Contrast Enhancing Pattern on Pre-Treatment MRI predicts Response to Anti-Angiogenic Treatment in Recurrent Glioblastoma: Comparison of Bevacizumab and Temozolomide Treatment

Objective: To evaluate the value of the contrast enhancing pattern on pre-treatment MRI for predicting the response to anti-angiogenic treatment in patients with IDH-wild type recurrent glioblastoma.Methods: This retrospective study enrolled 65 patients with IDH wild-type recurrent glioblastoma who received standard therapy and then received either bevacizumab (46 patients) or temozolomide (19 patients) as a secondary treatment. The contrast enhancing pattern on pre-treatment MRI was visually analyzed and dichotomized into contrast enhancing lesion (CEL) dominant and non-enhancing lesion (NEL) dominant types. Quantitative volumetric analysis was used to support the dichotomization. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to stratify progression free survival (PFS) according to the treatment in the entire patients, CEL dominant group, and NEL dominant group.Results: In all patients, the PFS of those treated with bevacizumab was not significantly different from those treated with temozolomide (log-rank test, P=.96). When the contrast enhancing pattern was considered, bevacizumab was associated with longer PFS in the CEL dominant group (P=.031), whereas temozolomide showed longer PFS in the NEL dominant group (P=.022). Quantitative analysis revealed cut-offs for the proportion of solid-enhancing tumor of 13.7% for the CEL dominant group and 4.3% for the NEL dominant group. Conclusions: Patients with the CEL dominant type showed a better treatment response to bevacizumab, whereas NEL dominant types showed a better response to temozolomide. The contrast enhancing pattern on pre-treatment MRI can be used to stratify patients with IDH wild-type recurrent glioblastoma according to the effect of anti-angiogenic treatment.

Volumetric comparative analysis of anatomy through far-lateral approach: surgical space and exposed tissues

Background The three-dimensional (3D) visualization model has ability to quantify the surgical anatomy of far-lateral approach. This study was designed to disclose the relationship between surgical space and exposed tissues in the far-lateral approach by the volumetric analysis of 3D model. Methods The 3D skull base models were constructed using MRI and CT data of 15 patients (30 sides) with trigeminal neuralgia. Surgical corridors of the far-lateral approach were simulated by triangular pyramids to represent two surgical spaces exposing bony and neurovascular tissues. Volumetric comparison of surgical anatomy was performed using pair t test. Results The morphometric results were almost the same in the two surgical spaces except the vagus nerve (CN X) exposed only in one corridor, whereas the volumetric comparison represented the statistical significant differences of surgical space and bony and neurovascular tissues involved in the two corridors (P<0.001). The differences of bony and neurovascular tissues failed to equal the difference of surgical space. Conclusions For far-lateral approach, the increase of exposure for the bony and neurovascular tissues is not necessarily matched with the increase of surgical space. The volumetric comparative analysis is helpful to provide more detailed anatomical information in the surgical design.

CBCT in dental age estimation: A systematic review and meta analysis

Objectives: This study aimed to investigate the reproducibility of dental age estimation methods in cone beam computed tomography (CBCT) and the correlation between dental (DA) and chronological (CA) ages. Methods: The scientific literature was searched in six databases (PubMed, Scopus, LILACS, Web of Science, SciELO, and OATD). Only observational studies were selected. Within each study, the outcomes of interest were (I) the quantified reproducibility of the method (κ statistics and Intraclass correlation coefficient); and (II) the correlation (r) between the dental and chronological ages. A random-effect three-level meta-analysis was conducted alongside moderator analysis based on methods, arch (maxillary/mandibular), population, and number of roots. Results: From 671 studies, 39 fulfilled the inclusion criteria, with one study reporting two different methods. The methods used in the studies were divided into metric (n = 17), volumetric (n = 20), staging (n = 2), and atlas (n = 1). All studies reported high examiner reproducibility. Group 1 (metric and volumetric) provided a high inverse weighted r ([Formula: see text] = −0.71, CI [-0.79,–0.61]), and Group 2 (staging) provided a medium-weighted r ([Formula: see text] = 0.49, CI [0.44, 0.53]). Moderator analysis on Group one did not show statistically significant differences between methods, tooth position, arch, and number of roots. An exception was detected in the analysis based on population (Southeast Asia, [Formula: see text] = −0.89, CI [-0.94,–0.81]). Conclusion: There is high evidence that CBCT methods are reproducible and reliable in dental age estimation. Quantitative metric and volumetric analysis demonstrated better performance in predicting chronological age than staging. Future studies exploring population-specific variability for age estimation with metric and volumetric CBCT analysis may prove beneficial.

