera imaging method capable of concurrently measuring the position of the x-ray isocenter and the magnetic resonance imaging (MRI) isocenter on an MR-linac.

Methods: A conical frustum with distinct geometric features was machined out of plastic. The phantom was submerged in a small water tank, and aligned using room lasers on a MRIdian MR-linac (ViewRay Inc., Cleveland, OH). The phantom physical isocenter was visualized in the MR images and related to the DICOM coordinate isocenter. To view the x-ray isocenter, an intensified CMOS camera system (DoseOptics LLC., Hanover, NH) was placed at the foot of the treatment couch, and centered such that the optical axis of the camera was coincident with the central axis of the treatment bore. Two or four 8.3mm x 24.1cm beams irradiated the phantom from cardinal directions, producing an optical ring on the conical surface of the phantom. The diameter of the ring, measured at the peak intensity, was compared to the known diameter at the position of irradiation to determine the Z-direction offset of the beam. A star-shot method was employed on the front face of the frustum to determine X-Y alignment of the MV beam. Known shifts were applied to the phantom to establish the sensitivity of the method.

Results: Couch translations, demonstrative of possible isocenter misalignments, on the order of 1mm were detectable for both the radiotherapy and MRI isocenters. Data acquired on the MR-linac demonstrated an average error of 0.28mm(N=10, R =0.997, σ=0.37mm) in established Z displacement, and 0.10mm(N=5, σ=0.34mm) in XY directions of the radiotherapy isocenter.

Conclusions: The phantom was capable of measuring both the MRI and radiotherapy treatment isocenters. This method has the potential to be of use in MR-linac commissioning, and could be streamlined to be valuable in daily constancy checks of isocenter coincidence.
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http://dx.doi.org/10.1002/acm2.13377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425893PMC
September 2021

Spatial and temporal dosimetry of individual electron FLASH beam pulses using radioluminescence imaging.

Phys Med Biol 2021 Jun 30;66(13). Epub 2021 Jun 30.

Thayer School of Engineering, Dartmouth College, Hanover NH 03755, United States of America.

In this study, spatio-temporal beam profiling for electron ultra-high dose rate (UHDR; >40 Gy s) radiation via Cherenkov emission and radioluminescence imaging was investigated using intensified complementary metal-oxide-semiconductor cameras.The cameras, gated to FLASH optimized linear accelerator pulses, imaged radioluminescence and Cherenkov emission incited by single pulses of a UHDR (>40 Gy s) 10 MeV electron beam delivered to the isocenter. Surface dosimetry was investigated via imaging Cherenkov emission or scintillation from a solid water phantom or GdOS:Tb screen positioned on top of the phantom, respectively. Projected depth-dose profiles were imaged from a tank filled with water (Cherenkov emission) and a 1 g lquinine sulfate solution (scintillation). These optical results were compared with projected lateral dose profiles measured by Gafchromic film at different depths, including the surface.The per-pulse beam output from Cherenkov imaging agreed with the photomultiplier tube Cherenkov output to within 3% after about the first five to seven ramp-up pulses. Cherenkov emission and scintillation were linear with dose ( = 0.987 and 0.995, respectively) and independent of dose rate from ∼50 to 300 Gy s(0.18-0.91 Gy/pulse). The surface dose distribution from film agreed better with scintillation than with Cherenkov emission imaging (3%/3 mm gamma pass rates of 98.9% and 88.8%, respectively). Using a 450 nm bandpass filter, the quinine sulfate-based water imaging of the projected depth optical profiles agreed with the projected film dose to within 5%.The agreement of surface dosimetry using scintillation screen imaging and Gafchromic film suggests it can verify the consistency of daily beam quality assurance parameters with an accuracy of around 2% or 2 mm. Cherenkov-based surface dosimetry was affected by the target's optical properties, prompting additional calibration. In projected depth-dose profiling, scintillation imaging via spectral suppression of Cherenkov emission provided the best match to film. Both camera-based imaging modalities resolved dose from single UHDR beam pulses of up to 60 Hz repetition rate and 1 mm spatial resolution.
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http://dx.doi.org/10.1088/1361-6560/ac0390DOI Listing
June 2021

Deferral of Consent: Recent Lessons From Canadian Acute Stroke Trials.

Stroke 2021 Jul 5;52(7):e326-e327. Epub 2021 May 5.

Ottawa Hospital and Department of Medicine, University of Ottawa (M.S., D.D.), Ontario, Canada.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.121.034655DOI Listing
July 2021

Verification of field match lines in whole breast radiation therapy using Cherenkov imaging.

Radiother Oncol 2021 07 1;160:90-96. Epub 2021 May 1.

Norris Cotton Cancer Center at Dartmouth Hitchcock Medical Center, Lebanon, United States; Geisel School of Medicine, Dartmouth College, Hanover, United States. Electronic address:

Purpose: In mono-isocentric radiation therapy treatment plans designed to treat the whole breast and supraclavicular lymph nodes, the fields meet at isocenter, forming the match line. Insufficient coverage at the match line can lead to recurrence, and overlap over weeks of treatment can lead to increased risk of healthy tissue toxicity. Cherenkov imaging was used to assess the accuracy of delivery at the match line and identify potential incidents during patient treatments.

Methods And Materials: A controlled calibration was constructed from the deconvolved Cherenkov images from the delivery of a modified patient treatment plan to an anthropomorphic phantom with introduced separation and overlap. The trend from this calibration was then used to evaluate the field match line for accuracy and inter-fraction consistency for two patients.

Results: The intersection point between matching field profiles was directly correlated to the distance (gap/overlap) between the fields (anthropomorphic phantom R = 0.994 "breath hold" and R = 0.990 "free breathing"). The profile intersection points from two patients' imaging sessions yielded an average of +1.40 mm offset (overlap) and -1.32 mm offset (gap), thereby introducing roughly a 25.0% over-dose and a -23.6% under-dose (R = 0.994).

Conclusions: This study shows that field match regions can be detected and quantified by taking deconvolved Cherenkov images and using their product image to create steep intensity gradients, causing match lines to stand out. These regions can then be quantitatively translated into a dose consequence. This approach offers a high sensitivity detection method which can quantify match line variability and errors in vivo.
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http://dx.doi.org/10.1016/j.radonc.2021.04.013DOI Listing
July 2021

Visual Isocenter Position Enhanced Review (VIPER): a Cherenkov imaging-based solution for MR-linac daily QA.

Med Phys 2021 Jun 9;48(6):2750-2759. Epub 2021 May 9.

Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.

Purpose: This study demonstrates a robust Cherenkov imaging-based solution to MR-Linac daily QA, including mechanical-imaging-radiation isocenter coincidence verification.

