Brain segmentation is a fundamental first step in neuroimage analysis. In the case of fetal MRI, it is particularly challenging and important due to the arbitrary orientation of the fetus, organs that surround the fetal head, and intermittent fetal motion. Several promising methods have been proposed but are limited in their performance in challenging cases and in real-time segmentation. We aimed to develop a fully automatic segmentation method that independently segments sections of the fetal brain in 2D fetal MRI slices in real-time. To this end, we developed and evaluated a deep fully convolutional neural network based on 2D U-net and autocontext, and compared it to two alternative fast methods based on 1) a voxelwise fully convolutional network and 2) a method based on SIFT features, random forest and conditional random field. We trained the networks with manual brain masks on 250 stacks of training images, and tested on 17 stacks of normal fetal brain images as well as 18 stacks of extremely challenging cases based on extreme motion, noise, and severely abnormal brain shape. Experimental results show that our U-net approach outperformed the other methods and achieved average Dice metrics of 96.52% and 78.83% in the normal and challenging test sets, respectively. With an unprecedented performance and a test run time of about 1 second, our network can be used to segment the fetal brain in real-time while fetal MRI slices are being acquired. This can enable real-time motion tracking, motion detection, and 3D reconstruction of fetal brain MRI.
Brain extraction or whole brain segmentation is an important first step in many of the neuroimage analysis pipelines. The accuracy and the robustness of brain extraction, therefore, are crucial for the accuracy of the entire brain analysis process. The state-of-the-art brain extraction techniques rely heavily on the accuracy of alignment or registration between brain atlases and query brain anatomy, and/or make assumptions about the image geometry, and therefore have limited success when these assumptions do not hold or image registration fails. With the aim of designing an accurate, learning-based, geometry-independent, and registration-free brain extraction tool, in this paper, we present a technique based on an auto-context convolutional neural network (CNN), in which intrinsic local and global image features are learned through 2-D patches of different window sizes. We consider two different architectures: 1) a voxelwise approach based on three parallel 2-D convolutional pathways for three different directions (axial, coronal, and sagittal) that implicitly learn 3-D image information without the need for computationally expensive 3-D convolutions and 2) a fully convolutional network based on the U-net architecture. Posterior probability maps generated by the networks are used iteratively as context information along with the original image patches to learn the local shape and connectedness of the brain to extract it from non-brain tissue. The brain extraction results we have obtained from our CNNs are superior to the recently reported results in the literature on two publicly available benchmark data sets, namely, LPBA40 and OASIS, in which we obtained the Dice overlap coefficients of 97.73% and 97.62%, respectively. Significant improvement was achieved via our auto-context algorithm. Furthermore, we evaluated the performance of our algorithm in the challenging problem of extracting arbitrarily oriented fetal brains in reconstructed fetal brain magnetic resonance imaging (MRI) data sets. In this application, our voxelwise auto-context CNN performed much better than the other methods (Dice coefficient: 95.97%), where the other methods performed poorly due to the non-standard orientation and geometry of the fetal brain in MRI. Through training, our method can provide accurate brain extraction in challenging applications. This, in turn, may reduce the problems associated with image registration in segmentation tasks.
Most fetal brain MRI reconstruction algorithms rely only on brain tissue-relevant voxels of low-resolution (LR) images to enhance the quality of inter-slice motion correction and image reconstruction. Consequently the fetal brain needs to be localized and extracted as a first step, which is usually a laborious and time consuming manual or semi-automatic task. We have proposed in this work to use age-matched template images as prior knowledge to automatize brain localization and extraction. This has been achieved through a novel automatic brain localization and extraction method based on robust template-to-slice block matching and deformable slice-to-template registration. Our template-based approach has also enabled the reconstruction of fetal brain images in standard radiological anatomical planes in a common coordinate space. We have integrated this approach into our new reconstruction pipeline that involves intensity normalization, inter-slice motion correction, and super-resolution (SR) reconstruction. To this end we have adopted a novel approach based on projection of every slice of the LR brain masks into the template space using a fusion strategy. This has enabled the refinement of brain masks in the LR images at each motion correction iteration. The overall brain localization and extraction algorithm has shown to produce brain masks that are very close to manually drawn brain masks, showing an average Dice overlap measure of 94.5%. We have also demonstrated that adopting a slice-to-template registration and propagation of the brain mask slice-by-slice leads to a significant improvement in brain extraction performance compared to global rigid brain extraction and consequently in the quality of the final reconstructed images. Ratings performed by two expert observers show that the proposed pipeline can achieve similar reconstruction quality to reference reconstruction based on manual slice-by-slice brain extraction. The proposed brain mask refinement and reconstruction method has shown to provide promising results in automatic fetal brain MRI segmentation and volumetry in 26 fetuses with gestational age range of 23 to 38 weeks.