Concomitant AD and DLB pathologies shape subfield microglia responses in the hippocampus

Hippocampal alteration is at the centre of memory decline in the most common age-related neurodegenerative diseases: Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB). However, the subregional deterioration of the hippocampus differs between both diseases with more severe atrophy in the CA1 subfield of the AD patients. How AD and DLB-typical pathologies compose the various local microenvironment of the hippocampus across AD and DLB needs to be further explored to understand this process. Additionally, microglia responses could further impact the atrophy rate. Some studies suggest that microglia react differently according to the underlying neurodegenerative disorder. How microglia are transformed across hippocampal subfields in AD and DLB, and how their changes are associated with disease-typical pathologies remains to be determined. To these purposes, we performed a volumetric analysis of phospho-Tau (P-Tau), Amyloid-beta (Abeta), and phospho-alpha-Synuclein (P-Syn) loads, quantified and classified microglia according to distinct morphological phenotypes using high-resolution confocal 3D microscopy of hippocampal CA1, CA3 and DG/CA4 subfields of late-onset AD (n=10) and DLB (n=8) as well as age-matched control samples (n=11). We found that each of the Tau, Abeta and Synuclein pathologies followed a specific subregional distribution, relatively preserved across AD and DLB. P-Tau, Abeta and P-Syn burdens were significantly exacerbated in AD, with Tau pathology being particularly severe in the AD CA1. P-Tau and P-Syn burdens were highly correlated across subfields and conditions (R2Spear = 0.79; P < 0.001) and result from a local co-distribution of P-Tau and P-Syn inclusions in neighbouring neurons, with only a low proportion of double-positive cells. In parallel, we assessed the changes of the microglia responses by measuring 16 morphological features of more than 35,000 individual microglial cells and classifying them into seven-distinct morphological clusters. We found microglia features- and clusters-variations subfield- and condition-dependent. Two of the seven morphological clusters, with more amoeboid and less branched forms, were identified as disease-enriched and found to be further increased in AD. Interestingly, some microglial features or clusters were associated with one but more often with a combination of two pathologies in a subfield-dependent manner. In conclusion, our study shows a multimodal association of the hippocampal microglia responses with the co-occurrence, distribution and severity of AD and DLB pathologies. In DLB hippocampi, pathological imprint and microglia responses follow AD trends but with lesser severity. Our study suggests that the increased pathological burdens of P-Tau and P-Syn and associated microglia alterations are involved in a more severe deterioration of the CA1 in AD as compared to DLB.

TorchEsegeta: Framework for Interpretability and Explainability of Image-based Deep Learning Models

Clinicians are often very sceptical about applying automatic image processing approaches, especially deep learning based methods, in practice. One main reason for this is the black-box nature of these approaches and the inherent problem of missing insights of the automatically derived decisions. In order to increase trust in these methods, this paper presents approaches that help to interpret and explain the results of deep learning algorithms by depicting the anatomical areas which influence the decision of the algorithm most. Moreover, this research presents a unified framework, TorchEsegeta, for applying various interpretability and explainability techniques for deep learning models and generate visual interpretations and explanations for clinicians to corroborate their clinical findings. In addition, this will aid in gaining confidence in such methods. The framework builds on existing interpretability and explainability techniques that are currently focusing on classification models, extending them to segmentation tasks. In addition, these methods have been adapted to 3D models for volumetric analysis. The proposed framework provides methods to quantitatively compare visual explanations using infidelity and sensitivity metrics. This framework can be used by data scientists to perform post-hoc interpretations and explanations of their models, develop more explainable tools and present the findings to clinicians to increase their faith in such models. The proposed framework was evaluated based on a use case scenario of vessel segmentation models trained on Time-of-fight (TOF) Magnetic Resonance Angiogram (MRA) images of the human brain. Quantitative and qualitative results of a comparative study of different models and interpretability methods are presented. Furthermore, this paper provides an extensive overview of several existing interpretability and explainability methods.

MRI Volumetric Analysis of the Thalamus and Hypothalamus in Amyotrophic Lateral Sclerosis

