Evaluating the Outcomes and Trainee Performance of a Canadian Medical Imaging Clinician Investigator Program.

Purpose: To measure the research productivity of trainees from the University of Toronto's Medical Imaging Clinician Investigator Program (MI-CIP) and comparing it with the research productivity of trainees from MI-non-CIP and General Surgery (GSx) Clinician Investigator Program. Methods: We identified residents who completed an MI-CIP, MI-non-CIP and GSx-CIP from 2006-2016. In each group of trainees, we assessed 3 research productivity outcomes with non-parametric tests before residency and at 7 years post-CIP completion/post-graduation. Research productivity outcomes include the number of total publications, the number of first-author publications, and the publication's average journal impact factor (IF). Results: We identified 11 MI-CIP trainees (male/female: 9 [82%]/2 [18%]), 74 MI-non-CIP trainees (46 [62%]/28 [38%]) and 41 GSx-CIP trainees (23 [56%]/18 [44%]). MI-CIP trainees had statistically significant higher research productivity than MI-non-CIP in all measured outcomes. The median (interquartile range, IQR) number of total publications of MI-CIP vs MI-non-CIP trainees was 5.0 (8.0) vs 1.0 (2.0) before residency and 6.0 (10.0) vs .0 (2.0) at 7 years post-CIP completion/post-graduation. The median (IQR) first-author publications of MI-CIP vs MI-non-CIP trainees was 2.0 (3.0) vs .0 (1.0) before residency and 2.0 (4.0) vs (.0) (1.0) at 7 years post-CIP completion/post-graduation. The median (IQR) average journal IF of MI-CIP vs MI-non-CIP trainees was 3.2 (2.0) vs .3 (2.4) before residency and 3.9 (3.2) vs .0 (2.6) at 7 years post-CIP completion/post-graduation. Between MI-CIP and GSx-CIP trainees, there were no significant differences in research productivity in all measured outcomes. Conclusion: MI-CIP trainees actively conducted research after graduation. These trainees demonstrated early research engagement before residency. The similar research productivity of MI-CIP vs GSx-CIP trainees shows initial success of MI-CIP trainees.

Multinational Survey of Current Practice from Imaging to Treatment of Atherosclerotic Carotid Stenosis.

BACKGROUND: In the last 20-30 years, there have been many advances in imaging and therapeutic strategies for symptomatic and asymptomatic individuals with carotid artery stenosis. Our aim was to examine contemporary multinational practice standards. METHODS: Departmental Review Board approval for this study was obtained, and 3 authors prepared the 44 multiple choice survey questions. Endorsement was obtained by the European Society of Neuroradiology, American Society of Functional Neuroradiology, and African Academy of Neurology. A link to the online questionnaire was sent to their respective members and members of the Faculty Advocating Collaborative and Thoughtful Carotid Artery Treatments (FACTCATS). The questionnaire was open from May 16 to July 16, 2019. RESULTS: The responses from 223 respondents from 46 countries were included in the analyses including 65.9% from academic university hospitals. Neuroradiologists/radiologists comprised 68.2% of respondents, followed by neurologists (15%) and vascular surgeons (12.9%). In symptomatic patients, half (50.4%) the respondents answered that the first exam they used to evaluate carotid bifurcation was ultrasound, followed by computed tomography angiography (CTA, 41.6%) and then magnetic resonance imaging (MRI 8%). In asymptomatic patients, the first exam used to evaluate carotid bifurcation was ultrasound in 88.8% of respondents, CTA in 7%, and MRA in 4.2%. The percent stenosis upon which carotid endarterectomy or stenting was recommended was reduced in the presence of imaging evidence of "vulnerable plaque features" by 66.7% respondents for symptomatic patients and 34.2% for asymptomatic patients with a smaller subset of respondents even offering procedural intervention to patients with <50% symptomatic or asymptomatic stenosis. CONCLUSIONS: We found heterogeneity in current practices of carotid stenosis imaging and management in this worldwide survey with many respondents including vulnerable plaque imaging into their decision analysis despite the lack of proven benefit from clinical trials. This study highlights the need for new clinical trials using vulnerable plaque imaging to select high-risk patients despite maximal medical therapy who may benefit from procedural intervention.

