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BACKGROUND: Elevated renin has been shown to predict poor response to standard vasoactive therapies and is associated with poor outcomes in adults. Similarly, elevated renin was associated with mortality in children with septic shock. Renin concentration profiles after pediatric cardiac surgery are unknown. The purpose of this study was to characterize renin kinetics after pediatric cardiac surgery. METHODS: Single-center retrospective study of infants who underwent cardiac surgery with cardiopulmonary bypass (CPB) utilizing serum samples obtained in the perioperative period to measure plasma renin concentrations (pg/mL). Time points included pre-bypass and 1, 4, and 24â h after initiation of CPB. RESULTS: Fifty patients (65% male) with a median age 5 months (interquartile range (IQR) 3.5, 6.5) were included. Renin concentrations peaked 4â h after CPB. There was a significant difference in preoperative and 4â h post-CPB renin concentration (4â h post-CPB vs preoperative: mean difference 100.6, 95% confidence interval (CI) 48.9-152.4, P < .001). Median renin concentration at 24â h after CPB was lower than the preoperative baseline. CONCLUSIONS: We describe renin kinetics in infants after CPB. Future studies based on these data can now be performed to evaluate the associations of elevated renin concentrations with adverse outcomes.
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OBJECTIVE: To assess discharge readiness and clinical engagement post-discharge in families of children undergoing congenital heart surgery. STUDY DESIGN: This prospective cross-sectional study was performed at a major tertiary pediatric cardiac referral center. Eligible parents and caregivers completed a discharge readiness tool, the Readiness for Hospital Discharge Scale for Parents of Hospitalized Children, via online survey on the day of discharge. Clinical engagement data included subsequent phone calls, clinic visits, emergency department visits, and hospital readmissions. Readiness for Hospital Discharge Scale for Parents of Hospitalized Children scores were measured as follows: very high (9-10), high (8-8.9), moderate (7-7.9), and low (<7). Descriptive statistics were used to describe demographic data. RESULTS: In total, 128 families enrolled between April and December 2021. Parent discharge readiness scores ranged from "high" to "very high." Families with lower socioeconomic status and younger patients (especially single-ventricle infants or "interstage") had a greater proportion of clinic visits, emergency department visits, and hospital readmissions within 30-days postdischarge compared with other groups. CONCLUSIONS: Discharge readiness scores were not associated with clinical engagement. We identified vulnerable populations as evidenced by a greater frequency of clinical engagement in the immediate postoperative period, particularly younger patients and first-time surgeries. Although these visits may be appropriate, novel programs could enhance education and emotional support to prevent delay in seeking care or creating excessive stress and anxiety after discharge.
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Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Lactante , Humanos , Niño , Alta del Paciente , Cuidados Posteriores , Estudios Prospectivos , Estudios Transversales , Padres/psicología , Cardiopatías Congénitas/cirugíaRESUMEN
Entrustable professional activities (EPAs) have become a popular framework for medical trainee assessment and a supplemental component for milestone and competency assessment. EPAs were developed to facilitate assessment of competencies and furthermore to facilitate translation into clinical practice. In this review, we explore the rationale for the introduction of EPAs, examine whether they fulfill the promise expected of them, and contemplate further developments in their application with specific reference to training in pediatric cardiology.
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Cardiología , Internado y Residencia , Niño , Humanos , Competencia Clínica , Educación Basada en Competencias , Educación de Postgrado en MedicinaRESUMEN
Entrustable professional activities (EPAs) are "observable essential tasks expected to be performed by a physician for safe patient care in practice." Six Pediatric Cardiology (PC) EPAs and their level of supervision (LOS) scales were developed by medical educators in PC using a modified Delphi process and reviewed by the Subspecialty Pediatrics Investigator Network (SPIN). However, their general use in assessment for PC fellows for graduation requirements has yet to be studied. The objective of this study was to determine the minimum LOS required for PC fellows to graduate and compare it with the minimum LOS expected for safe and effective practice for the six PC EPAs, from the perspective of the PC Fellowship Program Directors(FPD). All Fellowship Program Directors(FPD) of ACGME-accredited PC fellowships were surveyed through SPIN between April 2017 and August 2017. For each of the PC EPAs, the FPDs were asked to indicate the minimum LOS expected for graduation and whether they would allow a fellow to graduate if this level was not achieved and the minimum LOS expected for a practicing pediatric cardiologist to provide safe and effective patient care. The minimum LOS was defined as the LOS for which no more than 20% of FPDs would want a lower level. The survey response rate was 80% (47/59). The majority of the FPDs did not require a minimum LOS of five corresponding to unsupervised practice in any of the six PC EPAs at graduation. For EPAs related to imaging, arrhythmia management, and management of cardiac problems, the minimum LOS for graduation was 3, corresponding to being "trusted to perform a task with indirect supervision for most simple and a few complex cases." For the EPAs related to interventional cardiology, heart failure pulmonary hypertension, and cardiac intensive care, the minimum LOS for graduation was 2, corresponding to being "trusted to perform a task only with direct supervision and coaching." The minimum LOS considered necessary for safe and effective practice for all but one EPA was 3. For the EPA related to the management of cardiac problems, the minimum LOS for safe practice was 4, corresponding to being "trusted to execute tasks independently except for few complex and critical cases." Most PC FPDs reported they would not require fellows to achieve the highest entrustment level for any of the six PC EPAs for graduation. It is crucial that educational programs evolve to address these essential activities during training better and that stakeholders ensure that graduating PC fellows have adequate resources and infrastructure to continue professional development as early career pediatric cardiologists.
