Assessing brain involvement in Fabry disease with deep learning and the brain-age paradigm.

While neurological manifestations are core features of Fabry disease (FD), quantitative neuroimaging biomarkers allowing to measure brain involvement are lacking. We used deep learning and the brain-age paradigm to assess whether FD patients' brains appear older than normal and to validate brain-predicted age difference (brain-PAD) as a possible disease severity biomarker. MRI scans of FD patients and healthy controls (HCs) from a single Institution were, retrospectively, studied. The Fabry stabilization index (FASTEX) was recorded as a measure of disease severity. Using minimally preprocessed 3D T1-weighted brain scans of healthy subjects from eight publicly available sources (N = 2160; mean age = 33 years [range 4-86]), we trained a model predicting chronological age based on a DenseNet architecture and used it to generate brain-age predictions in the internal cohort. Within a linear modeling framework, brain-PAD was tested for age/sex-adjusted associations with diagnostic group (FD vs. HC), FASTEX score, and both global and voxel-level neuroimaging measures. We studied 52 FD patients (40.6 ± 12.6 years; 28F) and 58 HC (38.4 ± 13.4 years; 28F). The brain-age model achieved accurate out-of-sample performance (mean absolute error = 4.01 years, R2 = .90). FD patients had significantly higher brain-PAD than HC (estimated marginal means: 3.1 vs. -0.1, p = .01). Brain-PAD was associated with FASTEX score (B = 0.10, p = .02), brain parenchymal fraction (B = -153.50, p = .001), white matter hyperintensities load (B = 0.85, p = .01), and tissue volume reduction throughout the brain. We demonstrated that FD patients' brains appear older than normal. Brain-PAD correlates with FD-related multi-organ damage and is influenced by both global brain volume and white matter hyperintensities, offering a comprehensive biomarker of (neurological) disease severity.

CHARON: An Imaging-Based Diagnostic Algorithm to Navigate Through the Sea of Hereditary Degenerative Ataxias.

The complexity in diagnosing hereditary degenerative ataxias lies not only in their rarity, but also in the variety of different genetic conditions that can determine sometimes similar and overlapping clinical findings. In this light, Magnetic Resonance Imaging (MRI) plays a key role in the evaluation of these conditions, being a fundamental diagnostic tool needed not only to exclude other causes determining the observed clinical phenotype, but also to proper guide to an adequate genetic testing. Here, we propose an MRI-based diagnostic algorithm named CHARON (Characterization of Hereditary Ataxias Relying On Neuroimaging), to help in disentangling among the numerous, and apparently very similar, hereditary degenerative ataxias. Being conceived from a neuroradiological standpoint, it is based primarily on an accurate evaluation of the observed MRI findings, with the first and most important being the pattern of cerebellar atrophy. Along with the evaluation of the presence, or absence, of additional signal changes and/or supratentorial involvement, CHARON allows for the identification of a small groups of ataxias sharing similar imaging features. The integration of additional MRI findings, demographic, clinical and laboratory data allow then for the identification of typical, and in some cases pathognomonic, phenotypes of hereditary ataxias.

The impact of image contrast, resolution and reader expertise on black hole identification in Multiple Sclerosis.

OBJECTIVES: In the neuroradiological work-up of Multiple Sclerosis (MS), the detection of "black holes" (BH) represent an information of undeniable importance. Nevertheless, different sequences can be used in clinical practice to evaluate BH in MS. Aim of this study was to investigate the possible impact of different sequences, resolutions, and levels of expertise on the intra- and inter-rater reliability identification of BH in MS. METHODS: Brain MRI scans of 85 MS patients (M/F = 22/63; mean age = 36.0 ± 10.2 years) were evaluated in this prospective single-center study. The acquisition protocol included a 3 mm SE-T1w sequence, a 1 mm 3D-GrE-T1w sequence from which a resliced 3 mm sequence was also obtained. Images were evaluated independently by two readers of different expertise at baseline and after a wash-out period of 30 days. The intraclass correlation coefficient (ICC) was calculated as an index of intra and inter-reader reliability. RESULTS: For both readers, the intra-reader ICC analysis showed that the 3 mm SE-T1w and 3 mm resliced GrE-T1w images achieved an excellent performance (both with an ICC ≥ 0.95), while 1 mm 3D-GrE-T1w scans achieved a moderate one (ICC < 0.90). The inter-reader analysis showed that each of the three sequences achieved a moderate performance (all ICCs < 0.90). CONCLUSIONS: The 1 mm 3D-GrE-T1w sequence seems to be prone to a greater intra-reader variability compared to the 3 mm SE-T1w, with this effect being driven by the higher spatial resolution of the first sequence. To ensure reliability levels comparable with the standard SE-T1w in BH count, an assessment on a 3 mm resliced GrE-T1w sequence should be recommended.

In vivo demonstration of globotriaosylceramide brain accumulation in Fabry Disease using MR Relaxometry.

