Despite the impact of psychiatric disorders on clinical health, early-stage diagnosis remains a challenge. Machine learning studies have shown that classifiers tend to be overly narrow in the diagnosis prediction task. The overlap between conditions leads to high heterogeneity among participants that is not adequately captured by classification models. To address this issue, normative approaches have surged as an alternative method. By using a generative model to learn the distribution of healthy brain data patterns, we can identify the presence of pathologies as deviations or outliers from the distribution learned by the model. In particular, deep generative models showed great results as normative models to identify neurological lesions in the brain. However, unlike most neurological lesions, psychiatric disorders present subtle changes widespread in several brain regions, making these alterations challenging to identify. In this work, we evaluate the performance of transformer-based normative models to detect subtle brain changes expressed in adolescents and young adults. We trained our model on 3D MRI scans of neurotypical individuals (N=1,765). Then, we obtained the likelihood of neurotypical controls and psychiatric patients with early-stage schizophrenia from an independent dataset (N=93) from the Human Connectome Project. Using the predicted likelihood of the scans as a proxy for a normative score, we obtained an AUROC of 0.82 when assessing the difference between controls and individuals with early-stage schizophrenia. Our approach surpassed recent normative methods based on brain age and Gaussian Process, showing the promising use of deep generative models to help in individualised analyses.

生成的对抗网络（GAN）是在众多领域成功使用的一种强大的深度学习模型。它们属于一个称为生成方法的更广泛的家族，该家族通过从真实示例中学习样本分布来生成新数据。在临床背景下，与传统的生成方法相比，GAN在捕获空间复杂，非线性和潜在微妙的疾病作用方面表现出增强的能力。这篇综述评估了有关gan在各种神经系统疾病的成像研究中的应用的现有文献，包括阿尔茨海默氏病，脑肿瘤，脑老化和多发性硬化症。我们为每个应用程序提供了各种GAN方法的直观解释，并进一步讨论了在神经影像学中利用gans的主要挑战，开放问题以及有希望的未来方向。我们旨在通过强调如何利用gan来支持临床决策，并有助于更好地理解脑部疾病的结构和功能模式，从而弥合先进的深度学习方法和神经病学研究之间的差距。

Normative modelling is an emerging method for understanding the underlying heterogeneity within brain disorders like Alzheimer Disease (AD) by quantifying how each patient deviates from the expected normative pattern that has been learned from a healthy control distribution. Since AD is a multifactorial disease with more than one biological pathways, multimodal magnetic resonance imaging (MRI) neuroimaging data can provide complementary information about the disease heterogeneity. However, existing deep learning based normative models on multimodal MRI data use unimodal autoencoders with a single encoder and decoder that may fail to capture the relationship between brain measurements extracted from different MRI modalities. In this work, we propose multi-modal variational autoencoder (mmVAE) based normative modelling framework that can capture the joint distribution between different modalities to identify abnormal brain structural patterns in AD. Our multi-modal framework takes as input Freesurfer processed brain region volumes from T1-weighted (cortical and subcortical) and T2-weighed (hippocampal) scans of cognitively normal participants to learn the morphological characteristics of the healthy brain. The estimated normative model is then applied on Alzheimer Disease (AD) patients to quantify the deviation in brain volumes and identify the abnormal brain structural patterns due to the effect of the different AD stages. Our experimental results show that modeling joint distribution between the multiple MRI modalities generates deviation maps that are more sensitive to disease staging within AD, have a better correlation with patient cognition and result in higher number of brain regions with statistically significant deviations compared to a unimodal baseline model with all modalities concatenated as a single input.

