Unpaired deep learning for pharmacokinetic parameter estimation from dynamic contrast-enhanced MRI without AIF measurements.

DCE-MRI provides information about vascular permeability and tissue perfusion through the acquisition of pharmacokinetic parameters. However, traditional methods for estimating these pharmacokinetic parameters involve fitting tracer kinetic models, which often suffer from computational complexity and low accuracy due to noisy arterial input function (AIF) measurements. Although some deep learning approaches have been proposed to tackle these challenges, most existing methods rely on supervised learning that requires paired input DCE-MRI and labeled pharmacokinetic parameter maps. This dependency on labeled data introduces significant time and resource constraints and potential noise in the labels, making supervised learning methods often impractical. To address these limitations, we present a novel unpaired deep learning method for estimating pharmacokinetic parameters and the AIF using a physics-driven CycleGAN approach. Our proposed CycleGAN framework is designed based on the underlying physics model, resulting in a simpler architecture with a single generator and discriminator pair. Crucially, our experimental results indicate that our method does not necessitate separate AIF measurements and produces more reliable pharmacokinetic parameters than other techniques.

Deep learning model for diagnosing gastric mucosal lesions using endoscopic images: development, validation, and method comparison.

BACKGROUND AND AIMS: Endoscopic differential diagnoses of gastric mucosal lesions (benign gastric ulcer, early gastric cancer [EGC], and advanced gastric cancer) remain challenging. We aimed to develop and validate convolutional neural network-based artificial intelligence (AI) models: lesion detection, differential diagnosis (AI-DDx), and invasion depth (AI-ID; pT1a vs pT1b among EGC) models. METHODS: This study included 1366 consecutive patients with gastric mucosal lesions from 2 referral centers in Korea. One representative endoscopic image from each patient was used. Histologic diagnoses were set as the criterion standard. Performance of the AI-DDx (training/internal/external validation set, 1009/112/245) and AI-ID (training/internal/external validation set, 620/68/155) was compared with visual diagnoses by independent endoscopists (stratified by novice [<1 year of experience], intermediate [2-3 years of experience], and expert [>5 years of experience]) and EUS results, respectively. RESULTS: The AI-DDx showed good diagnostic performance for both internal (area under the receiver operating characteristic curve [AUROC] = .86) and external validation (AUROC = .86). The performance of the AI-DDx was better than that of novice (AUROC = .82, P = .01) and intermediate endoscopists (AUROC = .84, P = .02) but was comparable with experts (AUROC = .89, P = .12) in the external validation set. The AI-ID showed a fair performance in both internal (AUROC = .78) and external validation sets (AUROC = .73), which were significantly better than EUS results performed by experts (internal validation, AUROC = .62; external validation, AUROC = .56; both P < .001). CONCLUSIONS: The AI-DDx was comparable with experts and outperformed novice and intermediate endoscopists for the differential diagnosis of gastric mucosal lesions. The AI-ID performed better than EUS for evaluation of invasion depth.

Unsupervised Deep Learning Methods for Biological Image Reconstruction and Enhancement: An overview from a signal processing perspective.

Recently, deep learning approaches have become the main research frontier for biological image reconstruction and enhancement problems thanks to their high performance, along with their ultra-fast inference times. However, due to the difficulty of obtaining matched reference data for supervised learning, there has been increasing interest in unsupervised learning approaches that do not need paired reference data. In particular, self-supervised learning and generative models have been successfully used for various biological imaging applications. In this paper, we overview these approaches from a coherent perspective in the context of classical inverse problems, and discuss their applications to biological imaging, including electron, fluorescence and deconvolution microscopy, optical diffraction tomography and functional neuroimaging.

Deep learning-based denoising algorithm in comparison to iterative reconstruction and filtered back projection: a 12-reader phantom study.