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Recombinant angiotensin II is an emerging drug therapy for refractory hypotension. Its use is relevant to patients with disruption of the renin-angiotensin-aldosterone system denoted by elevated direct renin levels. We present a child that responded to recombinant angiotensin II in the setting of right ventricular hypertension and multi-organism septic shock.
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Cardiopatías , Sepsis , Humanos , Niño , Angiotensina II , Hemodinámica , CandidaRESUMEN
OBJECTIVE: Despite a recent focus on the preferential use of ultrasound over CT for pediatric appendicitis, most children transferred from community hospitals still undergo diagnostic CT scans. The purpose of this study was to evaluate CT techniques performed for children with acute appendicitis at nonpediatric treatment centers. MATERIALS AND METHODS: All patients treated for acute appendicitis at our tertiary-care pediatric hospital from July 1, 2011, through June 30, 2012, were identified. Patient demographics, imaging modality used to diagnoses appendicitis (CT or ultrasound), location (home or referral institution), and CT technique parameters were collected. The estimated mean organ radiation dose, number of imaging phases, and use of contrast media were evaluated at home and referral institutions. RESULTS: During the study period, 1215 patients underwent appendectomies after imaging, with 442 (36.4%) imaged at referral facilities. Most referral patients received a diagnosis by CT (n=384, 87%), compared with 73 of 773 (9.4%) who received a diagnosis by CT at the home institution. The estimated mean (±SD) organ radiation dose was not statistically significantly different between home and referral institutions (13.5±7.3 vs 12.9±6.4 mGy; p=0.58) for single-phase examinations. Of 384 referral patients, 344 had images available for review. In total, 40% (138/344) of patients from referral centers were imaged with suboptimal CT techniques: 50 delayed phase only, 52 dual phase (eight of which were imaged twice in delayed phase), eight triple phase, and 36 without IV contrast agent. CONCLUSION: CT parameters and radiation doses from single-phase examinations in children with appendicitis were similar at nonpediatric treatment centers and a tertiary care children's hospital. Future educational outreach should focus on optimizing other technical parameters.
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Apendicitis/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adolescente , Apendicectomía , Apendicitis/cirugía , Niño , Preescolar , Medios de Contraste , Femenino , Hospitales Comunitarios , Hospitales Pediátricos , Humanos , Lactante , Masculino , Dosis de Radiación , Derivación y Consulta/estadística & datos numéricos , Estudios Retrospectivos , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
BACKGROUND: Hospitalized infants>1 y old often require central venous catheters (CVC) for prolonged therapy. There are limited data describing the complication profile for this young population. The purpose of this study was to review outcomes associated with CVC insertion in this high-risk group and compare them to those in older children to develop directed quality improvement projects. MATERIALS AND METHODS: Patients receiving their first CVC, a tunneled central line or port-a-cath, from 2007-2010 were included. Femoral, non-tunneled, and hemodialysis catheters were excluded. Patients aged 0-12.0 mo (infants) were compared with those 12.1-36 mo (toddlers). Complications (<30 d) included infection, malposition, malfunction, intraoperative, and the need for operative exchange. Statistical analysis included Student t-test, chi-square, and a Kaplan-Meier survival analysis. RESULTS: We identified 115 infants and 129 toddlers who underwent CVC insertion during the study period. Complication rates were higher in the infant group than in the toddler group, as was the operative exchange rate. Higher infection rates in the infant group appeared to contribute to the difference in early complications and exchange rates. A survival analysis indicated improved catheter duration in toddlers (P=0.001). CONCLUSIONS: In this cohort study, infants had a higher early complication rate, mostly attributable to infection, than their older counterparts. This difference could be explained by increased use of a tunneled central line for daily total parented nutrition in infants with gastrointestinal anomalies, as opposed to port-a-cath for chemotherapy infusion in older children. These data have prompted a number of targeted quality improvement initiatives to address relevant complications in this infant population.