The impact of reporting magnetic resonance imaging incidental findings in the Canadian alliance for healthy hearts and minds cohort.

BACKGROUND: In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies. METHODS: Between 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported. RESULTS: Severe structural abnormalities occurred in 8.3% (95% confidence interval 7.7-8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy. CONCLUSION: The management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02220582 .

Reduced Cognitive Assessment Scores Among Individuals With Magnetic Resonance Imaging-Detected Vascular Brain Injury.

Background and Purpose- Little is known about the association between covert vascular brain injury and cognitive impairment in middle-aged populations. We investigated if scores on a cognitive screen were lower in individuals with higher cardiovascular risk, and those with covert vascular brain injury. Methods- Seven thousand five hundred forty-seven adults, aged 35 to 69 years, free of cardiovascular disease underwent a cognitive assessment using the Digital Symbol Substitution test and Montreal Cognitive Assessment, and magnetic resonance imaging (MRI) to detect covert vascular brain injury (high white matter hyperintensities, lacunar, and nonlacunar brain infarctions). Cardiovascular risk factors were quantified using the INTERHEART (A Global Study of Risk Factors for Acute Myocardial Infarction) risk score. Multivariable mixed models tested for independent determinants of reduced cognitive scores. The population attributable risk of risk factors and MRI vascular brain injury on low cognitive scores was calculated. Results- The mean age of participants was 58 (SD, 9) years; 55% were women. Montreal Cognitive Assessment and Digital Symbol Substitution test scores decreased significantly with increasing age (P<0.0001), INTERHEART risk score (P<0.0001), and among individuals with high white matter hyperintensities, nonlacunar brain infarction, and individuals with 3+ silent brain infarctions. Adjusted for age, sex, education, ethnicity covariates, Digital Symbol Substitution test was significantly lowered by 1.0 (95% CI, -1.3 to -0.7) point per 5-point cardiovascular risk score increase, 1.9 (95% CI, -3.2 to -0.6) per high white matter hyperintensities, 3.5 (95% CI, -6.4 to -0.7) per nonlacunar stroke, and 6.8 (95% CI, -11.5 to -2.2) when 3+ silent brain infarctions were present. No postsecondary education accounted for 15% (95% CI, 12-17), moderate and high levels of cardiovascular risk factors accounted for 19% (95% CI, 8-30), and MRI vascular brain injury accounted for 10% (95% CI, -3 to 22) of low test scores. Conclusions- Among a middle-aged community-dwelling population, scores on a cognitive screen were lower in individuals with higher cardiovascular risk factors or MRI vascular brain injury. Much of the population attributable risk of low cognitive scores can be attributed to lower educational attainment, higher cardiovascular risk factors, and MRI vascular brain injury.

Sample-Size Determination Methodologies for Machine Learning in Medical Imaging Research: A Systematic Review.

PURPOSE: The required training sample size for a particular machine learning (ML) model applied to medical imaging data is often unknown. The purpose of this study was to provide a descriptive review of current sample-size determination methodologies in ML applied to medical imaging and to propose recommendations for future work in the field. METHODS: We conducted a systematic literature search of articles using Medline and Embase with keywords including "machine learning," "image," and "sample size." The search included articles published between 1946 and 2018. Data regarding the ML task, sample size, and train-test pipeline were collected. RESULTS: A total of 167 articles were identified, of which 22 were included for qualitative analysis. There were only 4 studies that discussed sample-size determination methodologies, and 18 that tested the effect of sample size on model performance as part of an exploratory analysis. The observed methods could be categorized as pre hoc model-based approaches, which relied on features of the algorithm, or post hoc curve-fitting approaches requiring empirical testing to model and extrapolate algorithm performance as a function of sample size. Between studies, we observed great variability in performance testing procedures used for curve-fitting, model assessment methods, and reporting of confidence in sample sizes. CONCLUSIONS: Our study highlights the scarcity of research in training set size determination methodologies applied to ML in medical imaging, emphasizes the need to standardize current reporting practices, and guides future work in development and streamlining of pre hoc and post hoc sample size approaches.