OBJECTIVES: (1) To compare low-contrast detectability of a deep learning-based denoising algorithm (DLA) with ADMIRE and FBP, and (2) to compare image quality parameters of DLA with those of reconstruction methods from two different CT vendors (ADMIRE, IMR, and FBP). MATERIALS AND METHODS: Using abdominal CT images of 100 patients reconstructed via ADMIRE and FBP, we trained DLA by feeding FBP images as input and ADMIRE images as the ground truth. To measure the low-contrast detectability, the randomized repeat scans of Catphan® phantom were performed under various conditions of radiation exposures. Twelve radiologists evaluated the presence/absence of a target on a five-point confidence scale. The multi-reader multi-case area under the receiver operating characteristic curve (AUC) was calculated, and non-inferiority tests were performed. Using American College of Radiology CT accreditation phantom, contrast-to-noise ratio, target transfer function, noise magnitude, and detectability index (d') of DLA, ADMIRE, IMR, and FBPs were computed. RESULTS: The AUC of DLA in low-contrast detectability was non-inferior to that of ADMIRE (p < .001) and superior to that of FBP (p < .001). DLA improved the image quality in terms of all physical measurements compared to FBPs from both CT vendors and showed profiles of physical measurements similar to those of ADMIRE. CONCLUSIONS: The low-contrast detectability of the proposed deep learning-based denoising algorithm was non-inferior to that of ADMIRE and superior to that of FBP. The DLA could successfully improve image quality compared with FBP while showing the similar physical profiles of ADMIRE. KEY POINTS: • Low-contrast detectability in the images denoised using the deep learning algorithm was non-inferior to that in the images reconstructed using standard algorithms. • The proposed deep learning algorithm showed similar profiles of physical measurements to advanced iterative reconstruction algorithm (ADMIRE).

Improving the Reliability of Pharmacokinetic Parameters at Dynamic Contrast-enhanced MRI in Astrocytomas: A Deep Learning Approach.

Background Pharmacokinetic (PK) parameters obtained from dynamic contrast agent-enhanced (DCE) MRI evaluates the microcirculation permeability of astrocytomas, but the unreliability from arterial input function (AIF) remains a challenge. Purpose To develop a deep learning model that improves the reliability of AIF for DCE MRI and to validate the reliability and diagnostic performance of PK parameters by using improved AIF in grading astrocytomas. Materials and Methods This retrospective study included 386 patients (mean age, 52 years ± 16 [standard deviation]; 226 men) with astrocytomas diagnosed with histopathologic analysis who underwent dynamic susceptibility contrast (DSC)-enhanced and DCE MRI preoperatively from April 2010 to January 2018. The AIF was obtained from each sequence: AIF obtained from DSC-enhanced MRI (AIFDSC) and AIF measured at DCE MRI (AIFDCE). The model was trained to translate AIFDCE into AIFDSC, and after training, outputted neural-network-generated AIF (AIFgenerated DSC) with input AIFDCE. By using the three different AIFs, volume transfer constant (Ktrans), fractional volume of extravascular extracellular space (Ve), and vascular plasma space (Vp) were averaged from the tumor areas in the DCE MRI. To validate the model, intraclass correlation coefficients and areas under the receiver operating characteristic curve (AUCs) of the PK parameters in grading astrocytomas were compared by using different AIFs. Results The AIF-generated, DSC-derived PK parameters showed higher AUCs in grading astrocytomas than those derived from AIFDCE (mean Ktrans, 0.88 [95% confidence interval {CI}: 0.81, 0.93] vs 0.72 [95% CI: 0.63, 0.79], P = .04; mean Ve, 0.87 [95% CI: 0.79, 0.92] vs 0.70 [95% CI: 0.61, 0.77], P = .049, respectively). Ktrans and Ve showed higher intraclass correlation coefficients for AIFgenerated DSC than for AIFDCE (0.91 vs 0.38, P < .001; and 0.86 vs 0.60, P < .001, respectively). In AIF analysis, baseline signal intensity (SI), maximal SI, and wash-in slope showed higher intraclass correlation coefficients with AIFgenerated DSC than AIFDCE (0.77 vs 0.29, P < .001; 0.68 vs 0.42, P = .003; and 0.66 vs 0.45, P = .01, respectively. Conclusion A deep learning algorithm improved both reliability and diagnostic performance of MRI pharmacokinetic parameters for differentiating astrocytoma grades. © RSNA, 2020 Online supplemental material is available for this article.

Quantitative susceptibility map reconstruction using annihilating filter-based low-rank Hankel matrix approach.

