Two-Stage Classification of Future Knee Osteoarthritis Severity After 8 Years Using MRI: Data from the Osteoarthritis Initiative.

Currently, there are no methods or tools available in clinical practice for classifying future knee osteoarthritis (KOA). In this study, we aimed to fill this gap by classifying future KOA into three severity grades: KL01 (healthy), KL2 (moderate), and KL34 (severe) based on the Kellgren-Lawrance scale. Due to the complex nature of multiclass classification, we used a two-stage method, which separates the classification task into two binary classifications (KL01 vs. KL234 in the first stage and KL2 vs. KL34 in the second stage). Our machine learning (ML) model used two Balanced Random Forest algorithms and was trained with gender, age, height, weight, and quantitative knee morphology obtained from magnetic resonance imaging. Our training dataset comprised longitudinal 8-year follow-up data of 1213 knees from the Osteoarthritis Initiative. Through extensive experimentation with various feature combinations, we identified KL baseline and weight as the most essential features, while gender surprisingly proved to be one of the least influential feature. Our best classification model generated a weighted F1 score of 79.0% and a balanced accuracy of 65.9%. The area under the receiver operating characteristic curve was 83.0% for healthy (KL01) versus moderate (KL2) or severe (KL34) KOA patients and 86.6% for moderate (KL2) versus severe (KL34) KOA patients. We found a statistically significant difference in performance between our two-stage classification model and the traditional single-stage classification model. These findings demonstrate the encouraging results of our two-stage classification model for multiclass KOA severity classification, suggesting its potential application in clinical settings in future.

Intelligence and cortical morphometry: caveats in brain-behavior associations.

It is well-established that brain size is associated with intelligence. But the relationship between cortical morphometric measures and intelligence is unclear. Studies have produced conflicting results or no significant relations between intelligence and cortical morphometric measures such as cortical thickness and peri-cortical contrast. This discrepancy may be due to multicollinearity amongst the independent variables in a multivariate regression analysis, or a failure to fully account for the relationship between brain size and intelligence in some other way. Our study shows that neither cortical thickness nor peri-cortical contrast reliably improves IQ prediction accuracy beyond what is achieved with brain volume alone. We show this in multiple datasets, with child data, developmental data, and with adult data; we show this with data acquired either at multiple sites, or at a single site; we show this with data acquired with different MRI scanner manufacturers, or with all data acquired on a single scanner; and we show this with fluid intelligence, full-scale IQ, performance IQ, and verbal IQ. But our point is not really even about IQ; rather we proffer a methodological caveat and potential explanation of the discrepancies in previous results, and which applies broadly.

ComBating inter-site differences in field strength: harmonizing preclinical traumatic brain injury MRI data.

Integrating datasets from multiple sites and scanners can increase statistical power for neuroimaging studies but can also introduce significant inter-site confounds. We evaluated the effectiveness of ComBat, an empirical Bayes approach, to combine longitudinal preclinical MRI data acquired at 4.7 or 9.4 T at two different sites in Australia. Male Sprague Dawley rats underwent MRI on Days 2, 9, 28, and 150 following moderate/severe traumatic brain injury (TBI) or sham injury as part of Project 1 of the NIH/NINDS-funded Centre Without Walls EpiBioS4Rx project. Diffusion-weighted and multiple-gradient-echo images were acquired, and outcomes included QSM, FA, and ADC. Acute injury measures including apnea and self-righting reflex were consistent between sites. Mixed-effect analysis of ipsilateral and contralateral corpus callosum (CC) summary values revealed a significant effect of site on FA and ADC values, which was removed following ComBat harmonization. Bland-Altman plots for each metric showed reduced variability across sites following ComBat harmonization, including for QSM, despite appearing to be largely unaffected by inter-site differences and no effect of site observed. Following harmonization, the combined inter-site data revealed significant differences in the imaging metrics consistent with previously reported outcomes. TBI resulted in significantly reduced FA and increased susceptibility in the ipsilateral CC, and significantly reduced FA in the contralateral CC compared with sham-injured rats. Additionally, TBI rats also exhibited a reversal in ipsilateral CC ADC values over time with significantly reduced ADC at Day 9, followed by increased ADC 150 days after injury. Our findings demonstrate the need for harmonizing multi-site preclinical MRI data and show that this can be successfully achieved using ComBat while preserving phenotypical changes due to TBI.