Over the years, Machine Learning models have been successfully employed on neuroimaging data for accurately predicting brain age. Deviations from the healthy brain aging pattern are associated to the accelerated brain aging and brain abnormalities. Hence, efficient and accurate diagnosis techniques are required for eliciting accurate brain age estimations. Several contributions have been reported in the past for this purpose, resorting to different data-driven modeling methods. Recently, deep neural networks (also referred to as deep learning) have become prevalent in manifold neuroimaging studies, including brain age estimation. In this review, we offer a comprehensive analysis of the literature related to the adoption of deep learning for brain age estimation with neuroimaging data. We detail and analyze different deep learning architectures used for this application, pausing at research works published to date quantitatively exploring their application. We also examine different brain age estimation frameworks, comparatively exposing their advantages and weaknesses. Finally, the review concludes with an outlook towards future directions that should be followed by prospective studies. The ultimate goal of this paper is to establish a common and informed reference for newcomers and experienced researchers willing to approach brain age estimation by using deep learning models

深层生成模型已成为检测数据中任意异常的有前途的工具，并分配了手动标记的必要性。最近，自回旋变压器在医学成像中取得了最先进的性能。但是，这些模型仍然具有一些内在的弱点，例如需要将图像建模为1D序列，在采样过程中误差的积累以及与变压器相关的显着推理时间。去核扩散概率模型是一类非自动回旋生成模型，最近显示出可以在计算机视觉中产生出色的样品（超过生成的对抗网络），并实现与变压器具有竞争力同时具有快速推理时间的对数可能性。扩散模型可以应用于自动编码器学到的潜在表示，使其易于扩展，并适用于高维数据（例如医学图像）的出色候选者。在这里，我们提出了一种基于扩散模型的方法，以检测和分段脑成像中的异常。通过在健康数据上训练模型，然后探索其在马尔可夫链上的扩散和反向步骤，我们可以识别潜在空间中的异常区域，因此可以确定像素空间中的异常情况。我们的扩散模型与一系列具有2D CT和MRI数据的实验相比，具有竞争性能，涉及合成和实际病理病变，推理时间大大减少，从而使它们的用法在临床上可行。

可以使用医学成像数据研究人类解剖学，形态和相关疾病。但是，访问医学成像数据受到治理和隐私问题，数据所有权和获取成本的限制，从而限制了我们理解人体的能力。解决此问题的一个可能解决方案是创建能够学习的模型，然后生成以相关性的特定特征（例如，年龄，性别和疾病状态）来生成人体的合成图像。最近，以神经网络形式的深层生成模型已被用于创建自然场景的合成2D图像。尽管如此，数据稀缺性，算法和计算局限性仍阻碍了具有正确解剖形态的高分辨率3D体积成像数据的能力。这项工作提出了一个生成模型，可以缩放以产生人类大脑的解剖学正确，高分辨率和现实的图像，并具有必要的质量，以允许进一步的下游分析。产生潜在无限数据的能力不仅能够对人体解剖学和病理学进行大规模研究，而不会危及患者的隐私，而且还可以在异常检测，模态综合，有限的数据和公平和公平和公平和公平和公平和公平和公平和公平和公平和公平和公平和公平和公平的学习领域进行显着提高。道德AI。代码和训练有素的模型可在以下网址提供：https：//github.com/amigolab/synthanatomy。

人脑解剖图像的专家解释是神经放射学的中心部分。已经提出了几种基于机器学习的技术来协助分析过程。但是，通常需要对ML模型进行培训以执行特定的任务，例如脑肿瘤分割或分类。相应的培训数据不仅需要费力的手动注释，而且人脑MRI中可以存在多种异常 - 甚至同时发生，这使得所有可能的异常情况都非常具有挑战性。因此，可能的解决方案是一种无监督的异常检测（UAD）系统，可以从健康受试者的未标记数据集中学习数据分布，然后应用以检测​​分布样本。然后，这种技术可用于检测异常 - 病变或异常，例如脑肿瘤，而无需明确训练该特定病理的模型。过去已经为此任务提出了几种基于变异的自动编码器（VAE）技术。即使它们在人为模拟的异常情况下表现良好，但其中许多在检测临床数据中的异常情况下表现较差。这项研究提出了“上下文编码” VAE（CEVAE）模型的紧凑版本，并结合了预处理和后处理步骤，创建了UAD管道（Strega）（Strega），该步骤对临床数据更强大，并显示其在检测到其检测方面的适用性脑MRI中的肿瘤等异常。 The proposed pipeline achieved a Dice score of 0.642$\pm$0.101 while detecting tumours in T2w images of the BraTS dataset and 0.859$\pm$0.112 while detecting artificially induced anomalies, while the best performing baseline achieved 0.522$\pm$0.135 and 0.783$\ PM分别为0.111美元。