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Cateterismo Venoso Central/efectos adversos , Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Venoso Central/mortalidad , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , MasculinoRESUMEN
BACKGROUND: Gastrostomy tubes are often dislodged or exchanged in children. Indications for fluoroscopic examination of gastrostomy location include concern for malposition, dislodgement, leak, or gastric outlet obstruction. We hypothesized that most of the studies obtained at our institution were not ordered for one of the aforementioned indications and do not ultimately affect patient management. METHODS: All fluoroscopic gastrostomy studies performed from January 2011 to December 2012 were reviewed. Transgastric jejunostomy studies were excluded. Patient demographics, indications for the study, elapsed time since placement, imaging findings, and short-term outcomes were recorded. Chi-square analysis was used to evaluate relationships between categorical variables. RESULTS: During the study period, 337 patients who underwent fluoroscopic gastrostomy studies were identified; median age was 2.5 y (0.05-23.8). Sixty-two percent (208/337) of the studies were ordered in asymptomatic patients to confirm tube placement location after routine exchange or replacement. Symptomatic patients accounted for 38% of the studies. Ordering physicians were primarily nonsurgeons (72%, 242/337). Abnormal findings were observed in 4.8% (16/337) of patients, six (1.7%) of whom required an operative intervention. The 2.9% (6/208) abnormal study rate for asymptomatic patients was significantly lower than the 7.9% (10/129) rate in the patients who were evaluated for symptomatic indications (P = 0.03). CONCLUSIONS: Most of the fluoroscopic gastrostomy studies ordered at a tertiary care center did not appear to alter patient care. Development of a standardized management algorithm based on clinical indications is necessary to decrease the number of extraneous gastrostomy studies.
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Gastrostomía/efectos adversos , Hospitales Pediátricos/estadística & datos numéricos , Radiografía Abdominal/estadística & datos numéricos , Procedimientos Innecesarios/estadística & datos numéricos , Adolescente , Niño , Preescolar , Fluoroscopía/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Adulto JovenRESUMEN
White matter signals in resting state blood oxygen level dependent functional magnetic resonance (BOLD-fMRI) have been largely discounted, yet there is growing evidence that these signals are indicative of brain activity. Understanding how these white matter signals capture function can provide insight into brain physiology. Moreover, functional signals could potentially be used as early markers for neurological changes, such as in Alzheimer's Disease. To investigate white matter brain networks, we leveraged the OASIS-3 dataset to extract white matter signals from resting state BOLD-FMRI data on 711 subjects. The imaging was longitudinal with a total of 2,026 images. Hierarchical clustering was performed to investigate clusters of voxel-level correlations on the timeseries data. The stability of clusters was measured with the average Dice coefficients on two different cross fold validations. The first validated the stability between scans, and the second validated the stability between subject populations. Functional clusters at hierarchical levels 4, 9, 13, 18, and 24 had local maximum stability, suggesting better clustered white matter. In comparison with JHU-DTI-SS Type-I Atlas defined regions, clusters at lower hierarchical levels identified well defined anatomical lobes. At higher hierarchical levels, functional clusters mapped motor and memory functional regions, identifying 50.00%, 20.00%, 27.27%, and 35.14% of the frontal, occipital, parietal, and temporal lobe regions respectively.