Methods: A fully enclosed acrylic cylindrical phantom was designed to be mountable to the existing jig, indexable to the treatment couch. An ABS plastic conical structure was fixed inside the phantom, held in place with 3D-printed spacers, and filled with water allowing for high edge contrast on MR imaging scans. Both a star shot plan and a four-angle sheet beam plan were delivered to the phantom; the former allowed for radiation isocenter localization in the x-z plane (A/P and L/R directions) relative to physical landmarks on the phantom, and the latter allowed for the longitudinal position of the sheet beam to be encoded as a ring of Cherenkov radiation emitted from the phantom, allowing for isocenter localization on the y-axis (S/I directions). A custom software application was developed to perform near-real-time analysis of the data by any clinical user.

Results: Calibration procedures show that linearity between longitudinal position and optical ring diameter is high (R  > 0.99), and that RMSE is low (0.184 mm). The star shot analysis showed a minimum circle radius of 0.34 mm. The final isocenter coincidence measurements in the lateral, longitudinal, and vertical directions were -0.61 mm, 0.55 mm, and -0.14 mm, respectively, and the total 3D distance coincidence was 0.83 mm, with each of these being below 2 mm tolerance.

Conclusion: This novel system provided an efficient, MR safe, all-in-one method for acquisition and near-real-time analysis of isocenter coincidence data. This represents a direct measurement of the 3D isocentricity. The combination of this phantom and the custom analysis application makes this solution readily clinically deployable after the longitudinal analysis of performance consistency.
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http://dx.doi.org/10.1002/mp.14892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273102PMC
June 2021

Quantification of Oxygen Depletion During FLASH Irradiation In Vitro and In Vivo.

Int J Radiat Oncol Biol Phys 2021 09 18;111(1):240-248. Epub 2021 May 18.

Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Department of Surgery, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire. Electronic address:

Purpose: Delivery of radiation at ultrahigh dose rates (UHDRs), known as FLASH, has recently been shown to preferentially spare normal tissues from radiation damage compared with tumor tissues. However, the underlying mechanism of this phenomenon remains unknown, with one of the most widely considered hypotheses being that the effect is related to substantial oxygen depletion upon FLASH, thereby altering the radiochemical damage during irradiation, leading to different radiation responses of normal and tumor cells. Testing of this hypothesis would be advanced by direct measurement of tissue oxygen in vivo during and after FLASH irradiation.

Methods And Materials: Oxygen measurements were performed in vitro and in vivo using the phosphorescence quenching method and a water-soluble molecular probe Oxyphor 2P. The changes in oxygen per unit dose (G-values) were quantified in response to irradiation by 10 MeV electron beam at either UHDR reaching 300 Gy/s or conventional radiation therapy dose rates of 0.1 Gy/s.

Results: In vitro experiments with 5% bovine serum albumin solutions at 23°C resulted in G-values for oxygen consumption of 0.19 to 0.21 mm Hg/Gy (0.34-0.37 μM/Gy) for conventional irradiation and 0.16 to 0.17 mm Hg/Gy (0.28-0.30 μM/Gy) for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3 ± 0.3 mm Hg in normal tissue and 1.0 ± 0.2 mm Hg in tumor tissue (P < .00001), whereas no decrease in oxygen was observed from a single fraction of 20 Gy applied in conventional mode.

Conclusions: Our observations suggest that oxygen depletion to radiologically relevant levels of hypoxia is unlikely to occur in bulk tissue under FLASH irradiation. For the same dose, FLASH irradiation induces less oxygen consumption than conventional irradiation in vitro, which may be related to the FLASH sparing effect. However, the difference in oxygen depletion between FLASH and conventional irradiation could not be quantified in vivo because measurements of oxygen depletion under conventional irradiation are hampered by resupply of oxygen from the blood.
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http://dx.doi.org/10.1016/j.ijrobp.2021.03.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338745PMC
September 2021

In Reply to Newell et al.

Int J Radiat Oncol Biol Phys 2021 07 31;110(3):909-910. Epub 2021 Mar 31.

Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

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http://dx.doi.org/10.1016/j.ijrobp.2021.03.045DOI Listing
July 2021

A roadmap for research in medical physics via academic medical centers: The DIVERT Model.

Med Phys 2021 Jun 7;48(6):3151-3159. Epub 2021 Apr 7.

Thayer School of Engineering at Dartmouth, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.

The field of medical physics has struggled with the role of research in recent years, as professional interests have dominated its growth toward clinical service. This article focuses on the subset of medical physics programs within academic medical centers and how a refocused academic mission within these centers should drive and support Discovery and Invention with Ventures and Engineering for Research Translation (DIVERT). A roadmap to a DIVERT-based scholarly research program is discussed here around the core building blocks of: (a) creativity in research and team building, (b) improved quality metrics to assess activity, (c) strategic partnerships and spinoff directions that extend capabilities, and (d) future directions driven by faculty-led initiatives. Within academia, it is the unique discoveries and inventions of faculty that lead to their recognition as scholars, and leads to financial support for their research programs and reconition of their intellectual contributions. Innovation must also be coupled to translation to demonstrate outcome successes. These ingredients are critical for research funding, and the two-decade growth in biomedical engineering research funding is an illustration of this, where technology invention has been the goal. This record can be contrasted with flat funding within radiation oncology and radiology, where a growing fraction of research is more procedure-based. However, some centers are leading the change of the definition of medical physics, by the inclusion or assimilation of researchers in fields such as biomedical engineering, machine learning, or data science, thereby widening the scope for new discoveries and inventions. New approaches to the assessment of research quality can help realize this model, revisiting the measures of success and impact. While research partnerships with large industry are productive, newer efforts that foster enterprise startups are changing how institutions see the benefits of the connection between academic innovation and affiliated startup company formation. This innovation-to-enterprise focus can help to cultivate a broader bandwidth of donor-to-investor networks. There are many predictions on future directions in medical physics, yet the actual inventive and discovery steps come from individual research faculty creativity. All success through a DIVERT model requires that faculty-led initiatives span the gap from invention to translation, with support from institutional leadership at all steps in the process. Institutional investment in faculty through endowments or clinical revenues will likely need to increase in the coming years due to the relative decreasing size of grants. Yet, radiology and radiation oncology are both high-revenue, translational fields, with the capacity to synergistically support clinical and research operations through large infrastructures that are mutually beneficial. These roadmap principles can provide a pathway for committed academic medical physics programs in scholarly leadership that will preserve medical physics as an active part of university academics.
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http://dx.doi.org/10.1002/mp.14849DOI Listing
June 2021

Technical Note: Single-pulse beam characterization for FLASH-RT using optical imaging in a water tank.

Med Phys 2021 May 31;48(5):2673-2681. Epub 2021 Mar 31.

Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.