Sharing De-identified Medical Images Electronically for Research: A Survey of Patients' Opinion Regarding Data Management.

PURPOSE: Secondary usage of patient data has recently become of increasing interest for the development and application of computer analytic techniques. Strict oversight of these data is required and the individual patients themselves are integral to providing guidance. We sought to understand patients' attitudes to sharing their imaging data for research purposes. These images could provide a great wealth of information for researchers. METHODS: Patients from the Greater Toronto Area attending Sunnybrook Health Sciences Centre for imaging (magnetic resonance imagining, computed tomography, or ultrasound) examination areas were invited to participate in an electronic survey. RESULTS: Of the 1083 patients who were approached (computed tomography 609, ultrasound 314, and magnetic resonance imaging 160), 798 (74%) agreed to take the survey. Overall median age was 60 (interquartile range = 18, Q1 = 52, Q3 = 70), 52% were women, 42% had a university degree, and 7% had no high school diploma. In terms of willingness to share de-identified medical images for research, 76% were willing (agreed and strongly agreed), while 7% refused. Most participants gave their family physicians (73%) and other physicians (57%) unconditional data access. Participants chose hospitals/research institutions to regulate electronic images databases (70%), 89% wanted safeguards against unauthorized access to their data, and over 70% wanted control over who will be permitted, for how long, and the ability to revoke that permission. CONCLUSIONS: Our study found that people are willing to share their clinically acquired de-identified medical images for research studies provided that they have control over permissions and duration of access.

A Systematic Review of Fatigue in Radiology: Is It a Problem?

OBJECTIVE: The purpose of this study was to review current literature regarding radiologist fatigue. MATERIALS AND METHODS: A literature search was performed using PubMed. Key words and Medical Subject Heading terms were used to generate refined queries with inclusion and exclusion criteria, focusing on fatigue and error. Results were selected according to these criteria: examined radiologist fatigue and radiologic error stemming from fatigue; experimental results measured as accuracy, error, or performance; and peer-reviewed publication. The risk of bias was addressed by including both quantitative and qualitative studies. RESULTS: Twenty-seven articles were included, mainly primary research articles. Common outcome measures included subjective self-reports and tests to measure eyestrain. Reaction time was also recorded, accounting for variables such as age and experience. One group recommended that guidelines should be implemented regarding number of hours worked. Most recommended ergonomic interventions, proposing the implementation of tools to measure and standardize fatigue and optimize workflow, in conjunction with considering radiologists individually. Education in appropriate viewing habits and breaks were also suggested. Only one study with seven participants recommended that radiologists should sleep well to improve their performance and overall well-being, despite the undeniable evidence that radiologists are fatigued. CONCLUSION: Fatigue is present in radiology and affects diagnostic accuracy.

Carotid Intraplaque Hemorrhage in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND: Many embolic strokes are of undetermined source (ESUS). Carotid artery intraplaque hemorrhage (IPH), an unstable component of atherosclerosis, may be an under-recognized etiology in patients with ESUS. We investigated the prevalence of carotid IPH detected noninvasively by magnetic resonance imaging (MRI). METHODS: This pilot study analyzed data from a prospective cohort of patients with a recent ESUS who underwent MRI for carotid IPH assessment. All patients had carotid artery stenosis of less than 50%. The primary outcome was the presence of carotid IPH ipsilateral to the cerebral ischemic event. RESULTS: The cohort comprised 35 consecutive patients with a recent carotid-territory ESUS who underwent carotid MRI (mean age 74.3 ± 9.6 years). We found ipsilateral and contralateral IPH in 7 of 35 patients (20.0%) and in 3 of 35 patients (8.6%), respectively (P = .005). CONCLUSIONS: In this sample of patients with ESUS, 1 in 5 had carotid IPH ipsilateral to their acute infarct, as detected by MRI of the vessel wall. Further studies are warranted to investigate carotid IPH as an etiology of ESUS.