PURPOSE: Quantitative susceptibility mapping (QSM) inevitably suffers from streaking artifacts caused by zeros on the conical surface of the dipole kernel in k-space. This work proposes a novel and accurate QSM reconstruction method based on k-space low-rank Hankel matrix constraint, avoiding the over-smoothing problem and streaking artifacts. THEORY AND METHODS: Based on the recent theory of annihilating filter-based low-rank Hankel matrix approach (ALOHA), QSM is formulated as deconvolution under low-rank Hankel matrix constraint in the k-space. The computational complexity and the high memory burden were reduced by successive reconstruction of 2-D planes along 3 independent axes of the 3-D phase image in Fourier domain. Feasibility of the proposed method was tested on a simulated phantom and human data and were compared with existing QSM reconstruction methods. RESULTS: The proposed ALOHA-QSM effectively reduced streaking artifacts and accurately estimated susceptibility values in deep gray matter structures, compared to the existing QSM methods. CONCLUSIONS: The suggested ALOHA-QSM algorithm successfully solves the 3-dimensional QSM dipole inversion problem using k-space low rank property with no anatomical constraint. ALOHA-QSM can provide detailed brain structures and accurate susceptibility values with no streaking artifacts.

Image Reconstruction: From Sparsity to Data-adaptive Methods and Machine Learning.

The field of medical image reconstruction has seen roughly four types of methods. The first type tended to be analytical methods, such as filtered back-projection (FBP) for X-ray computed tomography (CT) and the inverse Fourier transform for magnetic resonance imaging (MRI), based on simple mathematical models for the imaging systems. These methods are typically fast, but have suboptimal properties such as poor resolution-noise trade-off for CT. A second type is iterative reconstruction methods based on more complete models for the imaging system physics and, where appropriate, models for the sensor statistics. These iterative methods improved image quality by reducing noise and artifacts. The FDA-approved methods among these have been based on relatively simple regularization models. A third type of methods has been designed to accommodate modified data acquisition methods, such as reduced sampling in MRI and CT to reduce scan time or radiation dose. These methods typically involve mathematical image models involving assumptions such as sparsity or low-rank. A fourth type of methods replaces mathematically designed models of signals and systems with data-driven or adaptive models inspired by the field of machine learning. This paper focuses on the two most recent trends in medical image reconstruction: methods based on sparsity or low-rank models, and data-driven methods based on machine learning techniques.

Artificial Intelligence in Health Care: Current Applications and Issues.

In recent years, artificial intelligence (AI) technologies have greatly advanced and become a reality in many areas of our daily lives. In the health care field, numerous efforts are being made to implement the AI technology for practical medical treatments. With the rapid developments in machine learning algorithms and improvements in hardware performances, the AI technology is expected to play an important role in effectively analyzing and utilizing extensive amounts of health and medical data. However, the AI technology has various unique characteristics that are different from the existing health care technologies. Subsequently, there are a number of areas that need to be supplemented within the current health care system for the AI to be utilized more effectively and frequently in health care. In addition, the number of medical practitioners and public that accept AI in the health care is still low; moreover, there are various concerns regarding the safety and reliability of AI technology implementations. Therefore, this paper aims to introduce the current research and application status of AI technology in health care and discuss the issues that need to be resolved.

Structured Low-Rank Algorithms: Theory, Magnetic Resonance Applications, and Links to Machine Learning.

In this survey, we provide a detailed review of recent advances in the recovery of continuous domain multidimensional signals from their few non-uniform (multichannel) measurements using structured low-rank matrix completion formulation. This framework is centered on the fundamental duality between the compactness (e.g., sparsity) of the continuous signal and the rank of a structured matrix, whose entries are functions of the signal. This property enables the reformulation of the signal recovery as a low-rank structured matrix completion, which comes with performance guarantees. We will also review fast algorithms that are comparable in complexity to current compressed sensing methods, which enables the application of the framework to large-scale magnetic resonance (MR) recovery problems. The remarkable flexibility of the formulation can be used to exploit signal properties that are difficult to capture by current sparse and low-rank optimization strategies. We demonstrate the utility of the framework in a wide range of MR imaging (MRI) applications, including highly accelerated imaging, calibration-free acquisition, MR artifact correction, and ungated dynamic MRI.

k-Space deep learning for reference-free EPI ghost correction.