Purpose: High dose rate conditions, coupled with problems related to small field dosimetry, make dose characterization for FLASH-RT challenging. Most conventional dosimeters show significant dependence on dose rate at ultra-high dose rate conditions or fail to provide sufficiently fast temporal data for pulse to pulse dosimetry. Here fast 2D imaging of radioluminescence from a water and quinine phantom was tested for dosimetry of individual 4 μs linac pulses.

Methods: A modified clinical linac delivered an electron FLASH beam of >50 Gy/s to clinical isocenter. This modification removed the x-ray target and flattening filter, leading to a beam that was symmetric and gaussian, as verified with GafChromic EBT-XD film. Lateral projected 2D dose distributions for each linac pulse were imaged in a quinine-doped water tank using a gated intensified camera, and an inverse Abel transform reconstruction provided 3D images for on-axis depth dose values. A total of 20 pulses were delivered with a 10 MeV, 1.5 cm circular beam, and beam with jaws wide open (40 × 40 cm ), and a 3D dose distribution was recovered for each pulse. Beam output was analyzed on a pulse by pulse basis.

Results: The R , D , and the R measured with film and optical methods agreed to within 1 mm for the 1.5 cm circular beam and the beam with jaws wide open. Cross beam profiles for both beams agreed with film data with >95% passing rate (2%/2 mm gamma criteria). The optical central axis depth dose agreed with film data, except for near the surface. A temporal pulse analysis revealed a ramp-up period where the dose per pulse increased for the first few pulses and then stabilized.

Conclusions: Optical imaging of radioluminescence was presented as a valuable tool for establishing a baseline for the recently initiated electron FLASH beam at our institution.
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http://dx.doi.org/10.1002/mp.14843DOI Listing
May 2021

Screening for Atrial Fibrillation in the Older Population: A Randomized Clinical Trial.

JAMA Cardiol 2021 May;6(5):558-567

Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Importance: Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention.

Objective: To evaluate 2 home-based AF screening interventions.

Design, Setting, And Participants: This multicenter randomized clinical trial recruited individuals from primary care practices aged 75 years or older with hypertension and without known AF. From April 5, 2015, to March 26, 2019, 856 participants were enrolled from 48 practices.

Interventions: The control group received standard care (routine clinical follow-up plus a pulse check and heart auscultation at baseline and 6 months). The screening group received a 2-week continuous electrocardiographic (cECG) patch monitor to wear at baseline and at 3 months, in addition to standard care. The screening group also received automated home blood pressure (BP) machines with oscillometric AF screening capability to use twice-daily during the cECG monitoring periods.

Main Outcomes And Measures: With intention-to-screen analysis, the primary outcome was AF detected by cECG monitoring or clinically within 6 months. Secondary outcomes included anticoagulant use, device adherence, and AF detection by BP monitors.

Results: Of the 856 participants, 487 were women (56.9%); mean (SD) age was 80.0 (4.0) years. Median cECG wear time was 27.4 of 28 days (interquartile range [IQR], 18.4-28.0 days). In the primary analysis, AF was detected in 23 of 434 participants (5.3%) in the screening group vs 2 of 422 (0.5%) in the control group (relative risk, 11.2; 95% CI, 2.7-47.1; P = .001; absolute difference, 4.8%; 95% CI, 2.6%-7.0%; P < .001; number needed to screen, 21). Of those with cECG-detected AF, median total time spent in AF was 6.3 hours (IQR, 4.2-14.0 hours; range 1.3 hours-28 days), and median duration of the longest AF episode was 5.7 hours (IQR, 2.9-12.9 hours). Anticoagulation was initiated in 15 of 20 patients (75.0%) with cECG-detected AF. By 6 months, anticoagulant therapy had been prescribed for 18 of 434 participants (4.1%) in the screening group vs 4 of 422 (0.9%) in the control group (relative risk, 4.4; 95% CI, 1.5-12.8; P = .007; absolute difference, 3.2%; 95% CI, 1.1%-5.3%; P = .003). Twice-daily AF screening using the home BP monitor had a sensitivity of 35.0% (95% CI, 15.4%-59.2%), specificity of 81.0% (95% CI, 76.7%-84.8%), positive predictive value of 8.9% (95% CI, 4.9%-15.5%), and negative predictive value of 95.9% (95% CI, 94.5%-97.0%). Adverse skin reactions requiring premature discontinuation of cECG monitoring occurred in 5 of 434 participants (1.2%).

Conclusions And Relevance: In this randomized clinical trial, among older community-dwelling individuals with hypertension, AF screening with a wearable cECG monitor was well tolerated, increased AF detection 10-fold, and prompted initiation of anticoagulant therapy in most cases. Compared with continuous ECG, intermittent oscillometric screening with a BP monitor was an inferior strategy for detecting paroxysmal AF. Large trials with hard clinical outcomes are now needed to evaluate the potential benefits and harms of AF screening.

Trial Registration: ClinicalTrials.gov Identifier: NCT02392754.
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http://dx.doi.org/10.1001/jamacardio.2021.0038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905702PMC
May 2021

Prospective validation of Canadian TIA Score and comparison with ABCD2 and ABCD2i for subsequent stroke risk after transient ischaemic attack: multicentre prospective cohort study.

BMJ 2021 02 4;372:n49. Epub 2021 Feb 4.

Department of Emergency Medicine, Queen's University, Kingston, ON, Canada.

Objective: To validate the previously derived Canadian TIA Score to stratify subsequent stroke risk in a new cohort of emergency department patients with transient ischaemic attack.

Design: Prospective cohort study.

Setting: 13 Canadian emergency departments over five years.

Participants: 7607 consecutively enrolled adult patients attending the emergency department with transient ischaemic attack or minor stroke.

Main Outcome Measures: The primary outcome was subsequent stroke or carotid endarterectomy/carotid artery stenting within seven days. The secondary outcome was subsequent stroke within seven days (with or without carotid endarterectomy/carotid artery stenting). Telephone follow-up used the validated Questionnaire for Verifying Stroke Free Status at seven and 90 days. All outcomes were adjudicated by panels of three stroke experts, blinded to the index emergency department visit.

Results: Of the 7607 patients, 108 (1.4%) had a subsequent stroke within seven days, 83 (1.1%) had carotid endarterectomy/carotid artery stenting within seven days, and nine had both. The Canadian TIA Score stratified the risk of stroke, carotid endarterectomy/carotid artery stenting, or both within seven days as low (risk ≤0.5%; interval likelihood ratio 0.20, 95% confidence interval 0.09 to 0.44), medium (risk 2.3%; interval likelihood ratio 0.94, 0.85 to 1.04), and high (risk 5.9% interval likelihood ratio 2.56, 2.02 to 3.25) more accurately (area under the curve 0.70, 95% confidence interval 0.66 to 0.73) than did the ABCD2 (0.60, 0.55 to 0.64) or ABCD2i (0.64, 0.59 to 0.68). Results were similar for subsequent stroke regardless of carotid endarterectomy/carotid artery stenting within seven days.