Background: Increasing evidence has shown that amyotrophic lateral sclerosis (ALS) can result in abnormal energy metabolism and sleep disorders, even before motor dysfunction. Although the hypothalamus and thalamus are important structures in these processes, few ALS studies have reported abnormal MRI structural findings in the hypothalamus and thalamus.Purpose: We aimed to investigate volumetric changes in the thalamus and hypothalamus by using the automatic brain structure volumetry tool AccuBrain®.Methods: 3D T1-weighted magnetization-prepared gradient echo imaging (MPRAGE) scans were acquired from 16 patients with ALS with normal cognitive scores and 16 age-, sex- and education-matched healthy controls. Brain tissue and structure volumes were automatically calculated using AccuBrain®.Results: There were no significant differences in bilateral thalamic (F = 1.31, p = 0.287) or hypothalamic volumes (F = 1.65, p = 0.213) between the ALS and control groups by multivariate analysis of covariance (MANCOVA). Left and right hypothalamic volumes were correlated with whole-brain volume in patients with ALS (t = 3.19, p = 0.036; t = 3.03, p = 0.044), while the correlation between age and bilateral thalamic volumes tended to be significant after Bonferroni correction (t = 2.76, p = 0.068; t = 2.83, p = 0.06). In the control group, left and right thalamic volumes were correlated with whole-brain volume (t = 4.26, p = 0.004; t = 4.52, p = 0.004).Conclusion: Thalamic and hypothalamic volumes did not show differences between patients with normal frontotemporal function ALS and healthy controls, but further studies are still needed.

Neural Correlates of Letter and Semantic Fluency in Primary Progressive Aphasia

Verbal fluency (VF) is an informative cognitive task. Lesion and functional imaging studies implicate distinct cerebral areas that support letter versus semantic fluency and the understanding of neural and cognitive mechanisms underlying task performance. Most lesion studies include chronic stroke patients. People with primary progressive aphasia (PPA) provide complementary evidence for lesion-deficit associations, as different brain areas are affected in stroke versus PPA. In the present study we sought to determine imaging, clinical and demographic correlates of VF in PPA. Thirty-five patients with PPA underwent an assessment with letter and category VF tasks, evaluation of clinical features and an MRI scan for volumetric analysis. We used stepwise regression models to determine which brain areas are associated with VF performance while acknowledging the independent contribution of clinical and demographic factors. Letter fluency was predominantly associated with language severity (R2 = 38%), and correlated with the volume of the left superior temporal regions (R2 = 12%) and the right dorsolateral prefrontal area (R2 = 5%). Semantic fluency was predominantly associated with dementia severity (R2 = 47%) and correlated with the volume of the left inferior temporal gyrus (R2 = 7%). No other variables were significantly associated with performance in the two VF tasks. We concluded that, independently of disease severity, letter fluency is significantly associated with the volume of frontal and temporal areas whereas semantic fluency is associated mainly with the volume of temporal areas. Furthermore, our findings indicated that clinical severity plays a critical role in explaining VF performance in PPA, compared to the other clinical and demographic factors.

Histopathological Investigation of Dura-Like Membrane in Vestibular Schwannomas

The dura-like membrane (DLM) is an outermost membranous structure arising from the dura mater adjacent to the internal auditory meatus (IAM) that envelops some vestibular schwannomas (VSs). Its recognition is important for the preservation of the facial and cochlear nerves during tumor resection. This study analyzes the histopathological characteristics of the DLM. The expression of CD34 and αSMA was histopathologically analyzed in tumor and DLM tissue of 10 primary VSs with and without a DLM. Tumor volume, resection volume percentage, microvessel density (MVD), and vessel diameter were analyzed. Volumetric analysis revealed that the presence of a DLM was significantly associated with lower tumor resection volume (p < 0.05). Intratumoral vessel diameter was significantly larger in the DLM group than the non-DLM group (p < 0.01). Larger VSs showed a higher intratumoral MVD in the DLM group (p < 0.05). Multilayered αSMA-positive vessels were identified in the DLM, tumor, and border; there tended to be more of these vessels within the tumor in the DLM group compared to the non-DLM group (p = 0.08). These arteriogenic characteristics suggest that the DLM is formed as the tumor induces feeding vessels from the dura mater around the IAM.

HAVAs: Alzheimer’s Disease Detection using Normative and Pathological Lifespan Models

In this paper, we present an innovative MRI-based method for Alzheimer’s Disease (AD) detection and mild cognitive impairment (MCI) prognostic, using lifespan trajectories of brain structures. After a full screening of the most discriminant structures between AD and normal aging based on MRI volumetric analysis of 3032 subjects, we propose a novel Hippocampal-Amygdalo-Ventricular Alzheimer score (HAVAs) based on normative lifespan models and AD lifespan models. During a validation on three external datasets on 1039 subjects, our approach showed very accurate detection (AUC ≥ 94%) of patients with AD compared to control subjects and accurate discrimination (AUC=78%) between progressive MCI and stable MCI (during a 3 years follow-up). Compared to normative modelling and recent state-of-the-art deep learning methods, our method demonstrated better classification performance. Moreover, HAVAs simplicity makes it fully understandable and thus well-suited for clinical practice or future pharmaceutical trials.