PURPOSE: How to measure brain globotriaosylceramide (Gb3) accumulation in Fabry Disease (FD) patients in-vivo is still an open challenge. The objective of this study is to provide a quantitative, non-invasive demonstration of this phenomenon using quantitative MRI (qMRI). METHODS: In this retrospective, monocentric cross-sectional study conducted from November 2015 to July 2018, FD patients and healthy controls (HC) underwent an MRI scan with a relaxometry protocol to compute longitudinal relaxation rate (R1) maps to evaluate gray (GM) and white matter (WM) lipid accumulation. In a subgroup of 22 FD patients, clinical (FAbry STabilization indEX -FASTEX- score) and biochemical (residual α-galactosidase activity) variables were correlated with MRI data. Quantitative maps were analyzed at both global ("bulk" analysis) and regional ("voxel-wise" analysis) levels. RESULTS: Data were obtained from 42 FD patients (mean age = 42.4 ± 12.9, M/F = 16/26) and 49 HC (mean age = 42.3 ± 16.3, M/F = 28/21). Compared to HC, FD patients showed a widespread increase in R1 values encompassing both GM (pFWE = 0.02) and WM (pFWE = 0.02) structures. While no correlations were found between increased R1 values and FASTEX score, a significant negative correlation emerged between residual enzymatic activity levels and R1 values in GM (r = -0.57, p = 0.008) and WM (r = -0.49, p = 0.03). CONCLUSIONS: We demonstrated the feasibility and clinical relevance of non-invasively assessing cerebral Gb3 accumulation in FD using MRI. R1 mapping might be used as an in-vivo quantitative neuroimaging biomarker in FD patients.

A rare case of De Garengeot hernia: CT findings.

We report a case of "De Garengeot's hernia" (DGH), a rare condition that occurs when the inflamed appendix is localized inside a femoral hernia. The appendix may be involved in inflammatory or necrotic processes and the treatment is emergency surgery. It is usually discovered by chance during surgery. It occurs in 0.5%-5% of all femoral hernias. In 0.08%-0.13% of cases, the appendix can present inflammatory or necrotic processes due to the narrowness of the neck of the femoral canal; in these cases, an emergency surgery is required through a no standard surgical procedure. In the other cases, it is usually found accidentally during surgical repair of the hernia or more rarely diagnosed preoperatively by CT. Therefore, the purpose of our study is to report a case of DGH describing CT main findings in order to improve the preoperative diagnosis.

StepBrain: A 3-Dimensionally Printed Multicompartmental Anthropomorphic Brain Phantom to Simulate PET Activity Distributions.

An innovative multicompartmental anatomic brain phantom (StepBrain) is described to simulate the in vivo tracer uptake of gray matter, white matter, and striatum, overcoming the limitations of currently available phantoms. Methods: StepBrain was created by exploiting the potential of fused deposition modeling 3-dimensional printing to replicate the real anatomy of the brain compartments, as modeled through ad hoc processing of healthy-volunteer MR images. Results: A realistic simulation of 18F-FDG PET brain studies, using target activity to obtain the real concentration ratios, was obtained, and the results of postprocessing with partial-volume effect correction tools developed for human PET studies confirmed the accuracy of these methods in recovering the target activity concentrations. Conclusion: StepBrain compartments (gray matter, white matter, and striatum) can be simultaneously filled, achieving different concentration ratios and allowing the simulation of different (e.g., amyloid, tau, or 6-fluoro-l-dopa) tracer distributions, with a potentially valuable role for multicenter PET harmonization studies.

Radiomics and artificial intelligence applications in pediatric brain tumors.

BACKGROUND: The study of central nervous system (CNS) tumors is particularly relevant in the pediatric population because of their relatively high frequency in this demographic and the significant impact on disease- and treatment-related morbidity and mortality. While both morphological and non-morphological magnetic resonance imaging techniques can give important information concerning tumor characterization, grading, and patient prognosis, increasing evidence in recent years has highlighted the need for personalized treatment and the development of quantitative imaging parameters that can predict the nature of the lesion and its possible evolution. For this purpose, radiomics and the use of artificial intelligence software, aimed at obtaining valuable data from images beyond mere visual observation, are gaining increasing importance. This brief review illustrates the current state of the art of this new imaging approach and its contributions to understanding CNS tumors in children. DATA SOURCES: We searched the PubMed, Scopus, and Web of Science databases using the following key search terms: ("radiomics" AND/OR "artificial intelligence") AND ("pediatric AND brain tumors"). Basic and clinical research literature related to the above key research terms, i.e., studies assessing the key factors, challenges, or problems of using radiomics and artificial intelligence in pediatric brain tumors management, was collected. RESULTS: A total of 63 articles were included. The included ones were published between 2008 and 2024. Central nervous tumors are crucial in pediatrics due to their high frequency and impact on disease and treatment. MRI serves as the cornerstone of neuroimaging, providing cellular, vascular, and functional information in addition to morphological features for brain malignancies. Radiomics can provide a quantitative approach to medical imaging analysis, aimed at increasing the information obtainable from the pixels/voxel grey-level values and their interrelationships. The "radiomic workflow" involves a series of iterative steps for reproducible and consistent extraction of imaging data. These steps include image acquisition for tumor segmentation, feature extraction, and feature selection. Finally, the selected features, via training predictive model (CNN), are used to test the final model. CONCLUSIONS: In the field of personalized medicine, the application of radiomics and artificial intelligence (AI) algorithms brings up new and significant possibilities. Neuroimaging yields enormous amounts of data that are significantly more than what can be gained from visual studies that radiologists can undertake on their own. Thus, new partnerships with other specialized experts, such as big data analysts and AI specialists, are desperately needed. We believe that radiomics and AI algorithms have the potential to move beyond their restricted use in research to clinical applications in the diagnosis, treatment, and follow-up of pediatric patients with brain tumors, despite the limitations set out.