PURPOSE: Nyquist ghost artifacts in echo planar imaging (EPI) are originated from phase mismatch between the even and odd echoes. However, conventional correction methods using reference scans often produce erroneous results especially in high-field MRI due to the nonlinear and time-varying local magnetic field changes. Recently, it was shown that the problem of ghost correction can be reformulated as k-space interpolation problem that can be solved using structured low-rank Hankel matrix approaches. Another recent work showed that data driven Hankel matrix decomposition can be reformulated to exhibit similar structures as deep convolutional neural network. By synergistically combining these findings, we propose a k-space deep learning approach that immediately corrects the phase mismatch without a reference scan in both accelerated and non-accelerated EPI acquisitions. THEORY AND METHODS: To take advantage of the even and odd-phase directional redundancy, the k-space data are divided into 2 channels configured with even and odd phase encodings. The redundancies between coils are also exploited by stacking the multi-coil k-space data into additional input channels. Then, our k-space ghost correction network is trained to learn the interpolation kernel to estimate the missing virtual k-space data. For the accelerated EPI data, the same neural network is trained to directly estimate the interpolation kernels for missing k-space data from both ghost and subsampling. RESULTS: Reconstruction results using 3T and 7T in vivo data showed that the proposed method outperformed the image quality compared to the existing methods, and the computing time is much faster. CONCLUSIONS: The proposed k-space deep learning for EPI ghost correction is highly robust and fast, and can be combined with acceleration, so that it can be used as a promising correction tool for high-field MRI without changing the current acquisition protocol.

MRI artifact correction using sparse + low-rank decomposition of annihilating filter-based hankel matrix.

PURPOSE: Magnetic resonance imaging (MRI) artifacts are originated from various sources including instability of an magnetic resonance (MR) system, patient motion, inhomogeneities of gradient fields, and so on. Such MRI artifacts are usually considered as irreversible, so additional artifact-free scan or navigator scan is necessary. To overcome these limitations, this article proposes a novel compressed sensing-based approach for removal of various MRI artifacts. THEORY: Recently, the annihilating filter based low-rank Hankel matrix approach was proposed. The annihilating filter based low-rank Hankel matrix exploits the duality between the low-rankness of weighted Hankel structured matrix and the sparsity of signal in a transform domain. Because MR artifacts usually appeared as sparse k-space components, the low-rank Hankel matrix from underlying artifact-free k-space data can be exploited to decompose the sparse outliers. METHODS: The sparse + low-rank decomposition framework using Hankel matrix was proposed for removal of MRI artifacts. Alternating direction method of multipliers algorithm was employed for the minimization of associated cost function with the initialized matrices from a factorization-based matrix completion. RESULTS: Experimental results demonstrated that the proposed algorithm can correct MR artifacts including herringbone (crisscross), motion, and zipper artifacts without image distortion. CONCLUSION: The proposed method may be a robust correction solution for various MRI artifacts that can be represented as sparse outliers. Magn Reson Med 78:327-340, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Beyond Born-Rytov limit for super-resolution optical diffraction tomography.

Optical diffraction tomography (ODT) using Born or Rytov approximation suffers from severe distortions in reconstructed refractive index (RI) tomograms when multiple scattering occurs or the scattering signals are strong. These effects are usually seen as a significant impediment to the application of ODT because multiple scattering is directly linked to an unknown object itself rather than a surrounding medium, and a strong scatter invalidates the underlying assumptions of the Born and Rytov approximations. The focus of this article is to demonstrate for the first time that multiple scattering and high material contrast, if handled aptly, can significantly improve the image quality of the ODT thanks to multiple scattering inside a sample. Experimental verification using various phantom and biological cells substantiates that we not only revealed the structures that were not observable using the conventional approaches but also resolved the long-standing problem of missing cones in the ODT.

Translational motion correction algorithm for truncated cone-beam CT using opposite projections.

BACKGROUND: Cone-beam computed tomography (CBCT) is widely used in various medical imaging applications, including dental examinations. Dental CBCT images often suffer from motion artifacts caused by involuntary rigid motion of patients. However, earlier motion compensation studies are not applicable for dental CBCT systems using truncated detectors. OBJECTIVE: This study proposes a novel motion correction algorithm that can be applied for truncated dental CBCT images. METHODS: We propose a two-step method for motion correction. First, we estimate the relative displacement of each pair of opposite projections by finding the motion vector that maximizes the two-dimensional correlation coefficients of the opposite projections. Second, we convert the relative displacement into the absolute coordinate motion that yields the highest image sharpness of the reconstruction image. Using the motion vectors in the absolute coordinate system, motion artifacts are then compensated by modifying the trajectory of the source and detector during the back-projection step of the image reconstruction process. RESULTS: In simulation, the proposed method successfully estimated the true relative displacement. After converting to the absolute coordinate motions, the motion-compensated image was close to the ground-truth image and exhibited a lower mean-square-error than that of the uncompensated image. The results from the real data experiment also confirmed that the proposed method successfully compensated for the motion artifacts. CONCLUSIONS: The experimental results confirmed that the proposed method was applicable to most dental CBCT systems using a truncated detector without any use of an additional motion tracking system nor prior knowledge.

