This paper presents a new method for medical diagnosis of neurodegenerative diseases, such as Parkinson's, by extracting and using latent information from trained Deep convolutional, or convolutional-recurrent Neural Networks (DNNs). In particular, our approach adopts a combination of transfer learning, k-means clustering and k-Nearest Neighbour classification of deep neural network learned representations to provide enriched prediction of the disease based on MRI and or DaT Scan data. A new loss function is introduced and used in the training of the DNNs, so as to perform adaptation of the generated learned representations between data from different medical environments. Results are presented using a recently published database of Parkinson's related information, which was generated and evaluated in a hospital environment.
A Parkinson's database comprising MRI and DaT Scan data from 78 subjects, 55 patients with Parkinson's and 23 non patients, has been recently released @cite_14 ; it includes, in total 41528 MRI data (31147 from patients and 10381 from non patients) and 925 DaT scans (595 and 330 respectively). Our developments next are based on this database.
@cite_14
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Availability of multi-modal magnetic resonance imaging (MRI) databases opens up the opportunity to synthesize different MRI contrasts without actually acquiring the images. In theory such synthetic images have the potential to reduce the amount of acquisitions to perform certain analyses. However, to what extent they can substitute real acquisitions in the respective analyses is an open question. In this study, we used a synthesis method based on patch matching to test whether synthetic images can be useful in segmentation and inter-modality cross-subject registration of brain MRI. Thirty-nine T1 scans with 36 manually labeled structures of interest were used in the registration and segmentation of eight proton density (PD) scans, for which ground truth T1 data were also available. The results show that synthesized T1 contrast can considerably enhance the quality of non-linear registration compared with using the original PD data, and it is only marginally worse than using the original T1 scans. In segmentation, the relative improvement with respect to using the PD is smaller, but still statistically significant. Automatic extraction of features from MRI brain scans and diagnosis of Alzheimer's Disease (AD) remain a challenging task. In this paper, we propose an efficient and simple three-dimensional convolutional network (3D ConvNet) architecture that is able to achieve high performance for detection of AD on a relatively large dataset. The proposed 3D ConvNet consists of five convolutional layers for feature extraction, followed by three fully-connected layers for AD NC classification. The main contributions of the paper include: (a) propose a novel and effective 3D ConvNet architecture; (b) study the impact of hyper-parameter selection on the performance of AD classification; (c) study the impact of pre-processing; (d) study the impact of data partitioning; (e) study the impact of dataset size. Experiments conducted on an ADNI dataset containing 340 subjects and 1198 MRI brain scans have resulted good performance (with the test accuracy of 98.74 , 100 AD detection rate and 2,4 false alarm). Comparisons with 7 existing state-of-the-art methods have provided strong support to the robustness of the proposed method. Background Individual magnetic resonance imaging (MRI) disease severity measures, such as atrophy or lesions, show weak relationships to clinical status in patients with multiple sclerosis (MS). Objective To combine MS-MRI measures of disease severity into a composite score. Design Retrospective analysis of prospectively collected data. Setting Community-based and referral subspecialty clinic in an academic hospital. Patients A total of 103 patients with MS, with a mean (SD) Expanded Disability Status Scale (EDSS) score of 3.3 (2.2), of whom 62 (60.2 ) had the relapsing-remitting, 33 (32.0 ) the secondary progressive, and 8 (7.8 ) the primary progressive form. Main Outcome Measures Brain MRI measures included baseline T2 hyperintense (T2LV) and T1 hypointense (T1LV) lesion volume and brain parenchymal fraction (BPF), a marker of global atrophy. The ratio of T1LV to T2LV (T1:T2) assessed lesion severity. A Magnetic Resonance Disease Severity Scale (MRDSS) score, on a continuous scale from 0 to 10, was derived for each patient using T2LV, BPF, and T1:T2. Results The MRDSS score averaged 5.1 (SD, 2.6). Baseline MRI and EDSS correlations were moderate for BPF, T1:T2, and MRDSS and weak for T2LV. The MRDSS showed a larger effect size than the individual MRI components in distinguishing patients with the relapsing-remitting form from those with the secondary progressive form. Models containing either T2LV or MRDSS were significantly associated with disability progression during the mean (SD) 3.2 (0.3)–year observation period, when adjusting for baseline EDSS score. Conclusion Combining brain MRI lesion and atrophy measures can predict MS clinical progression and provides the basis for developing an MRI-based continuous scale as a marker of MS disease severity. Objective: We describe the sampling, initial evaluation, and final diagnostic classification of subjects enrolled in a natural history study of Alzheimer's disease (AD). Design: Volunteer cohort study. Setting: Multidisciplinary behavioral neurology