Age-Specific Sex Differences in Magnetic Resonance Imaging-Depicted Carotid Intraplaque Hemorrhage.

BACKGROUND AND PURPOSE: Stroke rates are higher in men compared with women in the fourth through seventh decades of life, and higher rates may result from differences in carotid intraplaque hemorrhage (IPH), an unstable atherosclerotic plaque component. We report age-specific sex differences in the presence of magnetic resonance imaging-depicted carotid IPH. METHODS: Patients (n=1115) underwent magnetic resonance imaging for carotid IPH between 2005 and 2014. Low-grade carotid stenosis patients (n=906) without prior endarterectomy were eligible for this cross-sectional study. RESULTS: Of the 906 patients included (mean age±SD in years, 66.98±15.15), 63 (6.95%) had carotid IPH. In men and women, carotid IPH was present in 11.43% (48 of 420) and 3.09% (15 of 486), respectively (P<0.0001). Multivariable logistic regression analysis confirmed greater odds of carotid IPH in men for all ages: 45 to 54 (odds ratio=45.45; 95% confidence interval, 3.43-500), 55 to 64 years (odds ratio=21.74; 95% confidence interval, 3.21-142.86), 65 to 74 years (odds ratio=10.42; 95% confidence interval, 2.91-37.04), and ≥75 years (odds ratio=5.00; 95% confidence interval, 2.31-10.75). Male sex modified the effect of age on the presence of carotid IPH (ß=0.074; SE=0.036; P=0.0411). CONCLUSIONS: Men have greater age-specific odds of magnetic resonance imaging-depicted carotid IPH compared with women. With increasing age post-menopause, the odds of carotid IPH in women becomes closer to that of men. Delayed onset of carotid IPH in women, an unstable plaque component, may partly explain differential stroke rates between sexes, and further studies are warranted.

Departmental h-Index: Evidence for Publishing Less?

PURPOSE: The h-index is an established method for determining an individual faculty member's impact on the scientific literature. The purpose of this study was to measure and describe over time the combined h-index of a large university medical imaging department. MATERIALS AND METHODS: All faculty members from the Department of Medical Imaging, University of Toronto, were identified from administrative records for 6 separate years between 2000-2014. Individual members' and the departmental h-index were calculated using citation data from the Scopus database. Descriptive univariate statistics were reported. Factors contributing to the change in departmental h-index over time were assessed using linear regression analysis. RESULTS: The number of faculty members increased from 117 in 2000 to 186 in 2014. The departmental h-index increased from 48 in 2000 to 142 in 2014. During this time period, the median h-index for faculty members increased from 4 (interquartile range 2-8) to 10 (interquartile range 5-19). Regression analysis revealed that for every additional staff member, the departmental h-index increased by 1.4 (standard error = 0.1, P < .01), whereas, by increasing the median h-index of members by 1 the departmental h-index increased by 15.7 (standard error = 0.6, P < .01). CONCLUSION: Our study suggests that to increase a department's h-index, it is important to foster impactful research from within the faculty ranks of the department. The h-index of academic radiology departments is a meaningful tool that allows for evaluation from within and against other academic centres.

Rationale, design, and methods for Canadian alliance for healthy hearts and minds cohort study (CAHHM) - a Pan Canadian cohort study.