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Purpose: In brain diffusion magnetic resonance imaging (dMRI), the volumetric and bundle analyses of whole-brain tissue microstructure and connectivity can be severely impeded by an incomplete field of view (FOV). We aim to develop a method for imputing the missing slices directly from existing dMRI scans with an incomplete FOV. We hypothesize that the imputed image with a complete FOV can improve whole-brain tractography for corrupted data with an incomplete FOV. Therefore, our approach provides a desirable alternative to discarding the valuable brain dMRI data, enabling subsequent tractography analyses that would otherwise be challenging or unattainable with corrupted data. Approach: We propose a framework based on a deep generative model that estimates the absent brain regions in dMRI scans with an incomplete FOV. The model is capable of learning both the diffusion characteristics in diffusion-weighted images (DWIs) and the anatomical features evident in the corresponding structural images for efficiently imputing missing slices of DWIs in the incomplete part of the FOV. Results: For evaluating the imputed slices, on the Wisconsin Registry for Alzheimer's Prevention (WRAP) dataset, the proposed framework achieved PSNR b 0 = 22.397 , SSIM b 0 = 0.905 , PSNR b 1300 = 22.479 , and SSIM b 1300 = 0.893 ; on the National Alzheimer's Coordinating Center (NACC) dataset, it achieved PSNR b 0 = 21.304 , SSIM b 0 = 0.892 , PSNR b 1300 = 21.599 , and SSIM b 1300 = 0.877 . The proposed framework improved the tractography accuracy, as demonstrated by an increased average Dice score for 72 tracts ( p < 0.001 ) on both the WRAP and NACC datasets. Conclusions: Results suggest that the proposed framework achieved sufficient imputation performance in brain dMRI data with an incomplete FOV for improving whole-brain tractography, thereby repairing the corrupted data. Our approach achieved more accurate whole-brain tractography results with an extended and complete FOV and reduced the uncertainty when analyzing bundles associated with Alzheimer's disease.
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To date, there has been no comprehensive study characterizing the effect of diffusion-weighted magnetic resonance imaging voxel resolution on the resulting connectome for high resolution subject data. Similarity in results improved with higher resolution, even after initial down-sampling. To ensure robust tractography and connectomes, resample data to 1 mm isotropic resolution.
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Data harmonization is necessary for removing confounding effects in multi-site diffusion image analysis. One such harmonization method, LinearRISH, scales rotationally invariant spherical harmonic (RISH) features from one site ("target") to the second ("reference") to reduce confounding scanner effects. However, reference and target site designations are not arbitrary and resultant diffusion metrics (fractional anisotropy, mean diffusivity) are biased by this choice. In this work we propose MidRISH: rather than scaling reference RISH features to target RISH features, we project both sites to a mid-space. We validate MidRISH with the following experiments: harmonizing scanner differences from 37 matched patients free of cognitive impairment, and harmonizing acquisition and study differences on 117 matched patients free of cognitive impairment. We find that MidRISH reduces bias of reference selection while preserving harmonization efficacy of LinearRISH. Users should be cautious when performing LinearRISH harmonization. To select a reference site is to choose diffusion metric effect-size. Our proposed method eliminates the bias-inducing site selection step.
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Algoritmos , Humanos , Femenino , Masculino , Procesamiento de Imagen Asistido por Computador/métodos , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Anisotropía , Anciano , Persona de Mediana Edad , Imagen de Difusión Tensora/métodos , Disfunción Cognitiva/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
Background: As large analyses merge data across sites, a deeper understanding of variance in statistical assessment across the sources of data becomes critical for valid analyses. Diffusion tensor imaging (DTI) exhibits spatially varying and correlated noise, so care must be taken with distributional assumptions. Purpose: We characterize the role of physiology, subject compliance, and the interaction of subject with the scanner in the understanding of DTI variability, as modeled in spatial variance of derived metrics in homogeneous regions. Methods: We analyze DTI data from 1035 subjects in the Baltimore Longitudinal Study of Aging (BLSA), with ages ranging from 22.4 to 103 years old. For each subject, up to 12 longitudinal sessions were conducted. We assess variance of DTI scalars within regions of interest (ROIs) defined by four segmentation methods and investigate the relationships between the variance and covariates, including baseline age, time from the baseline (referred to as "interval"), motion, sex, and whether it is the first scan or the second scan in the session. Results: Covariate effects are heterogeneous and bilaterally symmetric across ROIs. Inter-session interval is positively related (p ⪠0.001) to FA variance in the cuneus and occipital gyrus, but negatively (p ⪠0.001) in the caudate nucleus. Males show significantly (p ⪠0.001) higher FA variance in the right putamen, thalamus, body of the corpus callosum, and cingulate gyrus. In 62 out of 176 ROIs defined by the Eve type-1 atlas, an increase in motion is associated (p < 0.05) with a decrease in FA variance. Head motion increases during the rescan of DTI (Δµ = 0.045 millimeters per volume). Conclusions: The effects of each covariate on DTI variance, and their relationships across ROIs are complex. Ultimately, we encourage researchers to include estimates of variance when sharing data and consider models of heteroscedasticity in analysis. This work provides a foundation for study planning to account for regional variations in metric variance.