Clinical diagnostic and treatment decisions rely upon the integration of patient-specific data with clinical reasoning. Cancer presents a unique context that influence treatment decisions, given its diverse forms of disease evolution. Biomedical imaging allows noninvasive assessment of disease based on visual evaluations leading to better clinical outcome prediction and therapeutic planning. Early methods of brain cancer characterization predominantly relied upon statistical modeling of neuroimaging data. Driven by the breakthroughs in computer vision, deep learning became the de facto standard in the domain of medical imaging. Integrated statistical and deep learning methods have recently emerged as a new direction in the automation of the medical practice unifying multi-disciplinary knowledge in medicine, statistics, and artificial intelligence. In this study, we critically review major statistical and deep learning models and their applications in brain imaging research with a focus on MRI-based brain tumor segmentation. The results do highlight that model-driven classical statistics and data-driven deep learning is a potent combination for developing automated systems in clinical oncology.

深度神经网络在医学图像分析中带来了显着突破。但是，由于其渴望数据的性质，医学成像项目中适度的数据集大小可能会阻碍其全部潜力。生成合成数据提供了一种有希望的替代方案，可以补充培训数据集并进行更大范围的医学图像研究。最近，扩散模型通过产生逼真的合成图像引起了计算机视觉社区的注意。在这项研究中，我们使用潜在扩散模型探索从高分辨率3D脑图像中生成合成图像。我们使用来自英国生物银行数据集的T1W MRI图像（n = 31,740）来训练我们的模型，以了解脑图像的概率分布，该脑图像以协变量为基础，例如年龄，性别和大脑结构量。我们发现我们的模型创建了现实的数据，并且可以使用条件变量有效地控制数据生成。除此之外，我们创建了一个带有100,000次脑图像的合成数据集，并使科学界公开使用。

临床实践中使用的医学图像是异质的，与学术研究中研究的扫描质量不同。在解剖学，伪影或成像参数不寻常或方案不同的极端情况下，预处理会分解。最需要对这些变化的方法可靠。提出了一种新颖的深度学习方法，以将人脑快速分割为132个区域。提出的模型使用有效的U-NET型网络，并从不同视图和分层关系的交点上受益，以在端到端训练期间融合正交2D平面和脑标签。部署了弱监督的学习，以利用部分标记的数据来进行整个大脑分割和颅内体积（ICV）的估计。此外，数据增强用于通过生成具有较高的脑扫描的磁共振成像（MRI）数据来扩展模型训练，同时保持数据隐私。提出的方法可以应用于脑MRI数据，包括头骨或任何其他工件，而无需预处理图像或性能下降。与最新的一些实验相比，使用了不同的Atlases的几项实验，以评估受过训练模型的分割性能，并且与不同内部和不同内部和不同内部方法的现有方法相比，结果显示了较高的分割精度和鲁棒性。间域数据集。

我们在自我神经调节任务中获得了一个人的学习进步的个人签名，由功能MRI（FMRI）为指导。签名基于在第一节中给定第二神经融合会话中Amygdala的活性。该预测由深神经网络进行，这是在整个培训队训练的患者的培训。该信号，其指示人在执行Amygdala调制任务方面的进步，在多个原型脑状态中聚集，然后通过线性分类器对各种个人和临床适应症进行分类。所获得的签名的预测力比以前从FMRI神经融合获得个人签名的方法更强，并且提供了人的学习模式可以用作诊断工具的指示。我们的代码已提供，并通过道德批准，共享数据。