Clinical and pathophysiological correlates of basilar artery measurements in Fabry Disease.

BACKGROUND AND PURPOSE: Alterations of the Basilar Artery (BA) anatomy have been suggested as a possible Magnetic Resonance Angiography (MRA) feature of Fabry Disease (FD). Nonetheless, no information about their clinical or pathophysiological correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD. MATERIALS AND METHODS: Brain MRIs of 53 FD subjects (40.7±12.4 years, M/F=23/30) were collected in this single center study. Mean BA diameter and its Tortuosity Index (TI) were calculated on MRA. Possible correlations between these metrics and clinical, laboratory and advanced imaging variables of the posterior circulation were tested. In a subgroup of 20 subjects, a two-year clinical and imaging follow-up was available, with possible longitudinal changes of these metrics and their ability in predicting clinical scores that were also probed. RESULTS: No significant association was found between MRA metrics and any clinical, laboratory or advanced imaging variable (ρ values ranging from -0.006 to 0.32). At the follow-up examination, no changes were observed over time for mean BA diameter (p = 0.84) and TI (p = 0.70). Finally, baseline MRA variables failed to predict the clinical status of FD patients at follow-up (p=0.42 and 0.66, respectively). CONCLUSIONS: Alterations of BA in FD lack of any significant association with clinical, laboratory or advanced imaging findings collected in this study. Furthermore, this lack of correlation seems constant over time, suggesting their stability over time. Taken together, all these results suggest that the role of BA dolichoectasia in FD should be reconsidered. ABBREVIATIONS: CNS = Central Nervous System; FASTEX = FAbry STabilization indEX; FD = Fabry Disease; Gb3 = Globotriaosylceramide; LysoGb3 = globotriaosylsphingosine; MSSI = Mainz Severity Score Index.

Gradient of microstructural damage along the dentato-thalamo-cortical tract in Friedreich ataxia.

OBJECTIVE: The dentato-thalamo-cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. METHODS: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross-sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. RESULTS: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. INTERPRETATION: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex.

Training radiology residents to evaluate deep myometrial invasion in endometrial cancer patients on MRI: A learning curve study.

PURPOSE: To evaluate the impact of a four-month training program on radiology residents' diagnostic accuracy in assessing deep myometrial invasion (DMI) in endometrial cancer (EC) using MRI. METHOD: Three radiology residents with limited EC MRI experience participated in the training program, which included conventional didactic sessions, case-centric workshops, and interactive classes. Utilizing a training dataset of 120 EC MRI scans, trainees independently assessed subsets of cases over five reading sessions. Each subset consisted of 30 scans, the first and the last with the same cases, for a total of 150 reads. Diagnostic accuracy metrics, assessment time (rounded to the nearest minute), and confidence levels (using a 5-point Likert scale) were recorded. The learning curve was obtained plotting the diagnostic accuracy of the three trainees and the average over the subsets. Anatomopathological results served as the reference standard for DMI presence. RESULTS: The three trainees exhibited heterogeneous starting point, with a learning curve and a trend to more homogeneous performance with training. The diagnostic accuracy of the average trainee raised from 64 % (56 %-76 %) to 88 % (80 %-94 %) across the five subsets (p < 0.001). Reductions in assessment time (5.92 to 4.63 min, p < 0.018) and enhanced confidence levels (3.58 to 3.97, p = 0.12) were observed. Improvements in sensitivity, specificity, positive predictive value, and negative predictive value were noted, particularly for specificity which raised from 56 % (41 %-68 %) in the first to 86 % (74 %-94 %) in the fifth subset (p = 0.16). Although not reaching statistical significance, these advancements aligned the trainees with literature performance benchmarks. CONCLUSIONS: The structured training program significantly enhanced radiology residents' diagnostic accuracy in assessing DMI for EC on MRI, emphasizing the effectiveness of active case-based training in refining oncologic imaging skills within radiology residency curricula.

Alzheimer's Disease and Small Vessel Disease Differentially Affect White Matter Microstructure.

OBJECTIVE: Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults. METHODS: Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid ß1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract. RESULTS: AD pathology, APOE-ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect. INTERPRETATION: Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.

Structural brain abnormalities and aggressive behaviour in schizophrenia: Mega-analysis of data from 2095 patients and 2861 healthy controls via the ENIGMA consortium.

Background: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. Methods: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. Results: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. Conclusions: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.