In this work, we introduce a novel motion-robust spatially constrained parameter estimation (MOSCOPE) technique for kidney diffusion-weighted MRI. The proposed motion compensation technique does not require a navigator, trigger, or breath-hold but only uses the intrinsic features of the acquired data to track and compensate for motion to reconstruct precise models of the renal diffusion signal. We have developed a technique for physiological motion tracking based on robust state estimation and sequential registration of diffusion sensitized slices acquired within 200ms. This allows a sampling rate of 5Hz for state estimation in motion tracking that is sufficiently faster than both respiratory and cardiac motion rates in children and adults, which range between 0.8 to 0.2Hz, and 2.5 to 1Hz, respectively. We then apply the estimated motion parameters to data from each slice and use motion-compensated data for 1) robust intra-voxel incoherent motion (IVIM) model estimation in the kidney using a spatially constrained model fitting approach, and 2) robust weighted least squares estimation of the diffusion tensor model. Experimental results, including precision of IVIM model parameters using bootstrap-sampling and whole kidney tractography, showed significant improvement in precision and accuracy of these models using the proposed method compared to models based on the original data and volumetric registration.
In magnetic resonance (MR), hardware limitations, scan time constraints, and patient movement often result in the acquisition of anisotropic 3-D MR images with limited spatial resolution in the out-of-plane views. Our goal is to construct an isotropic high-resolution (HR) 3-D MR image through upsampling and fusion of orthogonal anisotropic input scans. We propose a multiframe super-resolution (SR) reconstruction technique based on sparse representation of MR images. Our proposed algorithm exploits the correspondence between the HR slices and the low-resolution (LR) sections of the orthogonal input scans as well as the self-similarity of each input scan to train pairs of overcomplete dictionaries that are used in a sparse-land local model to upsample the input scans. The upsampled images are then combined using wavelet fusion and error backprojection to reconstruct an image. Features are learned from the data and no extra training set is needed. Qualitative and quantitative analyses were conducted to evaluate the proposed algorithm using simulated and clinical MR scans. Experimental results show that the proposed algorithm achieves promising results in terms of peak signal-to-noise ratio, structural similarity image index, intensity profiles, and visualization of small structures obscured in the LR imaging process due to partial volume effects. Our novel SR algorithm outperforms the nonlocal means (NLM) method using self-similarity, NLM method using self-similarity and image prior, self-training dictionary learning-based SR method, averaging of upsampled scans, and the wavelet fusion method. Our SR algorithm can reduce through-plane partial volume artifact by combining multiple orthogonal MR scans, and thus can potentially improve medical image analysis, research, and clinical diagnosis.
Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new algorithm to construct a spatiotemporal atlas from MRI of 81 normal fetuses scanned between 19 and 39 weeks of gestation and labeled the structures of the developing brain. We evaluated the use of this atlas and additional individual fetal brain MRI atlases for completely automatic multi-atlas segmentation of fetal brain MRI. The atlas is available online as a reference for anatomy and for registration and segmentation, to aid in connectivity analysis, and for groupwise and longitudinal analysis of early brain growth.