背景：虽然卷积神经网络（CNN）实现了检测基于磁共振成像（MRI）扫描的阿尔茨海默病（AD）痴呆的高诊断准确性，但它们尚未应用于临床常规。这是一个重要原因是缺乏模型可理解性。最近开发的用于导出CNN相关性图的可视化方法可能有助于填补这种差距。我们调查了具有更高准确性的模型还依赖于先前知识预定义的判别脑区域。方法：我们培训了CNN，用于检测痴呆症和Amnestic认知障碍（MCI）患者的N = 663 T1加权MRI扫描的AD，并通过交叉验证和三个独立样本验证模型的准确性= 1655例。我们评估了相关评分和海马体积的关联，以验证这种方法的临床效用。为了提高模型可理解性，我们实现了3D CNN相关性图的交互式可视化。结果：跨三个独立数据集，组分离表现出广告痴呆症与控制的高精度（AUC $ \ GEQUQ $ 0.92）和MCI与控制的中等精度（AUC $ \约0.75美元）。相关性图表明海马萎缩被认为是广告检测的最具信息性因素，其其他皮质和皮质区域中的萎缩额外贡献。海马内的相关评分与海马体积高度相关（Pearson的r $ \大约$ -0.86，p <0.001）。结论：相关性地图突出了我们假设先验的地区的萎缩。这加强了CNN模型的可理解性，这些模型基于扫描和诊断标签以纯粹的数据驱动方式培训。

近年来，来自神经影像数据的脑疾病的单一受试者预测引起了人们的关注。然而，对于某些异质性疾病，例如严重抑郁症（MDD）和自闭症谱系障碍（ASD），大规模多站点数据集对预测模型的性能仍然很差。我们提出了一个两阶段的框架，以改善静止状态功能磁共振成像（RS-FMRI）的异质精神疾病的诊断。首先，我们建议对健康个体的数据进行自我监督的掩盖预测任务，以利用临床数据集中健康对照与患者之间的差异。接下来，我们在学习的判别性表示方面培训了一个有监督的分类器。为了建模RS-FMRI数据，我们开发Graph-S4；最近提出的状态空间模型S4扩展到图形设置，其中底层图结构未提前知道。我们表明，将框架和Graph-S4结合起来可以显着提高基于神经成像的MDD和ASD的基于神经影像学的单个主题预测模型和三个开源多中心RS-FMRI临床数据集的诊断性能。

Anomaly detection in MRI is of high clinical value in imaging and diagnosis. Unsupervised methods for anomaly detection provide interesting formulations based on reconstruction or latent embedding, offering a way to observe properties related to factorization. We study four existing modeling methods, and report our empirical observations using simple data science tools, to seek outcomes from the perspective of factorization as it would be most relevant to the task of unsupervised anomaly detection, considering the case of brain structural MRI. Our study indicates that anomaly detection algorithms that exhibit factorization related properties are well capacitated with delineatory capabilities to distinguish between normal and anomaly data. We have validated our observations in multiple anomaly and normal datasets.

主要的神经影像学研究推动了1.0 mm以下的3T MRI采集分辨率，以改善结构定义和形态学。然而，只有很少的时间 - 密集的自动化图像分析管道已被验证为高分辨率（雇用）设置。另一方面，有效的深度学习方法很少支持多个固定分辨率（通常1.0 mm）。此外，缺乏标准的杂交数据分辨率以及具有足够覆盖的扫描仪，年龄，疾病或遗传方差的多样化数据的有限可用性会带来额外的，未解决的挑战培训网络。将分辨率独立于基于深度学习的分割，即在一系列不同的体素大小上以其本地分辨率进行分辨率的能力，承诺克服这些挑战，但目前没有这种方法。我们现在通过向决议独立的分割任务（VINN）引入VINOSEIZED独立的神经网络（VINN）来填补这个差距，并呈现FastSurfervinn，（i）建立并实施决议独立，以获得深度学习作为同时支持0.7-1.0 mm的第一种方法分割，（ii）显着优于跨决议的最先进方法，（iii）减轻雇用数据集中存在的数据不平衡问题。总体而言，内部分辨率 - 独立性相互益处雇用和1.0 mm MRI分割。通过我们严格验证的FastSurfervinn，我们将为不同的神经视线镜分析分发一个快速工具。此外，VINN架构表示更广泛应用的有效分辨率的分段方法

我们介绍了用于分析功能磁共振成像（FMRI）数据的TFF变压器框架。TFF采用基于变压器的架构和两阶段培训方法。首先，自我监督培训适用于FMRI扫描的集合，其中模型培训用于重建3D卷数据。其次，预训练模型在特定任务上进行了微调，利用地面真理标签。我们的结果显示了各种FMRI任务的最先进的性能，包括年龄和性别预测，以及精神分裂症认可。