research clinic. Patients or Other Participants: Three-hundred nineteen individuals were enrolled in the Alzheimer Research Program between March 1983 and March 1988. Of these, 204 were originally classified with AD, 102 were normal elderly control subjects, and 13 were considered special cases. Main Outcome Measures: Final consensus clinical diagnosis, final neuropathologic diagnosis, and death. Results: Of the 204 patients enrolled in the study, re-review after as many as 5 years of follow-up resulted in a final clinical classification of 188 with probable AD. Seven patients were believed to have a significant vascular component to the dementia, three were found to have developed depression, and six were excluded on other clinical grounds. Neuropathologic examination of 50 brains indicated definite AD in 43. After removing these seven misdiagnosed patients, the final group of probable definite AD totaled 181 individuals. Accuracy of the baseline clinical diagnosis relative to neuropathology was 86 , and when follow-up clinical data were considered, 91.4 . Detailed neuropsychological testingyielded high sensitivity (0.988) and specificity (0.983) to dementia. Analyses of survival time from study entry until death revealed that older patients were significantly more likely to die during follow-up, but neither sex, years of education, nor pattern of cognitive impairment were related to survival. Conclusions: These data provide the descriptive basis for future studies of this cohort. They indicate that longitudinal follow-up of demented cases increases accuracy of diagnosis, and that detailed cognitive testing aids in early classification. We describe a new method to automatically discriminate between patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and elderly controls, based on multidimensional classification of hippocampal shape features. This approach uses spherical harmonics (SPHARM) coefficients to model the shape of the hippocampi, which are segmented from magnetic resonance images (MRI) using a fully automatic method that we previously developed. SPHARM coefficients are used as features in a classification procedure based on support vector machines (SVM). The most relevant features for classification are selected using a bagging strategy. We evaluate the accuracy of our method in a group of 23 patients with AD (10 males, 13 females, age+ -standard-deviation (SD)=73+ -6 years, mini-mental score (MMS)=24.4+ -2.8), 23 patients with amnestic MCI (10 males, 13 females, age+ -SD=74+ -8 years, MMS=27.3+ -1.4) and 25 elderly healthy controls (13 males, 12 females, age+ -SD=64+ -8 years), using leave-one-out cross-validation. For AD vs controls, we obtain a correct classification rate of 94 , a sensitivity of 96 , and a specificity of 92 . For MCI vs controls, we obtain a classification rate of 83 , a sensitivity of 83 , and a specificity of 84 . This accuracy is superior to that of hippocampal volumetry and is comparable to recently published SVM-based whole-brain classification methods, which relied on a different strategy. This new method may become a useful tool to assist in the diagnosis of Alzheimer's disease. Mobile phones with built-in accelerometers promise a convenient, objective way to quantify everyday movements and classify those movements into activities. Using accelerometer data we estimate the activities of 18 healthy subjects and 8 patients with Parkinson’s disease – e.g. walking, standing, sitting, or simply holding the phone. We use standard machine learning classifiers (support vector machines, regularized logistic regression) to automatically select, weigh, and combine a large set of standard features for time series analysis. Using crossvalidation across all samples we are able to correctly identify 96.1 of the activities of healthy subjects and 92.2 of the activities of Parkinson’s patients. However, when applying the classification parameters derived from the set of healthy subjects to Parkinson’s patients, the percent correct lowers to 60.3 , due to different characteristics of movement. For a fairer comparison across populations we also applied subject-wise crossvalidation, identifying healthy subject activities with 86.0 accuracy and 75.1 accuracy for patients. We discuss the key differences between these populations, and why algorithms designed for and trained with healthy subject data are not reliable for activity recognition in populations with motor disabilities. BACKGROUND: Alzheimer's disease (AD) patients show early changes in white matter (WM) structural integrity. We studied the use of diffusion tensor imaging (DTI) in assessing WM alterations in the predementia stage of mild cognitive impairment (MCI). METHODS: We applied a Support Vector Machine (SVM) classifier to DTI and volumetric magnetic resonance imaging data from 35 amyloid-β42 negative MCI subjects (MCI-Aβ42-), 35 positive MCI subjects (MCI-Aβ42+), and 25 healthy controls (HC) retrieved from the European DTI Study on Dementia. The SVM was applied to DTI-derived fractional anisotropy, mean diffusivity (MD), and mode of anisotropy (MO) maps. For comparison, we studied classification based on gray matter (GM) and WM volume. RESULTS: We obtained accuracies of up to 68 for MO and 63 for GM volume when it came to distinguishing between MCI-Aβ42- and MCI-Aβ42+. When it came to separating MCI-Aβ42+ from HC we achieved an accuracy of up to 77 for MD and a significantly lower accuracy of 68 for GM volume. The accuracy of multimodal