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Purpose: As large analyses merge data across sites, a deeper understanding of variance in statistical assessment across the sources of data becomes critical for valid analyses. Diffusion tensor imaging (DTI) exhibits spatially varying and correlated noise, so care must be taken with distributional assumptions. Here, we characterize the role of physiology, subject compliance, and the interaction of the subject with the scanner in the understanding of DTI variability, as modeled in the spatial variance of derived metrics in homogeneous regions. Approach: We analyze DTI data from 1035 subjects in the Baltimore Longitudinal Study of Aging, with ages ranging from 22.4 to 103 years old. For each subject, up to 12 longitudinal sessions were conducted. We assess the variance of DTI scalars within regions of interest (ROIs) defined by four segmentation methods and investigate the relationships between the variance and covariates, including baseline age, time from the baseline (referred to as "interval"), motion, sex, and whether it is the first scan or the second scan in the session. Results: Covariate effects are heterogeneous and bilaterally symmetric across ROIs. Inter-session interval is positively related ( p ⪠0.001 ) to FA variance in the cuneus and occipital gyrus, but negatively ( p ⪠0.001 ) in the caudate nucleus. Males show significantly ( p ⪠0.001 ) higher FA variance in the right putamen, thalamus, body of the corpus callosum, and cingulate gyrus. In 62 out of 176 ROIs defined by the Eve type-1 atlas, an increase in motion is associated ( p < 0.05 ) with a decrease in FA variance. Head motion increases during the rescan of DTI ( Δ µ = 0.045 mm per volume). Conclusions: The effects of each covariate on DTI variance and their relationships across ROIs are complex. Ultimately, we encourage researchers to include estimates of variance when sharing data and consider models of heteroscedasticity in analysis. This work provides a foundation for study planning to account for regional variations in metric variance.
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BACKGROUND: Junctional ectopic tachycardia (JET) complicates congenital heart surgery in 2% to 8.3% of cases. JET is associated with postoperative morbidity in single-center studies. We used the Pediatric Cardiac Critical Care Consortium data registry to provide a multicenter epidemiologic description of treated JET. METHODS: This is a retrospective study (February 2019-August 2022) of patients with treated JET. Inclusion criteria were (1) <12 months old at the index operation, and (2) treated for JET <72 hours after surgery. Diagnosis was defined by receiving treatment (pacing, cooling, and medications). A multilevel logistic regression analysis with hospital random effect identified JET risk factors. Impact of JET on outcomes was estimated by margins/attributable risk analysis using previous risk-adjustment models. RESULTS: Among 24,073 patients from 63 centers, 1436 (6.0%) were treated for JET with significant center variability (0% to 17.9%). Median time to onset was 3.4 hours, with 34% present on admission. Median duration was 2 days (interquartile range, 1-4 days). Tetralogy of Fallot, atrioventricular canal, and ventricular septal defect repair represented >50% of JET. Patient characteristics independently associated with JET included neonatal age, Asian race, cardiopulmonary bypass time, open sternum, and early postoperative inotropic agents. JET was associated with increased risk-adjusted durations of mechanical ventilation (incidence rate ratio, 1.6; 95% CI, 1.5-1.7) and intensive care unit length of stay (incidence rate ratio, 1.3; 95% CI, 1.2-1.3), but not mortality. CONCLUSIONS: JET is treated in 6% of patients with substantial center variability. JET contributes to increased use of postoperative resources. High center variability warrants further study to identify potential modifiable factors that could serve as targets for improvement efforts to ameliorate deleterious outcomes.