BACKGROUND: The Canadian Alliance for Healthy Hearts and Minds (CAHHM) is a pan-Canadian, prospective, multi-ethnic cohort study being conducted in Canada. The overarching objective of the CAHHM is to understand the association of socio-environmental and contextual factors (such as societal structure, activity, nutrition, social and tobacco environments, and access to health services) with cardiovascular risk factors, subclinical vascular disease, and cardiovascular and other chronic disease outcomes. METHODS/DESIGN: Participants between 35 and 69 years of age are being recruited from existing cohorts and a new First Nations Cohort to undergo a detailed assessment of health behaviours (including diet and physical activity), cognitive function, assessment of their local home and workplace environments, and their health services access and utilization. Physical measures including weight, height, waist/hip circumference, body fat percentage, and blood pressure are collected. In addition, eligible participants undergo magnetic resonance imaging (MRI) of the brain, heart, carotid artery and abdomen to detect early subclinical vascular disease and ectopic fat deposition. DISCUSSION: CAHHM is a prospective cohort study designed to investigate the impact of community level factors, individual health behaviours, and access to health services, on cognitive function, subclinical vascular disease, fat distribution, and the development of chronic diseases among adults living in Canada.

Perfusion CT for selecting patients with acute ischemic stroke for intravenous thrombolytic therapy.

PURPOSE: To determine rates of death, disability, and symptomatic intracranial hemorrhage ( SICH symptomatic ICH ) among patients with acute ischemic stroke selected for thrombolytic therapy by using perfusion computed tomography (CT) by conducting a systematic review and meta-analysis. MATERIALS AND METHODS: A search of the literature up to July 2012 was performed by using MEDLINE, EMBASE, the Cochrane Library, PubMed, and Google Scholar on terms including "brain ischemia" and "perfusion imaging." The search was unrestricted by language of publication. Two reviewers extracted study data and independently assessed the risk of study bias. Outcomes of patients selected by using perfusion CT, including case-fatality rate, favorable outcome (modified Rankin Scale [ mRS modified Rankin Scale ] score, ≤2), and rates of SICH symptomatic ICH , were estimated. RESULTS: Thirteen experimental or observational studies that included patients who received intravenous thrombolytic treatment after perfusion CT were identified. The methodologic quality of the small studies was generally good. Overall, 90-day mortality was 10.0% (95% confidence interval [ CI confidence interval ]: 5.4%, 15.9%). Among patients treated within 3 hours of symptom onset, mortality was 12.5% (95% CI confidence interval : 6.7%, 19.7%), a favorable outcome ( mRS modified Rankin Scale score, ≤2) was seen in 42.5% of patients (95% CI confidence interval : 16.6%, 70.9%), and the SICH symptomatic ICH rate was 3.3% (95% CI confidence interval : 0.7%, 7.7%). Among patients treated more than 3 hours after symptom onset, mortality was 2.9% (95% CI confidence interval : 0.0%, 12.7%), 69.9% of patients (95% CI confidence interval : 0%, 83.5%) had a favorable outcome, and the SICH symptomatic ICH rate was 3.9% (95% CI confidence interval : 0.8%, 9.2%). CONCLUSION: The outcomes (mortality, morbidity, and SICH symptomatic ICH rates) for patients selected with perfusion CT to receive intravenous thrombolytic treatment more than 3 hours after symptom onset appear favorable.

Catheter-based intramural delivery of red blood cells in an animal model of atherosclerosis.

This report demonstrates intramural red blood cell (RBC) delivery in an atherosclerotic rabbit aorta model and validates the ability of fluoroscopy and computed tomography to verify RBC deposition. A microinfusion catheter with a 35-gauge needle delivered RBCs mixed with iodinated contrast agent to the aorta wall. Six rabbits were sacrificed after injection to confirm RBC delivery. Iron deposition was examined in four additional rabbits 3-7 weeks after injection. Imaging demonstrated 86% sensitivity and 100% specificity for the detection of RBC deposition (n = 25 injection attempts). Iron deposits were found in all intraplaque injection sites 3-7 weeks after injection.