Conclusion: The Canadian TIA Score stratifies patients' seven day risk for stroke, with or without carotid endarterectomy/carotid artery stenting, and is now ready for clinical use. Incorporating this validated risk estimate into management plans should improve early decision making at the index emergency visit regarding benefits of hospital admission, timing of investigations, and prioritisation of specialist referral.
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http://dx.doi.org/10.1136/bmj.n49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859838PMC
February 2021

Electron FLASH Delivery at Treatment Room Isocenter for Efficient Reversible Conversion of a Clinical LINAC.

Int J Radiat Oncol Biol Phys 2021 07 11;110(3):872-882. Epub 2021 Jan 11.

Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire; Department of Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

Purpose: In this study, procedures were developed to achieve efficient reversible conversion of a clinical linear accelerator (LINAC) and deliver ultrahigh-dose-rate (UHDR) electron or conventional beams to the treatment room isocenter for FLASH radiation therapy.

Methods And Materials: The LINAC was converted to deliver UHDR beam within 20 minutes by retracting the x-ray target from the beam's path, positioning the carousel on an empty port, and selecting 10 MV photon beam energy in the treatment console. Dose rate surface and depth dose profiles were measured in solid water phantom at different field sizes with Gafchromic film and an optically stimulated luminescent dosimeter (OSLD). A pulse controller counted the pulses via scattered radiation signal and gated the delivery for a preset pulse count. A fast photomultiplier tube-based Cherenkov detector measured the per pulse beam output at a 2-ns sampling rate. After conversion back to clinical mode, conventional beam output, flatness, symmetry, field size, and energy were measured for all clinically commissioned energies.

Results: The surface average dose rates at the isocenter for 1-cm diameter and 1.5-in diameter circular fields and for a jaws-wide-open field were 238 ± 5 Gy/s, 262 ± 5 Gy/s, and 290 ± 5 Gy/s, respectively. The radial symmetry of the beams was within 2.4%, 0.5%, and 0.2%, respectively. The doses from simultaneous irradiation of film and OSLD were within 1%. The photomultiplier tube showed the LINAC required ramp up time in the first 4 to 6 pulses before the output stabilized, after which its stability was within 3%.

Conclusions: At the isocenter of the treatment room, 10 MeV UHDR beams were achieved. The beam output was reproducible but requires further investigation of the ramp up time, equivalent to ∼1 Gy, requiring dose monitoring. The UHDR beam can irradiate both small and large subjects to investigate potential FLASH radiobiological effects in minimally modified clinical settings, and the dose rate can be further increased by reducing the source-to-surface distance.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.011DOI Listing
July 2021

NRG Oncology Survey on Practice and Technology Use in SRT and SBRT Delivery.

Front Oncol 2020 27;10:602607. Epub 2020 Nov 27.

Cancer Institute, Allegheny Health Network, Pittsburgh, PA, United States.

Purpose: To assess stereotactic radiotherapy (SRT)/stereotactic body radiotherapy (SBRT) practices by polling clinics participating in multi-institutional clinical trials.

Methods: The NRG Oncology Medical Physics Subcommittee distributed a survey consisting of 23 questions, which covered general technologies, policies, and procedures used in the Radiation Oncology field for the delivery of SRT/SBRT (9 questions), and site-specific questions for brain SRT, lung SBRT, and prostate SBRT (14 questions). Surveys were distributed to 1,996 radiotherapy institutions included on the membership rosters of the five National Clinical Trials Network (NCTN) groups. Patient setup, motion management, target localization, prescriptions, and treatment delivery technique data were reported back by 568 institutions (28%).

Results: 97.5% of respondents treat lung SBRT patients, 77.0% perform brain SRT, and 29.1% deliver prostate SBRT. 48.8% of clinics require a physicist present for every fraction of SBRT, 18.5% require a physicist present for the initial SBRT fraction only, and 14.9% require a physicist present for the entire first fraction, including set-up approval for all subsequent fractions. 55.3% require physician approval for all fractions, and 86.7% do not reposition without x-ray imaging. For brain SRT, most institutions (83.9%) use a planning target volume (PTV) margin of 2 mm or less. Lung SBRT PTV margins of 3 mm or more are used in 80.6% of clinics. Volumetric modulated arc therapy (VMAT) is the dominant delivery method in 62.8% of SRT treatments, 70.9% of lung SBRT, and 68.3% of prostate SBRT.

Conclusion: This report characterizes SRT/SBRT practices in radiotherapy clinics participating in clinical trials. Data made available here allows the radiotherapy community to compare their practice with that of other clinics, determine what is achievable, and assess areas for improvement.
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http://dx.doi.org/10.3389/fonc.2020.602607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729187PMC
November 2020

Initial Clinical Experience of Cherenkov Imaging in External Beam Radiation Therapy Identifies Opportunities to Improve Treatment Delivery.

Int J Radiat Oncol Biol Phys 2021 04 20;109(5):1627-1637. Epub 2020 Nov 20.

Thayer School of Engineering at Dartmouth, Hanover, New Hampshire.

Purpose: The value of Cherenkov imaging as an on-patient, real-time, treatment delivery verification system was examined in a 64-patient cohort during routine radiation treatments in a single-center study.

Methods And Materials: Cherenkov cameras were mounted in treatment rooms and used to image patients during their standard radiation therapy regimen for various sites, predominantly for whole breast and total skin electron therapy. For most patients, multiple fractions were imaged, with some involving bolus or scintillators on the skin. Measures of repeatability were calculated with a mean distance to conformity (MDC) for breast irradiation images.

Results: In breast treatments, Cherenkov images identified fractions when treatment delivery resulted in dose on the contralateral breast, the arm, or the chin and found nonideal bolus positioning. In sarcoma treatments, safe positioning of the contralateral leg was monitored. For all 199 imaged breast treatment fields, the interfraction MDC was within 7 mm compared with the first day of treatment (with only 7.5% of treatments exceeding 3 mm), and all but 1 fell within 7 mm relative to the treatment plan. The value of imaging dose through clear bolus or quantifying surface dose with scintillator dots was examined. Cherenkov imaging also was able to assess field match lines in cerebral-spinal and breast irradiation with nodes. Treatment imaging of other anatomic sites confirmed the value of surface dose imaging more broadly.