classification was not higher than the accuracy of the best single modality. CONCLUSIONS: Our results suggest that DTI data provide better prediction accuracy than GM volume in predementia AD. Abstract Brain extraction from magnetic resonance imaging (MRI) is crucial for many neuroimaging workflows. Current methods demonstrate good results on non-enhanced T1-weighted images, but struggle when confronted with other modalities and pathologically altered tissue. In this paper we present a 3D convolutional deep learning architecture to address these shortcomings. In contrast to existing methods, we are not limited to non-enhanced T1w images. When trained appropriately, our approach handles an arbitrary number of modalities including contrast-enhanced scans. Its applicability to MRI data, comprising four channels: non-enhanced and contrast-enhanced T1w, T2w and FLAIR contrasts, is demonstrated on a challenging clinical data set containing brain tumors (N = 53), where our approach significantly outperforms six commonly used tools with a mean Dice score of 95.19. Further, the proposed method at least matches state-of-the-art performance as demonstrated on three publicly available data sets: IBSR, LPBA40 and OASIS, totaling N = 135 volumes. For the IBSR (96.32) and LPBA40 (96.96) data set the convolutional neuronal network (CNN) obtains the highest average Dice scores, albeit not being significantly different from the second best performing method. For the OASIS data the second best Dice (95.02) results are achieved, with no statistical difference in comparison to the best performing tool. For all data sets the highest average specificity measures are evaluated, whereas the sensitivity displays about average results. Adjusting the cut-off threshold for generating the binary masks from the CNN's probability output can be used to increase the sensitivity of the method. Of course, this comes at the cost of a decreased specificity and has to be decided application specific. Using an optimized GPU implementation predictions can be achieved in less than one minute. The proposed method may prove useful for large-scale studies and clinical trials. Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n=30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0 and an area under the receiver-operating-characteristic curve (AUC) of 78.8 . In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http: caddementia.grand-challenge.org. This paper analyses gait patterns of patients with Parkinson;s Disease (PD) based on the acceleration data given by an e-AR sensor. Ten PD patients wearing the e-AR sensor walked along a 7m walkway and each session contained 16 repeated trials. An iterative algorithm has been proposed to produce robust estimations in the case of measurement noise and short-duration of gait signals. Step-frequency as a gait parameter derived from the estimated heel-contacts is calculated and validated using the CODA motion-capture system. Intersession variability of step-frequency for each patient and the overall variability across patients demonstrate a good agreement between estimations from the e-AR and CODA systems. Using multivariate analyses, individual risk of clinically definite multiple sclerosis (C DMS) after monosymptomatic optic neuritis (MO N) was quantified in a prospective study with clinical MO N onset during 1990 -95 in Stockholm, Sweden. During a mean follow-up time of 3.8 years, the presence of MS-like brain magnetic resonance imaging (MRI) lesions and oligoclonal immunoglobulin (Ig) G bands in cerebrospinal fluid (CSF) were strong prognostic markers of C DMS, with relative hazard ratios of 4.68 95 confidence interval (CI) 2.21 -9.91 and 5.39 (95 C I 1.56 -18.61), respectively. Age and season of clinical onset were also significant predictors, with relative hazard ratios of 1.76 (95 C I 1.02 -3.04) and 2.21 (95 C I 1.13 -3.98), respectively. Based on the above two strong predicto rs, individual probability of C DMS development after MO N was calculated in a three-quarter sample drawn from a cohort, with completion of follow-up at three years. The highest probability, 0.66 (95 C I 0.48 -0.80), wa... Alzheimer’s disease (AD) is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects. Abstract We propose a new method of measuring atrophy of brain structures by simultaneously segmenting longitudinal magnetic resonance (MR) images. In this approach a 4D graph is used to represent the longitudinal data: edges are weighted based on spatial and intensity priors and connect spatially and temporally neighboring voxels represented by vertices in the graph. Solving the min-cut max-flow problem on this graph yields the segmentation for all timepoints in a single step. By segmenting all timepoints simultaneously, a consistent and atrophy-sensitive segmentation is obtained. The application to hippocampal atrophy measurement in 568 image pairs (Baseline and Month 12 follow-up) as well as 362 image triplets (Baseline, Month 12, and Month 24) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) confirms previous findings for atrophy in Alzheimer's disease (AD) and healthy aging. Highly significant correlations between hippocampal atrophy and clinical variables (Mini Mental State Examination, MMSE and Clinical Dementia Rating, CDR) were found and atrophy rates differ significantly according to subjects' ApoE genotype. Based on one year atrophy rates, a correct classification rate of 82 between AD and control subjects is achieved. Subjects