Systematic review, critical appraisal, and analysis of the quality of economic evaluations in stroke imaging.

BACKGROUND AND PURPOSE: This study reviews the quality of economic evaluations of imaging after acute stroke and identifies areas for improvement. METHODS: We performed full-text searches of electronic databases that included Medline, Econlit, the National Health Service Economic Evaluation Database, and the Tufts Cost Effectiveness Analysis Registry through July 2012. Search strategy terms included the following: stroke*; cost*; or cost-benefit analysis*; and imag*. Inclusion criteria were empirical studies published in any language that reported the results of economic evaluations of imaging interventions for patients with stroke symptoms. Study quality was assessed by a commonly used checklist (with a score range of 0% to 100%). RESULTS: Of 568 unique potential articles identified, 5 were included in the review. Four of 5 articles were explicit in their analysis perspectives, which included healthcare system payers, hospitals, and stroke services. Two studies reported results during a 5-year time horizon, and 3 studies reported lifetime results. All included the modified Rankin Scale score as an outcome measure. The median quality score was 84.4% (range=71.9%-93.5%). Most studies did not consider the possibility that patients could not tolerate contrast media or could incur contrast-induced nephropathy. Three studies compared perfusion computed tomography with unenhanced computed tomography but assumed that outcomes guided by the results of perfusion computed tomography were equivalent to outcomes guided by the results of magnetic resonance imaging or noncontrast computed tomography. CONCLUSIONS: Economic evaluations of imaging modalities after acute ischemic stroke were generally of high methodological quality. However, important radiology-specific clinical components were missing from all of these analyses.

Carotid Plaque-RADS: A Novel Stroke Risk Classification System.

BACKGROUND: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features. OBJECTIVES: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score. METHODS: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports. RESULTS: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of "stenosis." The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories. CONCLUSIONS: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.

Synthesis of diffusion-weighted MRI scalar maps from FLAIR volumes using generative adversarial networks.

Introduction: Acquisition and pre-processing pipelines for diffusion-weighted imaging (DWI) volumes are resource- and time-consuming. Generating synthetic DWI scalar maps from commonly acquired brain MRI sequences such as fluid-attenuated inversion recovery (FLAIR) could be useful for supplementing datasets. In this work we design and compare GAN-based image translation models for generating DWI scalar maps from FLAIR MRI for the first time. Methods: We evaluate a pix2pix model, two modified CycleGANs using paired and unpaired data, and a convolutional autoencoder in synthesizing DWI fractional anisotropy (FA) and mean diffusivity (MD) from whole FLAIR volumes. In total, 420 FLAIR and DWI volumes (11,957 images) from multi-center dementia and vascular disease cohorts were used for training/testing. Generated images were evaluated using two groups of metrics: (1) human perception metrics including peak signal-to-noise ratio (PSNR) and structural similarity (SSIM), (2) structural metrics including a newly proposed histogram similarity (Hist-KL) metric and mean squared error (MSE). Results: Pix2pix demonstrated the best performance both quantitatively and qualitatively with mean PSNR, SSIM, and MSE metrics of 23.41 dB, 0.8, 0.004, respectively for MD generation, and 24.05 dB, 0.78, 0.004, respectively for FA generation. The new histogram similarity metric demonstrated sensitivity to differences in fine details between generated and real images with mean pix2pix MD and FA Hist-KL metrics of 11.73 and 3.74, respectively. Detailed analysis of clinically relevant regions of white matter (WM) and gray matter (GM) in the pix2pix images also showed strong significant (p < 0.001) correlations between real and synthetic FA values in both tissue types (R = 0.714 for GM, R = 0.877 for WM). Discussion/conclusion: Our results show that pix2pix's FA and MD models had significantly better structural similarity of tissue structures and fine details than other models, including WM tracts and CSF spaces, between real and generated images. Regional analysis of synthetic volumes showed that synthetic DWI images can not only be used to supplement clinical datasets, but demonstrates potential utility in bypassing or correcting registration in data pre-processing.