Conclusions: Daily radiation therapy can be imaged routinely via Cherenkov emissions. Both the real-time images and the posttreatment, cumulative images provide surrogate maps of surface dose delivery that can be used for incident discovery and/or continuous improvement in many delivery techniques. In this initial 64-patient cohort, we discovered 6 minor incidents using Cherenkov imaging; these otherwise would have gone undetected. In addition, imaging provides automated, quantitative metrics useful for determining the quality of radiation therapy delivery.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.013DOI Listing
April 2021

The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation.

Can J Cardiol 2020 12 22;36(12):1847-1948. Epub 2020 Oct 22.

Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Québec, Canada.

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.
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http://dx.doi.org/10.1016/j.cjca.2020.09.001DOI Listing
December 2020

Detective quantum efficiency of intensified CMOS cameras for Cherenkov imaging in radiotherapy.

Phys Med Biol 2020 11 12;65(22):225013. Epub 2020 Nov 12.

Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, United States of America.

In this study the metric of detective quantum efficiency (DQE) was applied to Cherenkov imaging systems for the first time, and results were compared for different detector hardware, gain levels and with imaging processing for noise suppression. Intensified complementary metal oxide semiconductor cameras using different image intensifier designs (Gen3 and Gen2+) were used to image Cherenkov emission from a tissue phantom in order to measure the modulation transfer function (MTF) and noise power spectrum (NPS) of the systems. These parameters were used to calculate the DQE for varying acquisition settings and image processing steps. MTF curves indicated that the Gen3 system had superior contrast transfer and spatial resolution than the Gen2+ system, with [Formula: see text] values of 0.52 mm and 0.31 mm, respectively. With median filtering for noise suppression, these values decreased to 0.50 mm and 0.26 mm. The maximum NPS values for the Gen3 and Gen2+ systems at high gain were 1.3 × 10 mm and 9.1 × 10 mm respectively, representing a 14x decrease in noise power for the Gen2+ system. Both systems exhibited increased NPS intensity with increasing gain, while median filtering lowered the NPS. The DQE of each system increased with increasing gain, and at the maximum gain levels the Gen3 system had a low-frequency DQE of 0.31%, while the Gen2+ system had a value of 1.44%. However, at a higher frequency of 0.4 mm, these values became 0.54% and 0.03%. Filtering improved DQE for the Gen3 system and reduced DQE for the Gen2+ system and had a mix of detrimental and beneficial qualitative effects by decreasing the spatial resolution and sharpness but also substantially lowering noise. This methodology for DQE measurement allowed for quantitative comparison between Cherenkov imaging cameras and improvements to their sensitivity, and yielded the first formal assessment of Cherenkov image formation efficiency.
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http://dx.doi.org/10.1088/1361-6560/abb0c5DOI Listing
November 2020

Producing a Beam Model of the Varian ProBeam Proton Therapy System using TOPAS Monte Carlo Toolkit.

Med Phys 2020 Dec 8;47(12):6500-6508. Epub 2020 Nov 8.

Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.

Purpose: A Geant4-based TOPAS Monte Carlo toolkit was utilized to model a Varian ProBeam proton therapy system, with the aim of providing an independent computational platform for validating advanced dosimetric methods.

Materials And Methods: The model was tested for accuracy of dose and linear energy transfer (LET) prediction relative to the commissioning data, which included integral depth dose (IDD) in water and spot profiles in air measured at varying depths (for energies of 70 to 240 MeV in increments of 10 MeV, and 242 MeV), and absolute dose calibration. Emittance was defined based on depth-dependent spot profiles and Courant-Snyder's particle transport theory, which provided spot size and angular divergence along the inline and crossline plane. Energy spectra were defined as Gaussian distributions that best matched the range and maximum dose of the IDD. The validity of the model was assessed based on measurements of range, dose to peak difference, mean point to point difference, spot sizes at different depths, and spread-out Bragg peak (SOBP) IDD and was compared to the current treatment planning software (TPS).

Results: Simulated and commissioned spot sizes agreed within 2.5%. The single spot IDD range, maximum dose, and mean point to point difference of each commissioned energy agreed with the simulated profiles generally within 0.07 mm, 0.4%, and 0.6%, respectively. A simulated SOBP plan agreed with the measured dose within 2% for the plateau region. The protons/MU and absolute dose agreed with the current TPS to within 1.6% and exhibited the greatest discrepancy at higher energies.

Conclusions: The TOPAS model agreed well with the commissioning data and included inline and crossline asymmetry of the beam profiles. The discrepancy between the measured and TOPAS-simulated SOBP plan may be due to beam modeling simplifications of the current TPS and the nuclear halo effect. The model can compute LET, and motivates future studies in understanding equivalent dose prediction in treatment planning, and investigating scintillation quenching.
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http://dx.doi.org/10.1002/mp.14532DOI Listing
December 2020

Recommandations canadiennes pour les pratiques optimales de soins de l’AVC, septième édition : l’acide acétylsalicylique pour la prévention d’événements vasculaires.

CMAJ 2020 Oct;192(40):E1174-E1184

Département de neurologie et neurochirurgie [Wein], Université McGill, Montréal (Qc); Fondation des maladies du cœur et de l'AVC du Canada [Lindsay, Lawrence, Simard, de Jong]; Division de neurologie [Gladstone, Casaubon], Département de médecine, Université de Toronto; Division de neurologie [Gladstone], Service de médecine, Centre régional de traitement des AVC; Programme de sciences neurologiques Hurvitz [Gladstone], Centre des sciences de la santé Sunnybrook; Institut de recherche Sunnybrook [Gladstone], Toronto (Ont.); Centre hospitalier de l'Université de Montréal (CHUM) [Poppe, Gioia], Hôpital Notre-Dame, Montréal (Qc); Département de médecine familiale [Bell, Habert], Université de Toronto; Programme de traitement des AVC de l'hôpital Toronto Western [Casaubon], Réseau universitaire de santé, Toronto (Ont.); workHORSE Consulting Ltd. [Foley], London (Ont.); Département de neurosciences cliniques [Coutts, Smith], École de médecine Cumming, Université de Calgary, Calgary (Alb.); Faculté de médecine (cardiologie) [Cox], Université Dalhousie, Halifax (N.-É.); Département de médecine [Douketis], Université McMaster, Hamilton (Ont.); Division de neurologie [Field], Département de médecine, Université de la Colombie-Britannique, Vancouver (C.-B.); Département de médecine d'urgence [Lang], École de médecine Cumming, Université de Calgary, Calgary Alb.); Division de cardiologie [Mehta], Département de médecine, Université McMaster, Hamilton (Ont.); Département de médecine familiale et communautaire [Papoushek], Faculté de pharmacie Leslie-Dan, Université de Toronto, Toronto (Ont.); École de pharmacie [Semchuk], Université de la Saskatchewan, Saskatoon (Sask.); Division de neurologie [Sharma], Département de médecine, Université McMaster, Hamilton (Ont.); Division cardiovasculaire [Udell], Service de médecine, Hôpital Women's College; Centre de cardiologie Peter-Munk [Udell], Hôpital général de Toronto, Université de Toronto, Toronto (Ont.); Divisions de physiatrie et réadaptation [Mountain] et de neurologie [Gubitz], Département de médecine, Université Dalhousie; Division de neurologie [Dowlatshahi], Faculté de médecine, Université d'Ottawa, Ottawa (Ont.).