that converted from Mild Cognitive Impairment (MCI) to AD after the period for which atrophy was measured (i.e., after the first 12 months) and subjects for whom conversion is yet to be identified were discriminated with a rate of 64 , a promising result with a view to clinical application. Power analysis shows that 67 and 206 subjects are needed for the AD and MCI groups respectively to detect a 25 change in volume loss with 80 power and 5 significance. We present a framework for robustly estimating registration between a 3D volume image and a 2D projection image and evaluate its precision and robustness in spine interventions for vertebral localization in the presence of anatomical deformation. The framework employs a normalized gradient information similarity metric and multi-start covariance matrix adaptation evolution strategy optimization with local-restarts, which provided improved robustness against deformation and content mismatch. The parallelized implementation allowed orders-of-magnitude acceleration in computation time and improved the robustness of registration via multi-start global optimization. Experiments involved a cadaver specimen and two CT datasets (supine and prone) and 36 C-arm fluoroscopy images acquired with the specimen in four positions (supine, prone, supine with lordosis, prone with kyphosis), three regions (thoracic, abdominal, and lumbar), and three levels of geometric magnification (1.7, 2.0, 2.4). Registration accuracy was evaluated in terms of projection distance error (PDE) between the estimated and true target points in the projection image, including 14 400 random trials (200 trials on the 72 registration scenarios) with initialization error up to ±200 mm and ±10°. The resulting median PDE was better than 0.1 mm in all cases, depending somewhat on the resolution of input CT and fluoroscopy images. The cadaver experiments illustrated the tradeoff between robustness and computation time, yielding a success rate of 99.993 in vertebral labeling (with 'success' defined as PDE <5 mm) using 1,718 664 ± 96 582 function evaluations computed in 54.0 ± 3.5 s on a mid-range GPU (nVidia, GeForce GTX690). Parameters yielding a faster search (e.g., fewer multi-starts) reduced robustness under conditions of large deformation and poor initialization (99.535 success for the same data registered in 13.1 s), but given good initialization (e.g., ±5 mm, assuming a robust initial run) the same registration could be solved with 99.993 success in 6.3 s. The ability to register CT to fluoroscopy in a manner robust to patient deformation could be valuable in applications such as radiation therapy, interventional radiology, and an assistant to target localization (e.g., vertebral labeling) in image-guided spine surgery. Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95 at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems. Purpose: Repeated brain MRI scans are performed in many clinical scenarios, such as follow up of patients with tumors and therapy response assessment. In this paper, the authors show an approach to utilize former scans of the patient for the acceleration of repeated MRI scans. Methods: The proposed approach utilizes the possible similarity of the repeated scans in longitudinal MRI studies. Since similarity is not guaranteed, sampling and reconstruction are adjusted during acquisition to match the actual similarity between the scans. The baseline MR scan is utilized both in the sampling stage, via adaptive sampling, and in the reconstruction stage, with weighted reconstruction. In adaptive sampling, k-space sampling locations are optimized during acquisition. Weighted reconstruction uses the locations of the nonzero coefficients in the sparse domains as a prior in the recovery process. The approach was tested on 2D and 3D MRI scans of patients with brain tumors. Results: The longitudinal adaptive compressed sensing MRI (LACS-MRI) scheme provides reconstruction quality which outperforms other CS-based approaches for rapid MRI. Examples are shown on patients with brain tumors and demonstrate improved spatial resolution. Compared with data sampled at the Nyquist rate, LACS-MRI exhibits signal-to-error ratio (SER) of 24.8 dB with undersampling factor of 16.6 in 3D MRI. Conclusions: The authors presented an adaptive method for image reconstruction utilizing similarity of scans in longitudinal MRI studies, where possible. The proposed approach can significantly reduce scanning time in many applications that consist of disease follow-up and monitoring of longitudinal changes in brain MRI. The work explores the use of denoising autoencoders (DAEs) for brain lesion detection, segmentation, and false-positive reduction. Stacked denoising autoencoders (SDAEs) were pretrained using a large number of unlabeled patient volumes and fine-tuned with patches drawn from a limited number of patients (n=20, 40, 65). The results show negligible loss in performance even when SDAE was fine-tuned using 20 labeled patients. Low grade glioma (LGG) segmentation was achieved using a transfer learning approach in which a network pretrained with high grade glioma data was fine-tuned using LGG image patches. The networks were also shown to generalize well and provide good segmentation on unseen BraTS 2013 and BraTS 2015 test data. The manuscript also includes the use of a single layer DAE, referred to as novelty detector (ND). ND was trained to accurately reconstruct nonlesion patches. The reconstruction error maps of test