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Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Complicaciones Posoperatorias , Taquicardia Ectópica de Unión , Humanos , Taquicardia Ectópica de Unión/epidemiología , Taquicardia Ectópica de Unión/etiología , Estudios Retrospectivos , Lactante , Femenino , Masculino , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Cardiopatías Congénitas/cirugía , Recién Nacido , Incidencia , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
T1-weighted (T1w) MRI has low frequency intensity artifacts due to magnetic field inhomogeneities. Removal of these biases in T1w MRI images is a critical preprocessing step to ensure spatially consistent image interpretation. N4ITK bias field correction, the current state-of-the-art, is implemented in such a way that makes it difficult to port between different pipelines and workflows, thus making it hard to reimplement and reproduce results across local, cloud, and edge platforms. Moreover, N4ITK is opaque to optimization before and after its application, meaning that methodological development must work around the inhomogeneity correction step. Given the importance of bias fields correction in structural preprocessing and flexible implementation, we pursue a deep learning approximation / reinterpretation of the N4ITK bias fields correction to create a method which is portable, flexible, and fully differentiable. In this paper, we trained a deep learning network "DeepN4" on eight independent cohorts from 72 different scanners and age ranges with N4ITK-corrected T1w MRI and bias field for supervision in log space. We found that we can closely approximate N4ITK bias fields correction with naïve networks. We evaluate the peak signal to noise ratio (PSNR) in test dataset against the N4ITK corrected images. The median PSNR of corrected images between N4ITK and DeepN4 was 47.96 dB. In addition, we assess the DeepN4 model on eight additional external datasets and show the generalizability of the approach. This study establishes that incompatible N4ITK preprocessing steps can be closely approximated by naïve deep neural networks, facilitating more flexibility. All code and models are released at https://github.com/MASILab/DeepN4 .
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Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Algoritmos , Redes Neurales de la Computación , SesgoRESUMEN
Connectivity matrices derived from diffusion MRI (dMRI) provide an interpretable and generalizable way of understanding the human brain connectome. However, dMRI suffers from inter-site and between-scanner variation, which impedes analysis across datasets to improve robustness and reproducibility of results. To evaluate different harmonization approaches on connectivity matrices, we compared graph measures derived from these matrices before and after applying three harmonization techniques: mean shift, ComBat, and CycleGAN. The sample comprises 168 age-matched, sex-matched normal subjects from two studies: the Vanderbilt Memory and Aging Project (VMAP) and the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD). First, we plotted the graph measures and used coefficient of variation (CoV) and the Mann-Whitney U test to evaluate different methods' effectiveness in removing site effects on the matrices and the derived graph measures. ComBat effectively eliminated site effects for global efficiency and modularity and outperformed the other two methods. However, all methods exhibited poor performance when harmonizing average betweenness centrality. Second, we tested whether our harmonization methods preserved correlations between age and graph measures. All methods except for CycleGAN in one direction improved correlations between age and global efficiency and between age and modularity from insignificant to significant with p-values less than 0.05.
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Purpose: Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that provides unique information about white matter microstructure in the brain but is susceptible to confounding effects introduced by scanner or acquisition differences. ComBat is a leading approach for addressing these site biases. However, despite its frequent use for harmonization, ComBat's robustness toward site dissimilarities and overall cohort size have not yet been evaluated in terms of DTI. Approach: As a baseline, we match N=358 participants from two sites to create a "silver standard" that simulates a cohort for multi-site harmonization. Across sites, we harmonize mean fractional anisotropy and mean diffusivity, calculated using participant DTI data, for the regions of interest defined by the JHU EVE-Type III atlas. We bootstrap 10 iterations at 19 levels of total sample size, 10 levels of sample size imbalance between sites, and 6 levels of mean age difference between sites to quantify (i) ßAGE, the linear regression coefficient of the relationship between FA and age; (ii) γ/f*, the ComBat-estimated site-shift; and (iii) δ/f*, the ComBat-estimated site-scaling. We characterize the reliability of ComBat by evaluating the root mean squared error in these three metrics and examine if there is a correlation between the reliability of ComBat and a violation of assumptions. Results: ComBat remains well behaved for ßAGE when N>162 and when the mean age difference is less than 4 years. The assumptions of the ComBat model regarding the normality of residual distributions are not violated as the model becomes unstable. Conclusion: Prior to harmonization of DTI data with ComBat, the input cohort should be examined for size and covariate distributions of each site. Direct assessment of residual distributions is less informative on stability than bootstrap analysis. We caution use ComBat of in situations that do not conform to the above thresholds.
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Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural magnetic resonance imaging (MRI) data has become an important proxy task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest (ROIs). The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 ± 0.19 years for cognitively normal participants and MAE of 6.62 ± 0.30 years for cognitively impaired participants, while the second method achieves MAE of 4.69 ± 0.23 years for cognitively normal participants and MAE of 4.96 ± 0.28 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.
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INTRODUCTION: The effects of sex, race, and Apolipoprotein E (APOE) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. METHODS: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. RESULTS: Sex differences in FAFWcorr in association and projection tracts, racial differences in FAFWcorr in projection tracts, and APOE-ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. DISCUSSION: There are prominent differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.