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http://dx.doi.org/10.1503/cmaj.191599-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546742PMC
October 2020

Reduction in Stroke After Transient Ischemic Attack in a Province-Wide Cohort Between 2003 and 2015.

Can J Neurol Sci 2021 05 22;48(3):335-343. Epub 2020 Sep 22.

Sunnybrook Research Institute and Sunnybrook Health Sciences Centre, Department of Medicine (Division of Neurology).

Background: Improvements in management of transient ischemic attack (TIA) have decreased stroke and mortality post-TIA. Studies examining trends over time on a provincial level are limited. We analyzed whether efforts to improve management have decreased the rate of stroke and mortality after TIA from 2003 to 2015 across an entire province.

Methods: Using administrative data from the Canadian Institute for Health Information's (CIHI) databases from 2003 to 2015, we identified a cohort of patients with a diagnosis of TIA upon discharge from the emergency department (ED). We examined stroke rates at Day 1, 2, 7, 30, 90, 180, and 365 post-TIA and 1-year mortality rates and compared trends over time between 2003 and 2015.

Results: From 2003 to 2015 in Ontario, there were 61,710 patients with an ED diagnosis of TIA. Linear regressions of stroke after the index TIA showed a significant decline between 2003 and 2015, decreasing by 25% at Day 180 and 32% at 1 year (p < 0.01). The 1-year stroke rate decreased from 6.0% in 2003 to 3.4% in 2015. Early (within 48 h) stroke after TIA continued to represent approximately half of the 1-year event rates. The 1-year mortality rate after ED discharge following a TIA decreased from 1.3% in 2003 to 0.3% in 2015 (p < 0.001).

Interpretation: At a province-wide level, 1-year rates of stroke and mortality after TIA have declined significantly between 2003 and 2015, suggesting that efforts to improve management may have contributed toward the decline in long-term risk of stroke and mortality. Continued efforts are needed to further reduce the immediate risk of stroke following a TIA.
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http://dx.doi.org/10.1017/cjn.2020.205DOI Listing
May 2021

Scintillation imaging as a high-resolution, remote, versatile 2D detection system for MR-linac quality assurance.

Med Phys 2020 Sep 18;47(9):3861-3869. Epub 2020 Jul 18.

Thayer School of Engineering and Geisel School of Medicine, Dartmouth College, Hanover, NH, 03755, USA.

Purpose: To demonstrate the potential benefits of remote camera-based scintillation imaging for routine quality assurance (QA) measurements for magnetic resonance guided radiotherapy (MRgRT) linear accelerators.

Methods: A wall-mounted CMOS camera with a time-synchronized intensifier was used to image photons produced from a scintillation screen in response to dose deposition from a 6 MV FFF x-ray beam produced by a 0.35 T MR-linac. The oblique angle of the field of view was corrected using a projective transform from a checkerboard calibration target. Output sensitivity and constancy was measured using the scintillator and benchmarked against an A28 ion chamber. Field cross-plane and in-plane profiles were measured for field sizes ranging from 1.68 × 1.66 cm to 20.02 × 19.92 cm with both scintillation imaging and using an IC profiler. Multileaf collimator (MLC) shifts were introduced to test sensitivity of the scintillation imaging system to small spatial deviations. A picket fence test and star-shot were delivered to both the scintillator and EBT3 film to compare accuracy in measuring MLC positions and isocenter size.

Results: The scintillation imaging system showed comparable sensitivity and linearity to the ion chamber in response to changes in machine output down to 0.5 MU (R  = 0.99). Cross-plane profiles show strong agreement with defined field sizes using full width half maximum (FWHM) measurement of <2 mm for field sizes below 15 cm, but the oblique viewing angle was the limiting factor in accuracy of in-plane profile widths. However, the system provided high-resolution profiles in both directions for constancy measurements. Small shifts in the field position down to 0.5 mm were detectable with <0.1 mm accuracy. Multileaf collimator positions as measured with both scintillation imaging and EBT3 film were measured within ± 1 mm tolerance and both detection systems produced similar isocenter sizes from the star-shot analysis (0.81 and 0.83 mm radii).

Conclusions: Remote scintillation imaging of a two-dimensional screen provided a rapid, versatile, MR-compatible solution to many routine quality assurance procedures including output constancy, profile flatness and symmetry constancy, MLC position verification and isocenter size. This method is high-resolution, does not require post-irradiation readout, and provides simple, instantaneous data acquisition. Full automation of the readout and processing could make this a very simple but effective QA tool, and is adaptable to all medical accelerators.
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http://dx.doi.org/10.1002/mp.14353DOI Listing
September 2020

Computer animation body surface analysis of total skin electron radiation therapy dose homogeneity via Cherenkov imaging.

J Med Imaging (Bellingham) 2020 May 3;7(3):034002. Epub 2020 Jun 3.

Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States.

Quality assurance (QA) of dose homogeneity in total skin electron therapy (TSET) is challenging since each patient is positioned in six standing poses with two beam angles. Our study tested the feasibility of a unique approach for TSET QA through computational display of the cumulative dose, constructed and synthesized by computer animation methods. Dose distributions from Cherenkov emission images were projected onto a scanned 3D body model. Topographically mapped surfaces of the patient were recorded in each of six different delivery positions, while a Cherenkov camera acquired images. Computer animation methods allowed a fitted 3D human body model of the patient to be created with deformation of the limbs and torso to each position. A two-dimensional skin map was extracted from the 3D model of the full surface of the patient. This allowed the dose mapping to be additively accumulated independent of body position, with the total dose summed in a 2D map and reinterpreted on the 3D body display. For the body model, the mean Hausdorff error distance was below 2 cm, setting the spatial accuracy limit. The dose distribution over the patient's 3D model generally matched the Cherenkov/dose images. The dose distribution mapping was estimated to be near 1.5 cm accuracy based upon a phantom study. The body model must most closely match at the edges of the mesh to ensure that high dose gradients are not projected onto the wrong location. Otherwise 2 to 3 cm level errors in positioning in the mesh do not appear to cause larger than 5% dose errors. The cumulative dose images showed regions of overlap laterally and regions of low intensity in the posterior arms. The proposed modeling and animation can be used to visualize and analyze the accumulated dose in TSET via display of the summed dose/Cherenkov images on a single body surface.
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http://dx.doi.org/10.1117/1.JMI.7.3.034002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267842PMC
May 2020

Atrial Cardiopathy in the Absence of Atrial Fibrillation Increases Risk of Ischemic Stroke, Incident Atrial Fibrillation, and Mortality and Improves Stroke Risk Prediction.