data were used to localize lesions. The error maps were shown to assign unique error distributions to various constituents of the glioma, enabling localization. The ND learns the nonlesion brain accurately as it was also shown to provide good segmentation performance on ischemic brain lesions in images from a different database. A significant proportion of patients scanned in a clinical setting have follow-up scans. We show in this work that such longitudinal scans alone can be used as a form of “free” self-supervision for training a deep network. We demonstrate this self-supervised learning for the case of T2-weighted sagittal lumbar Magnetic Resonance Images (MRIs). A Siamese convolutional neural network (CNN) is trained using two losses: (i) a contrastive loss on whether the scan is of the same person (i.e. longitudinal) or not, together with (ii) a classification loss on predicting the level of vertebral bodies. The performance of this pre-trained network is then assessed on a grading classification task. We experiment on a dataset of 1016 subjects, 423 possessing follow-up scans, with the end goal of learning the disc degeneration radiological gradings attached to the intervertebral discs. We show that the performance of the pre-trained CNN on the supervised classification task is (i) superior to that of a network trained from scratch; and (ii) requires far fewer annotated training samples to reach an equivalent performance to that of the network trained from scratch. Abstract Enlarged perivascular spaces (EPVS) in the brain are an emerging imaging marker for cerebral small vessel disease, and have been shown to be related to increased risk of various neurological diseases, including stroke and dementia. Automated quantification of EPVS would greatly help to advance research into its etiology and its potential as a risk indicator of disease. We propose a convolutional network regression method to quantify the extent of EPVS in the basal ganglia from 3D brain MRI. We first segment the basal ganglia and subsequently apply a 3D convolutional regression network designed for small object detection within this region of interest. The network takes an image as input, and outputs a quantification score of EPVS. The network has significantly more convolution operations than pooling ones and no final activation, allowing it to span the space of real numbers. We validated our approach using a dataset of 2000 brain MRI scans scored visually. Experiments with varying sizes of training and test sets showed that a good performance can be achieved with a training set of only 200 scans. With a training set of 1000 scans, the intraclass correlation coefficient (ICC) between our scoring method and the expert’s visual score was 0.74. Our method outperforms by a large margin - more than 0.10 - four more conventional automated approaches based on intensities, scale-invariant feature transform, and random forest. We show that the network learns the structures of interest and investigate the influence of hyper-parameters on the performance. We also evaluate the reproducibility of our network using a set of 60 subjects scanned twice (scan-rescan reproducibility). On this set our network achieves an ICC of 0.93, while the intrarater agreement reaches 0.80. Furthermore, the automated EPVS scoring correlates similarly to age as visual scoring. With the advances and increasing sophistication in data collection techniques, we are facing with large amounts of data collected from multiple heterogeneous sources in many applications. For example, in the study of Alzheimer's Disease (AD), different types of measurements such as neuroimages, gene protein expression data, genetic data etc. are often collected and analyzed together for improved predictive power. It is believed that a joint learning of multiple data sources is beneficial as different data sources may contain complementary information, and feature-pruning and data source selection are critical for learning interpretable models from high-dimensional data. Very often the collected data comes with block-wise missing entries; for example, a patient without the MRI scan will have no information in the MRI data block, making his her overall record incomplete. There has been a growing interest in the data mining community on expanding traditional techniques for single-source complete data analysis to the study of multi-source incomplete data. The key challenge is how to effectively integrate information from multiple heterogeneous sources in the presence of block-wise missing data. In this paper we first investigate the situation of complete data and present a unified bi-level" learning model for multi-source data. Then we give a natural extension of this model to the more challenging case with incomplete data. Our major contributions are threefold: (1) the proposed models handle both feature-level and source-level analysis in a unified formulation and include several existing feature learning approaches as special cases; (2) the model for incomplete data avoids direct imputation of the missing elements and thus provides superior performances. Moreover, it can be easily generalized to other applications with block-wise missing data sources; (3) efficient optimization algorithms are presented for both the complete and incomplete models. We have performed comprehensive evaluations of the proposed models on the application of AD diagnosis. Our proposed models compare favorably against existing approaches.