Diffusion weighted magnetic resonance imaging, or DWI, is one of the most promising tools for the analysis of neural microstructure and the structural connectome of the human brain. The application of DWI to map early development of the human connectome in-utero, however, is challenged by intermittent fetal and maternal motion that disrupts the spatial correspondence of data acquired in the relatively long DWI acquisitions. Fetuses move continuously during DWI scans. Reliable and accurate analysis of the fetal brain structural connectome requires careful compensation of motion effects and robust reconstruction to avoid introducing bias based on the degree of fetal motion. In this paper we introduce a novel robust algorithm to reconstruct in-vivo diffusion-tensor MRI (DTI) of the moving fetal brain and show its effect on structural connectivity analysis. The proposed algorithm involves multiple steps of image registration incorporating a dynamic registration-based motion tracking algorithm to restore the spatial correspondence of DWI data at the slice level and reconstruct DTI of the fetal brain in the standard (atlas) coordinate space. A weighted linear least squares approach is adapted to remove the effect of intra-slice motion and reconstruct DTI from motion-corrected data. The proposed algorithm was tested on data obtained from 21 healthy fetuses scanned in-utero at 22-38 weeks gestation. Significantly higher fractional anisotropy values in fiber-rich regions, and the analysis of whole-brain tractography and group structural connectivity, showed the efficacy of the proposed method compared to the analyses based on original data and previously proposed methods. The results of this study show that slice-level motion correction and robust reconstruction is necessary for reliable in-vivo structural connectivity analysis of the fetal brain. Connectivity analysis based on graph theoretic measures show high degree of modularity and clustering, and short average characteristic path lengths indicative of small-worldness property of the fetal brain network. These findings comply with previous findings in newborns and a recent study on fetuses. The proposed algorithm can provide valuable information from DWI of the fetal brain not available in the assessment of the original 2D slices and may be used to more reliably study the developing fetal brain connectome.
PURPOSE: Current diagnosis of fetal posterior fossa anomalies by sonography and conventional MRI is limited by fetal position, motion, and by two-dimensional (2D), rather than three-dimensional (3D), representation. In this study, we aimed to validate the use of a novel magnetic resonance imaging (MRI) technique, 3D super-resolution motion-corrected MRI, to image the fetal posterior fossa.
METHODS: From a database of pregnant women who received fetal MRIs at our institution, images of 49 normal fetal brains were reconstructed. Six measurements of the cerebellum, vermis, and pons were obtained for all cases on 2D conventional and 3D reconstructed MRI, and the agreement between the two methods was determined using concordance correlation coefficients. Concordance of axial and coronal measurements of the transcerebellar diameter was also assessed within each method.
RESULTS: Between the two methods, the concordance of measurements was high for all six structures (P < .001), and was highest for larger structures such as the transcerebellar diameter. Within each method, agreement of axial and coronal measurements of the transcerebellar diameter was superior in 3D reconstructed MRI compared to 2D conventional MRI (P < .001).
CONCLUSIONS: This comparison study validates the use of 3D super-resolution motion-corrected MRI for imaging the fetal posterior fossa, as this technique results in linear measurements that have high concordance with 2D conventional MRI measurements. Lengths of the transcerebellar diameter measured within a 3D reconstruction are more concordant between imaging planes, as they correct for fetal motion and orthogonal slice acquisition. This technique will facilitate further study of fetal abnormalities of the posterior fossa.
PURPOSE: To evaluate the feasibility of using diffusion-weighted magnetic resonance imaging (DW-MRI) to assess the fetal lung apparent diffusion coefficient (ADC) at 3 Tesla (T).
MATERIALS AND METHODS: Seventy-one pregnant women (32 second trimester, 39 third trimester) were scanned with a twice-refocused Echo-planar diffusion-weighted imaging sequence with 6 different b-values in 3 orthogonal diffusion orientations at 3T. After each scan, a region-of-interest (ROI) mask was drawn to select a region in the fetal lung and an automated robust maximum likelihood estimation algorithm was used to compute the ADC parameter. The amount of motion in each scan was visually rated.
RESULTS: When scans with unacceptable levels of motion were eliminated, the lung ADC values showed a strong association with gestational age (P < 0.01), increasing dramatically between 16 and 27 weeks and then achieving a plateau around 27 weeks.
CONCLUSION: We show that to get reliable estimates of ADC values of fetal lungs, a multiple b-value acquisition, where motion is either corrected or considered, can be performed. J. Magn. Reson. Imaging 2016;44:1650-1655.