Estimating Dementia Onset: AT(N) Profiles and Predictive Modeling in Mild Cognitive Impairment Patients.

BACKGROUND: Mild Cognitive Impairment (MCI) usually precedes the symptomatic phase of dementia and constitutes a window of opportunities for preventive therapies. OBJECTIVES: The objective of this study was to predict the time an MCI patient has left to reach dementia and obtain the most likely natural history in the progression of MCI towards dementia. METHODS: This study was conducted on 633 MCI patients and 145 subjects with dementia through 4726 visits over 15 years from Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. A combination of data from AT(N) profiles at baseline and longitudinal predictive modeling was applied. A data-driven approach was proposed for categorical diagnosis prediction and timeline estimation of cognitive decline progression, which combined supervised and unsupervised learning techniques. RESULTS: A reduced vector of only neuropsychological measures was selected for training the models. At baseline, this approach had high performance in detecting subjects at high risk of converting from MCI to dementia in the coming years. Furthermore, a Disease Progression Model (DPM) was built and also verified using three metrics. As a result of the DPM focused on the studied population, it was inferred that amyloid pathology (A+) appears about 7 years before dementia, and tau pathology (T+) and neurodegeneration (N+) occur almost simultaneously, between 3 and 4 years before dementia. In addition, MCI-A+ subjects were shown to progress more rapidly to dementia compared to MCI-A- subjects. CONCLUSION: Based on proposed natural histories and cross-sectional and longitudinal analysis of AD markers, the results indicated that only a single cerebrospinal fluid sample is necessary during the prodromal phase of AD. Prediction from MCI into dementia and its timeline can be achieved exclusively through neuropsychological measures.

Machine learning prediction of future amyloid beta positivity in amyloid-negative individuals.

BACKGROUND: The pathophysiology of Alzheimer's disease (AD) involves ß -amyloid (A ß ) accumulation. Early identification of individuals with abnormal ß -amyloid levels is crucial, but A ß quantification with positron emission tomography (PET) and cerebrospinal fluid (CSF) is invasive and expensive. METHODS: We propose a machine learning framework using standard non-invasive (MRI, demographics, APOE, neuropsychology) measures to predict future A ß -positivity in A ß -negative individuals. We separately study A ß -positivity defined by PET and CSF. RESULTS: Cross-validated AUC for 4-year A ß conversion prediction was 0.78 for the CSF-based and 0.68 for the PET-based A ß definitions. Although not trained for the clinical status-change prediction, the CSF-based model excelled in predicting future mild cognitive impairment (MCI)/dementia conversion in cognitively normal/MCI individuals (AUCs, respectively, 0.76 and 0.89 with a separate dataset). CONCLUSION: Standard measures have potential in detecting future A ß -positivity and assessing conversion risk, even in cognitively normal individuals. The CSF-based definition led to better predictions than the PET-based definition.

Volume electron microscopy in injured rat brain validates white matter microstructure metrics from diffusion MRI.

Biophysical modeling of diffusion MRI (dMRI) offers the exciting potential of bridging the gap between the macroscopic MRI resolution and microscopic cellular features, effectively turning the MRI scanner into a noninvasive in vivo microscope. In brain white matter, the Standard Model (SM) interprets the dMRI signal in terms of axon dispersion, intra- and extra-axonal water fractions and diffusivities. However, for SM to be fully applicable and correctly interpreted, it needs to be carefully evaluated using histology. Here, we perform a comprehensive histological validation of the SM parameters, by characterizing WM microstructure in sham and injured rat brains using volume (3d) electron microscopy (EM) and ex vivo dMRI. Sensitivity is evaluated by how close each SM metric is to its histological counterpart, and specificity by how independent it is from other, non-corresponding histological features. This comparison reveals that SM is sensitive and specific to microscopic properties, clearing the way for the clinical adoption of in vivo dMRI derived SM parameters as biomarkers for neurological disorders.