Brain Age Estimation on a Dementia Cohort Using FLAIR MRI Biomarkers.

BACKGROUND AND PURPOSE: The prodromal stage of Alzheimer's disease presents an imperative intervention window. This work focuses on using brain age prediction models and biomarkers from FLAIR MR imaging to identify subjects who progress to Alzheimer's disease (converting mild cognitive impairment) or those who remain stable (stable mild cognitive impairment). MATERIALS AND METHODS: A machine learning model was trained to predict the age of normal control subjects on the basis of volume, intensity, and texture features from 3239 FLAIR MRI volumes. The brain age gap estimation (BrainAGE) was computed as the difference between the predicted and true age, and it was used as a biomarker for both cross-sectional and longitudinal analyses. Differences in biomarker means, slopes, and intercepts were investigated using ANOVA and Tukey post hoc test. Correlation analysis was performed between brain age gap estimation and established Alzheimer's disease indicators. RESULTS: The brain age prediction model showed accurate results (mean absolute error = 2.46 years) when testing on held out normal control data. The computed BrainAGE metric showed significant differences between the stable mild cognitive impairment and converting mild cognitive impairment groups in cross-sectional and longitudinal analyses, most notably showing significant differences up to 4 years before conversion to Alzheimer's disease. A significant correlation was found between BrainAGE and previously established Alzheimer's disease conversion biomarkers. CONCLUSIONS: The BrainAGE metric can allow clinicians to consider a single explainable value that summarizes all the biomarkers because it considers many dimensions of disease and can determine whether the subject has normal aging patterns or if he or she is trending into a high-risk category using a single value.

Detecting conversion from mild cognitive impairment to Alzheimer's disease using FLAIR MRI biomarkers.

Mild cognitive impairment (MCI) is the prodromal phase of Alzheimer's disease (AD) and while it presents as an imperative intervention window, it is difficult to detect which subjects convert to AD (cMCI) and which ones remain stable (sMCI). The objective of this work was to investigate fluid-attenuated inversion recovery (FLAIR) MRI biomarkers and their ability to differentiate between sMCI and cMCI subjects in cross-sectional and longitudinal data. Three types of biomarkers were investigated: volume, intensity and texture. Volume biomarkers included total brain volume, cerebrospinal fluid volume (CSF), lateral ventricular volume, white matter lesion volume, subarachnoid CSF, and grey matter (GM) and white matter (WM), all normalized to intracranial volume. The mean intensity, kurtosis, and skewness of the GM and WM made up the intensity features. Texture features quantified homogeneity and microstructural tissue changes of GM and WM regions. Composite indices were also considered, which are biomarkers that represent an aggregate sum (z-score normalization and summation) of all biomarkers. The FLAIR MRI biomarkers successfully identified high-risk subjects as significant differences (p < 0.05) were found between the means of the sMCI and cMCI groups and the rate of change over time for several individual biomarkers as well as the composite indices for both cross-sectional and longitudinal analyses. Classification accuracy and feature importance analysis showed volume biomarkers to be most predictive, however, best performance was obtained when complimenting the volume biomarkers with the intensity and texture features. Using all the biomarkers, accuracy of 86.2 % and 69.2 % was achieved for normal control-AD and sMCI-cMCI classification respectively. Survival analysis demonstrated that the majority of the biomarkers showed a noticeable impact on the AD conversion probability 4 years prior to conversion. Composite indices were the top performers for all analyses including feature importance, classification, and survival analysis. This demonstrated their ability to summarize various dimensions of disease into single-valued metrics. Significant correlation (p < 0.05) with phosphorylated-tau and amyloid-beta CSF biomarkers was found with all the FLAIR biomarkers. The proposed biomarker system is easily attained as FLAIR is routinely acquired, models are not computationally intensive and the results are explainable, thus making this pipeline easily integrated into clinical workflow.