J Am Heart Assoc 2020 06 20;9(11):e013227. Epub 2020 May 20.

Institute for Clinical Evaluative Sciences Toronto Ontario Canada.

Background Atrial fibrillation (AF) is a major, often undetected, cardiac cause of stroke. Markers of atrial cardiopathy, including left atrial enlargement (LAE) or excessive atrial ectopy (EAE) increase the risk of AF and have shown associations with stroke. We sought to determine whether these markers improve stroke risk prediction beyond traditional vascular risk factors (eg CHADS-VASc score). Methods and Results Retrospective longitudinal cohort of 32 454 consecutive community-dwelling adults aged ≥65 years referred for outpatient echocardiogram or Holter in Ontario, Canada (2010-2017). Moderate-severe LAE was defined as men >47 mm and women >43 mm, and EAE was defined as >30 APBs per hour. Cause-specific competing risks Cox proportional hazards used to estimate risk of ischemic stroke (primary), incident AF, and death (secondary). C-statistics, incremental discrimination improvement and net reclassification were used to compare CHADS-VASc with LAE and EAE to CHADS-VASc alone. Each 10 mm increase in left atrial diameter increased 2- and 5-year adjusted cause-specific stroke hazard almost 2-fold (LAE: 2-year hazard ratio (HR), 1.72; =0.007; 5-year HR, 1.87; <0.0001), while EAE showed no significant associations with stroke (2-year HR, 1.00; =0.99; 5-year HR, 1.08, =0.70), adjusting for incident AF. Stroke risk estimation improved significantly at 2 (C-statistics=0.68-0.75, 0.008) and 5 years (C-statistics=0.70-0.76, =0.003) with LAE and EAE. Conclusions LAE was independently associated with an increased risk of ischemic stroke in the absence of AF and both LAE and EAE improved stroke risk prediction. These findings have implications for stroke risk stratification, AF screening, and stroke prevention before the onset of AF.
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http://dx.doi.org/10.1161/JAHA.119.013227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428995PMC
June 2020

Characterization of a new scintillation imaging system for proton pencil beam dose rate measurements.

Phys Med Biol 2020 08 21;65(16):165014. Epub 2020 Aug 21.

Thayer School of Engineering, Dartmouth College, Hanover, NH, United States of America.

The goal of this work was to create a technique that could measure all possible spatial and temporal delivery rates used in pencil-beam scanning (PBS) proton therapy. The proposed system used a fast scintillation screen for full-field imaging to resolve temporal and spatial patterns as it was delivered. A fast intensified CMOS camera used continuous mode with 10 ms temporal frame rate and 1 × 1 mm spatial resolution, imaging a scintillation screen during clinical proton PBS delivery. PBS plans with varying dose, dose rate, energy, field size, and spot-spacing were generated, delivered and imaged. The captured images were post processed to provide dose and dose rate values after background subtraction, perspective transformation, uniformity correction for the camera and the scintillation screen, and calibration into dose. The linearity in scintillation response with respect to varying dose rate, dose, and field size was within 2%. The quenching corrected response with varying energy was also within 2%. Large spatio-temporal variations in dose rate were observed, even for plans delivered with similar dose distributions. Dose and dose rate histograms and maximum dose rate maps were generated for quantitative evaluations. With the fastest PBS delivery on a clinical system, dose rates up to 26.0 Gy s were resolved. The scintillation imaging technique was able to quantify proton PBS dose rate profiles with spot weight as low as 2 MU, with spot-spacing of 2.5 mm, having a 1 × 1 mm spatial resolution. These dose rate temporal profiles, spatial maps, and cumulative dose rate histograms provide useful metrics for the potential evaluation and optimization of dose rate in treatment plans.
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http://dx.doi.org/10.1088/1361-6560/ab9452DOI Listing
August 2020

Canadian Stroke Best Practice Recommendations, seventh edition: acetylsalicylic acid for prevention of vascular events.

CMAJ 2020 03;192(12):E302-E311

Department of Neurology and Neurosurgery (Wein), McGill University, Montréal, Que.; the Heart and Stroke Foundation of Canada (Lindsay, Lawrence, Simard, de Jong); Division of Neurology (Gladstone, Casaubon), Department of Medicine, University of Toronto; Division of Neurology (Gladstone), Department of Medicine, Regional Stroke Centre; Hurvitz Brain Sciences Program (Gladstone), Sunnybrook Health Sciences Centre; Sunnybrook Research Institute (Gladstone); Toronto, Ont.; Centre hospitalier de l'Université de Montréal (CHUM) (Poppe, Gioia), Hôpital Notre-Dame, Montréal, Que.; Department of Family Medicine (Bell, Habert), University of Toronto; Toronto Western Hospital Stroke Program (Casaubon), University Health Network, Toronto, Ont.; workHORSE Consulting Ltd. (Foley), London, Ont.; Department of Clinical Neurosciences (Coutts, Smith), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Faculty of Medicine (Cardiology) (Cox), Dalhousie University, Halifax, NS; Department of Medicine (Douketis), McMaster University, Hamilton, Ont.; Division of Neurology (Field), Department of Medicine, University of British Columbia; Vancouver, BC; Department of Emergency Medicine (Lang), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Division of Cardiology (Mehta), Department of Medicine, McMaster University, Hamilton, Ont.; Department of Family and Community Medicine (Papoushek), Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ont.; College of Pharmacy (Semchuk), University of Saskatchewan, Saskatoon, Sask.; Division of Neurology (Sharma), Department of Medicine, McMaster University, Hamilton, Ont.; Cardiovascular Division (Udell), Department of Medicine Women's College Hospital; Peter Munk Cardiac Centre (Udell), Toronto General Hospital, University of Toronto, Toronto, Ont.; Divisions Physical Medicine and Rehabilitation) (Mountain) and Neurology (Gubitz), Department of Medicine, Dalhousie University; Division of Neurology (Dowlatshahi), Faculty of Medicine, University of Ottawa, Ottawa, Ont.

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http://dx.doi.org/10.1503/cmaj.191599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101172PMC
March 2020

Technical Note: A novel dosimeter improves total skin electron therapy surface dosimetry workflow.

J Appl Clin Med Phys 2020 Jun 19;21(6):158-162. Epub 2020 Apr 19.

Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.