Simultaneous multi-slice (SMS) echo-planar imaging has had a huge impact on the acceleration and routine use of diffusion-weighted MRI (DWI) in neuroimaging studies in particular the human connectome project; but also holds the potential to facilitate DWI of moving subjects, as proposed by the new technique developed in this paper. We present a novel registration-based motion tracking technique that takes advantage of the multi-plane coverage of the anatomy by simultaneously acquired slices to enable robust reconstruction of neural microstructure from SMS DWI of moving subjects. Our technique constitutes three main components: 1) motion tracking and estimation using SMS registration, 2) detection and rejection of intra-slice motion, and 3) robust reconstruction. Quantitative results from 14 volunteer subject experiments and the analysis of motion-corrupted SMS DWI of 6 children indicate robust reconstruction in the presence of continuous motion and the potential to extend the use of SMS DWI in very challenging populations.
In magnetic resonance (MR), hardware limitation, scanning time, and patient comfort often result in the acquisition of anisotropic 3-D MR images. Enhancing image resolution is desired but has been very challenging in medical image processing. Super resolution reconstruction based on sparse representation and overcomplete dictionary has been lately employed to address this problem; however, these methods require extra training sets, which may not be always available. This paper proposes a novel single anisotropic 3-D MR image upsampling method via sparse representation and overcomplete dictionary that is trained from in-plane high resolution slices to upsample in the out-of-plane dimensions. The proposed method, therefore, does not require extra training sets. Abundant experiments, conducted on simulated and clinical brain MR images, show that the proposed method is more accurate than classical interpolation. When compared to a recent upsampling method based on the nonlocal means approach, the proposed method did not show improved results at low upsampling factors with simulated images, but generated comparable results with much better computational efficiency in clinical cases. Therefore, the proposed approach can be efficiently implemented and routinely used to upsample MR images in the out-of-planes views for radiologic assessment and postacquisition processing.
Acquisition of a series of anisotropically oversampled acquisitions (so-called anisotropic "snapshots") and reconstruction in the image space has recently been proposed to increase the spatial resolution in diffusion weighted imaging (DWI), providing a theoretical 8x acceleration at equal signal-to-noise ratio (SNR) compared to conventional dense k-space sampling. However, in most works, each DW image is reconstructed separately and the fact that the DW images constitute different views of the same anatomy is ignored. In addition, current approaches are limited by their inability to reconstruct a high resolution (HR) acquisition from snapshots with different subsets of diffusion gradients: an isotropic HR gradient image cannot be reconstructed if one .of its anisotropic snapshots is missing, for example due to intra-scan motion, even if other snapshots for this gradient were successfully acquired. In this work, we propose a novel multi-snapshot DWI reconstruction technique that simultaneously achieves HR reconstruction and local tissue model estimation while enabling reconstruction from snapshots containing different subsets of diffusion gradients, providing increased robustness to patient motion and potential for acceleration. Our approach is formalized as a joint probabilistic model with missing observations, from which interactions between missing snapshots, HR reconstruction and a generic tissue model naturally emerge. We evaluate our approach with synthetic simulations, simulated multi-snapshot scenario and in vivo multi-snapshot imaging. We show that (1) our combined approach ultimately provides both better HR reconstruction and better tissue model estimation and (2) the error in the case of missing snapshots can be quantified. Our novel multi-snapshot technique will enable improved high spatial characterization of the brain connectivity and microstructure in vivo.
PURPOSE: To compare and evaluate the use of super-resolution reconstruction (SRR), in frequency, image, and wavelet domains, to reduce through-plane partial voluming effects in magnetic resonance imaging.
METHODS: The reconstruction of an isotropic high-resolution image from multiple thick-slice scans has been investigated through techniques in frequency, image, and wavelet domains. Experiments were carried out with thick-slice T2-weighted fast spin echo sequence on the Academic College of Radiology MRI phantom, where the reconstructed images were compared to a reference high-resolution scan using peak signal-to-noise ratio (PSNR), structural similarity image metric (SSIM), mutual information (MI), and the mean absolute error (MAE) of image intensity profiles. The application of super-resolution reconstruction was then examined in retrospective processing of clinical neuroimages of ten pediatric patients with tuberous sclerosis complex (TSC) to reduce through-plane partial voluming for improved 3D delineation and visualization of thin radial bands of white matter abnormalities.