机器学习方法利用多参数生物标志物，特别是基于神经影像动物，具有改善痴呆早期诊断的巨大潜力，并预测哪些个体存在发展痴呆的风险。对于机器学习领域的基准算法和痴呆症中的神经影像症，并评估他们在临床实践中使用的潜力和临床试验，七年的大挑战已经在过去十年中组织：Miriad，Alzheimer的疾病大数据梦，Caddementia，机器学习挑战，MCI神经影像动物，蝌蚪和预测分析竞争。基于两个挑战评估框架，我们分析了这些大挑战如何互相补充研究问题，数据集，验证方法，结果和影响。七个大挑战解决了与（临床前）痴呆症（临床）痴呆症的筛查，诊断，预测和监测有关的问题。临床问题，任务和性能指标几乎没有重叠。然而，这具有提供对广泛问题的洞察力的优势，它也会限制对挑战的结果的验证。通常，获胜算法执行严格的数据预处理并组合了广泛的输入特征。尽管最先进的表演，但临床上没有挑战评估的大部分方法。为了增加影响，未来的挑战可以更加关注统计分析，对其与高于阿尔茨海默病的临床问题，以及使用超越阿尔茨海默病神经影像疾病的临床问题，以及超越阿尔茨海默病的临床问题。鉴于过去十年中汲取的潜力和经验教训，我们在未来十年及其超越的机器学习和神经影像中的大挑战前景兴奋。

Pooling publicly-available MRI data from multiple sites allows to assemble extensive groups of subjects, increase statistical power, and promote data reuse with machine learning techniques. The harmonization of multicenter data is necessary to reduce the confounding effect associated with non-biological sources of variability in the data. However, when applied to the entire dataset before machine learning, the harmonization leads to data leakage, because information outside the training set may affect model building, and potentially falsely overestimate performance. We propose a 1) measurement of the efficacy of data harmonization; 2) harmonizer transformer, i.e., an implementation of the ComBat harmonization allowing its encapsulation among the preprocessing steps of a machine learning pipeline, avoiding data leakage. We tested these tools using brain T1-weighted MRI data from 1740 healthy subjects acquired at 36 sites. After harmonization, the site effect was removed or reduced, and we measured the data leakage effect in predicting individual age from MRI data, highlighting that introducing the harmonizer transformer into a machine learning pipeline allows for avoiding data leakage.

The primary goal of this work is to study the effectiveness of an unsupervised domain adaptation approach for various applications such as binary classification and anomaly detection in the context of Alzheimer's disease (AD) detection for the OASIS datasets. We also explore image reconstruction and image synthesis for analyzing and generating 3D structural MRI data to establish performance benchmarks for anomaly detection. We successfully demonstrate that domain adaptation improves the performance of AD detection when implemented in both supervised and unsupervised settings. Additionally, the proposed methodology achieves state-of-the-art performance for binary classification on the OASIS-1 dataset.

Many clinical and research studies of the human brain require an accurate structural MRI segmentation. While traditional atlas-based methods can be applied to volumes from any acquisition site, recent deep learning algorithms ensure very high accuracy only when tested on data from the same sites exploited in training (i.e., internal data). The performance degradation experienced on external data (i.e., unseen volumes from unseen sites) is due to the inter-site variabilities in intensity distributions induced by different MR scanner models, acquisition parameters, and unique artefacts. To mitigate this site-dependency, often referred to as the scanner effect, we propose LOD-Brain, a 3D convolutional neural network with progressive levels-of-detail (LOD) able to segment brain data from any site. Coarser network levels are responsible to learn a robust anatomical prior useful for identifying brain structures and their locations, while finer levels refine the model to handle site-specific intensity distributions and anatomical variations. We ensure robustness across sites by training the model on an unprecedented rich dataset aggregating data from open repositories: almost 27,000 T1w volumes from around 160 acquisition sites, at 1.5 - 3T, from a population spanning from 8 to 90 years old. Extensive tests demonstrate that LOD-Brain produces state-of-the-art results, with no significant difference in performance between internal and external sites, and robust to challenging anatomical variations. Its portability opens the way for large scale application across different healthcare institutions, patient populations, and imaging technology manufacturers. Code, model, and demo are available at the project website.