Alzheimer's and vascular disease classification using regional texture biomarkers in FLAIR MRI.

Interactions between subcortical vascular disease and dementia due to Alzheimer's disease (AD) are unclear, and clinical overlap between the diseases makes diagnosis challenging. Existing studies have shown regional microstructural changes specific to each disease, and that textures in fluid-attenuated inversion recovery (FLAIR) MRI images may characterize abnormalities in tissue microstructure. This work aims to investigate regional FLAIR biomarkers that can differentiate dementia cohorts with and without subcortical vascular disease. FLAIR and diffusion MRI (dMRI) volumes were obtained in 65 mild cognitive impairment (MCI), 21 AD, 44 subcortical vascular MCI (scVMCI), 22 Mixed etiology, and 48 healthy elderly patients. FLAIR texture and intensity biomarkers were extracted from the normal appearing brain matter (NABM), WML penumbra, blood supply territory (BST), and white matter tract regions of each patient. All FLAIR biomarkers were correlated to dMRI metrics in each region and global WML load, and biomarker means between groups were compared using ANOVA. Binary classifications were performed using Random Forest classifiers to investigate the predictive nature of the regional biomarkers, and SHAP feature analysis was performed to further investigate optimal regions of interest for differentiating disease groups. The regional FLAIR biomarkers were strongly correlated to MD, while all biomarker regions but white matter tracts were strongly correlated to WML burden. Classification between Mixed disease and healthy, AD, and scVMCI patients yielded accuracies of 97%, 81%, and 72% respectively using WM tract biomarkers. Classification between scVMCI and healthy, MCI, and AD patients yielded accuracies of 89%, 84%, and 79% respectively using penumbra biomarkers. Only the classification between AD and healthy patients had optimal results using NABM biomarkers. This work presents novel regional FLAIR biomarkers that may quantify white matter degeneration related to subcortical vascular disease, and which indicate that investigating degeneration in specific regions may be more important than assessing global WML burden in vascular disease groups.

Segmentation of Brain Metastases Using Background Layer Statistics (BLAST).

BACKGROUND AND PURPOSE: Accurate segmentation of brain metastases is important for treatment planning and evaluating response. The aim of this study was to assess the performance of a semiautomated algorithm for brain metastases segmentation using Background Layer Statistics (BLAST). MATERIALS AND METHODS: Nineteen patients with 48 parenchymal and dural brain metastases were included. Segmentation was performed by 4 neuroradiologists and 1 radiation oncologist. K-means clustering was used to identify normal gray and white matter (background layer) in a 2D parameter space of signal intensities from postcontrast T2 FLAIR and T1 MPRAGE sequences. The background layer was subtracted and operator-defined thresholds were applied in parameter space to segment brain metastases. The remaining voxels were back-projected to visualize segmentations in image space and evaluated by the operators. Segmentation performance was measured by calculating the Dice-Sørensen coefficient and Hausdorff distance using ground truth segmentations made by the investigators. Contours derived from the segmentations were evaluated for clinical acceptance using a 5-point Likert scale. RESULTS: The median Dice-Sørensen coefficient was 0.82 for all brain metastases and 0.9 for brain metastases of ≥10 mm. The median Hausdorff distance was 1.4 mm. Excellent interreader agreement for brain metastases volumes was found with an intraclass correlation coefficient = 0.9978. The median segmentation time was 2.8 minutes/metastasis. Forty-five contours (94%) had a Likert score of 4 or 5, indicating that the contours were acceptable for treatment, requiring no changes or minor edits. CONCLUSIONS: We show accurate and reproducible segmentation of brain metastases using BLAST and demonstrate its potential as a tool for radiation planning and evaluating treatment response.