RESULTS: Quantitative evaluation results show improvements in all evaluation metrics through super-resolution reconstruction in the frequency, image, and wavelet domains, with the highest values obtained from SRR in the image domain. The metric values for image-domain SRR versus the original axial, coronal, and sagittal images were PSNR = 32.26 vs 32.22, 32.16, 30.65; SSIM = 0.931 vs 0.922, 0.924, 0.918; MI = 0.871 vs 0.842, 0.844, 0.831; and MAE = 5.38 vs 7.34, 7.06, 6.19. All similarity metrics showed high correlations with expert ranking of image resolution with MI showing the highest correlation at 0.943. Qualitative assessment of the neuroimages of ten TSC patients through in-plane and out-of-plane visualization of structures showed the extent of partial voluming effect in a real clinical scenario and its reduction using SRR. Blinded expert evaluation of image resolution in resampled out-of-plane views consistently showed the superiority of SRR compared to original axial and coronal image acquisitions.
CONCLUSIONS: Thick-slice 2D T2-weighted MRI scans are part of many routine clinical protocols due to their high signal-to-noise ratio, but are often severely affected by through-plane partial voluming effects. This study shows that while radiologic assessment is performed in 2D on thick-slice scans, super-resolution MRI reconstruction techniques can be used to fuse those scans to generate a high-resolution image with reduced partial voluming for improved postacquisition processing. Qualitative and quantitative evaluation showed the efficacy of all SRR techniques with the best results obtained from SRR in the image domain. The limitations of SRR techniques are uncertainties in modeling the slice profile, density compensation, quantization in resampling, and uncompensated motion between scans.
Writing a compelling grant application is a skill that is crucial to conducting high-quality and high-impact scientific research. A successful grant proposal provides the resources necessary to foster activity in an important area of investigation. A concise and practical overview of the anatomy and art of grant writing is provided in this article, along with citations to resources that are particularly useful for junior investigators.
The development and identification of best methods in fetal brain MRI analysis is crucial as we expect an outburst of studies on groupwise and longitudinal analysis of early brain development in the upcoming years. To address this critical need, in this paper, we have developed a mathematical framework for the construction of an unbiased deformable spatiotemporal atlas of the fetal brain MRI and compared it to alternative configurations in terms of similarity metrics and deformation models. Our contributions are twofold: first we suggest a novel approach to fetal brain spatiotemporal atlas construction that shows high capability in capturing anatomic variation between subjects; and second, within our atlas construction framework we evaluate and compare a set of plausible configurations for inter-subject fetal brain MRI registration and identify the most accurate approach that can potentially lead to most accurate results in population atlas construction, atlas-based segmentation, and group analysis. Our evaluation results indicate that symmetric diffeomorphic deformable registration with cross correlation similarity metric outperforms other configurations in this application and results in sharp unbiased atlases that can be used in fetal brain MRI analysis.
Ali Gholipour, Judith A Estroff, Carol E Barnewolt, Richard L Robertson, Ellen P Grant, Borjan Gagoski, Simon K Warfield, Onur Afacan, Susan A Connolly, Jeffrey J Neil, Adam Wolfberg, and Robert V Mulkern. 2014. “Fetal MRI: A Technical Update with Educational Aspirations.” Concepts Magn Reson Part A Bridg Educ Res, 43, 6, Pp. 237-266.Abstract
Fetal magnetic resonance imaging (MRI) examinations have become well-established procedures at many institutions and can serve as useful adjuncts to ultrasound (US) exams when diagnostic doubts remain after US. Due to fetal motion, however, fetal MRI exams are challenging and require the MR scanner to be used in a somewhat different mode than that employed for more routine clinical studies. Herein we review the techniques most commonly used, and those that are available, for fetal MRI with an emphasis on the physics of the techniques and how to deploy them to improve success rates for fetal MRI exams. By far the most common technique employed is single-shot T2-weighted imaging due to its excellent tissue contrast and relative immunity to fetal motion. Despite the significant challenges involved, however, many of the other techniques commonly employed in conventional neuro- and body MRI such as T1 and T2*-weighted imaging, diffusion and perfusion weighted imaging, as well as spectroscopic methods remain of interest for fetal MR applications. An effort to understand the strengths and limitations of these basic methods within the context of fetal MRI is made in order to optimize their use and facilitate implementation of technical improvements for the further development of fetal MR imaging, both in acquisition and post-processing strategies.