Purpose: The novel scintillator-based system described in this study is capable of accurately and remotely measuring surface dose during Total Skin Electron Therapy (TSET); this dosimeter does not require post-exposure processing or annealing and has been shown to be re-usable, resistant to radiation damage, have minimal impact on surface dose, and reduce chances of operator error compared to existing technologies e.g. optically stimulated luminescence detector (OSLD). The purpose of this study was to quantitatively analyze the workflow required to measure surface dose using this new scintillator dosimeter and compare it to that of standard OSLDs.

Methods: Disc-shaped scintillators were attached to a flat-faced phantom and a patient undergoing TSET. Light emission from these plastic discs was captured using a time-gated, intensified, camera during irradiation and converted to dose using an external calibration factor. Time required to complete each step (daily QA, dosimeter preparation, attachment, removal, registration, and readout) of the scintillator and OSLD surface dosimetry workflows was tracked.

Results: In phantoms, scintillators and OSLDs surface doses agreed within 3% for all data points. During patient imaging it was found that surface dose measured by OSLD and scintillator agreed within 5% and 3% for 35/35 and 32/35 dosimetry sites, respectively. The end-to-end time required to measure surface dose during phantom experiments for a single dosimeter was 78 and 202 sec for scintillator and OSL dosimeters, respectively. During patient treatment, surface dose was assessed at 7 different body locations by scintillator and OSL dosimeters in 386 and 754 sec, respectively.

Conclusion: Scintillators have been shown to report dose nearly twice as fast as OSLDs with substantially less manual work and reduced chances of human error. Scintillator dose measurements are automatically saved to an electronic patient file and images contain a permanent record of the dose delivered during treatment.
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http://dx.doi.org/10.1002/acm2.12880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324701PMC
June 2020

Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion.

Can J Neurol Sci 2020 07 6;47(4):479-485. Epub 2020 Mar 6.

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

Background And Purpose: Large prospective observational studies have cast doubt on the common assumption that endovascular thrombectomy (EVT) is superior to intravenous thrombolysis for patients with acute basilar artery occlusion (BAO). The purpose of this study was to retrospectively review our experience for patients with BAO undergoing EVT with modern endovascular devices.

Methods: All consecutive patients undergoing EVT with either a second-generation stent retriever or direct aspiration thrombectomy for BAO at our regional stroke center from January 1, 2013 to March 1, 2019 were included. The primary outcome measure was functional outcome at 1 month using the modified Rankin Scale (mRS) score. Multivariable logistic regression was used to assess the association between patient characteristics and dichotomized mRS.

Results: A total of 43 consecutive patients underwent EVT for BAO. The average age was 67 years with 61% male patients. Overall, 37% (16/43) of patients achieved good functional outcome. Successful reperfusion was achieved in 72% (31/43) of cases. The median (interquartile range) stroke onset to treatment time was 420 (270-639) minutes (7 hours) for all patients. The procedure-related complication rate was 9% (4/43). On multivariate analysis, posterior circulation Alberta stroke program early computed tomography score and Basilar Artery on Computed Tomography Angiography score were associated with improved functional outcome.

Conclusion: EVT appears to be safe and feasible in patients with BAO. Our finding that time to treatment and successful reperfusion were not associated with improved outcome is likely due to including patients with established infarcts. Given the variability of collaterals in the posterior circulation, the paradigm of utilizing a tissue window may assist in patient selection for EVT. Magnetic resonance imaging may be a reasonable option to determine the extent of ischemia in certain situations.
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http://dx.doi.org/10.1017/cjn.2020.51DOI Listing
July 2020

Tracking tumor radiotherapy response in vivo with Cherenkov-excited luminescence ink imaging.

Phys Med Biol 2020 04 28;65(9):095004. Epub 2020 Apr 28.

Thayer School of Engineering at Dartmouth, Hanover, NH 03755, United States of America.

This study demonstrates remote imaging for in vivo detection of radiation-induced tumor microstructural changes by tracking the diffusive spread of injected intratumor UV excited tattoo ink using Cherenkov-excited luminescence imaging (CELI). Micro-liter quantities of luminescent tattoo ink with UV absorption and visible emission were injected at a depth of 2 mm into mouse tumors prior to receiving a high dose treatment of radiation. X-rays from a clinical linear accelerator were used to excite phosphorescent compounds within the tattoo ink through Cherenkov emission. The in vivo phosphorescence was detected using a time-gated intensified CMOS camera immediately after injection, and then again at varying time points after the ink had broken down with the apoptotic tumor cells. Ex vivo tumors were imaged post-mortem using hyperspectral cryo-fluorescence imaging to quantify necrosis and compared to Cherenkov-excited light imaging of diffusive ink spread measured in vivo. Imaging of untreated control mice showed that ink distributions remained constant after four days with less than 3% diffusive spread measured using full width at 20% max. For all mice, in vivo CELI measurements matched within 12% of the values estimated by the high-resolution ex vivo sliced luminescence imaging of the tumors. The tattoo ink spread in treated mice was found to correlate well with the nonperfusion necrotic core volume (R = 0.92) but not well with total tumor volume changes (R = 0.34). In vivo and ex vivo findings indicate that the diffusive spread of the injected tattoo ink can be related to radiation-induced necrosis, independent of total tumor volume change. Tracking the diffusive spread of the ink allows for distinguishing between an increase in tumor size due to new cellular growth and an increase in tumor size due to edema. Furthermore, the imaging resolution of CELI allows for in vivo tracking of subtle microenvironmental changes which occur earlier than tumor shrinkage and this offers the potential for novel, minimally invasive radiotherapy response assay without interrupting a singular clinical workflow.
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http://dx.doi.org/10.1088/1361-6560/ab7d16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190437PMC
April 2020

Tissue pO distributions in xenograft tumors dynamically imaged by Cherenkov-excited phosphorescence during fractionated radiation therapy.

Nat Commun 2020 Jan 29;11(1):573. Epub 2020 Jan 29.

Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.

Hypoxia in solid tumors is thought to be an important factor in resistance to therapy, but the extreme microscopic heterogeneity of the partial pressures of oxygen (pO) between the capillaries makes it difficult to characterize the scope of this phenomenon without invasive sampling of oxygen distributions throughout the tissue. Here we develop a non-invasive method to track spatial oxygen distributions in tumors during fractionated radiotherapy, using oxygen-dependent quenching of phosphorescence, oxygen probe Oxyphor PtG4 and the radiotherapy-induced Cherenkov light to excite and image the phosphorescence lifetimes within the tissue. Mice bearing MDA-MB-231 breast cancer and FaDu head neck cancer xenografts show different pO responses during each of the 5 fractions (5 Gy per fraction), delivered from a clinical linear accelerator. This study demonstrates subsurface in vivo mapping of tumor pO distributions with submillimeter spatial resolution, thus providing a methodology to track response of tumors to fractionated radiotherapy.
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http://dx.doi.org/10.1038/s41467-020-14415-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989492PMC
January 2020
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