Sparse SPM: Group Sparse-dictionary learning in SPM framework for resting-state functional connectivity MRI analysis.

Recent studies of functional connectivity MR imaging have revealed that the default-mode network activity is disrupted in diseases such as Alzheimer's disease (AD). However, there is not yet a consensus on the preferred method for resting-state analysis. Because the brain is reported to have complex interconnected networks according to graph theoretical analysis, the independency assumption, as in the popular independent component analysis (ICA) approach, often does not hold. Here, rather than using the independency assumption, we present a new statistical parameter mapping (SPM)-type analysis method based on a sparse graph model where temporal dynamics at each voxel position are described as a sparse combination of global brain dynamics. In particular, a new concept of a spatially adaptive design matrix has been proposed to represent local connectivity that shares the same temporal dynamics. If we further assume that local network structures within a group are similar, the estimation problem of global and local dynamics can be solved using sparse dictionary learning for the concatenated temporal data across subjects. Moreover, under the homoscedasticity variance assumption across subjects and groups that is often used in SPM analysis, the aforementioned individual and group analyses using sparse dictionary learning can be accurately modeled by a mixed-effect model, which also facilitates a standard SPM-type group-level inference using summary statistics. Using an extensive resting fMRI data set obtained from normal, mild cognitive impairment (MCI), and Alzheimer's disease patient groups, we demonstrated that the changes in the default mode network extracted by the proposed method are more closely correlated with the progression of Alzheimer's disease.

Reference-free single-pass EPI Nyquist ghost correction using annihilating filter-based low rank Hankel matrix (ALOHA).

PURPOSE: MR measurements from an echo-planar imaging (EPI) sequence produce Nyquist ghost artifacts that originate from inconsistencies between odd and even echoes. Several reconstruction algorithms have been proposed to reduce such artifacts, but most of these methods require either additional reference scans or multipass EPI acquisition. This article proposes a novel and accurate single-pass EPI ghost artifact correction method that does not require any additional reference data. THEORY AND METHODS: After converting a ghost correction problem into separate k-space data interpolation problems for even and odd phase encoding, our algorithm exploits an observation that the differential k-space data between the even and odd echoes is a Fourier transform of an underlying sparse image. Accordingly, we can construct a rank-deficient Hankel structured matrix, whose missing data can be recovered using an annihilating filter-based low rank Hankel structured matrix completion approach. RESULTS: The proposed method was applied to EPI data for both single and multicoil acquisitions. Experimental results using in vivo data confirmed that the proposed method can completely remove ghost artifacts successfully without prescan echoes. CONCLUSION: Owing to the discovery of the annihilating filter relationship from the intrinsic EPI image property, the proposed method successfully suppresses ghost artifacts without a prescan step. Magn Reson Med 76:1775-1789, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Acceleration of MR parameter mapping using annihilating filter-based low rank hankel matrix (ALOHA).

PURPOSE: MR parameter mapping is one of clinically valuable MR imaging techniques. However, increased scan time makes it difficult for routine clinical use. This article aims at developing an accelerated MR parameter mapping technique using annihilating filter based low-rank Hankel matrix approach (ALOHA). THEORY: When a dynamic sequence can be sparsified using spatial wavelet and temporal Fourier transform, this results in a rank-deficient Hankel structured matrix that is constructed using weighted k-t measurements. ALOHA then utilizes the low rank matrix completion algorithm combined with a multiscale pyramidal decomposition to estimate the missing k-space data. METHODS: Spin-echo inversion recovery and multiecho spin echo pulse sequences for T1 and T2 mapping, respectively, were redesigned to perform undersampling along the phase encoding direction according to Gaussian distribution. The missing k-space is reconstructed using ALOHA. Then, the parameter maps were constructed using nonlinear regression. RESULTS: Experimental results confirmed that ALOHA outperformed the existing compressed sensing algorithms. Compared with the existing methods, the reconstruction errors appeared scattered throughout the entire images rather than exhibiting systematic distortion along edges and the parameter maps. CONCLUSION: Given that many diagnostic errors are caused by the systematic distortion of images, ALOHA may have a great potential for clinical applications. Magn Reson Med 76:1848-1864, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Whole-brain perfusion imaging with balanced steady-state free precession arterial spin labeling.

Recently, balanced steady-state free precession (bSSFP) readout has been proposed for arterial spin labeling (ASL) perfusion imaging to reduce susceptibility artifacts at a relatively high spatial resolution and signal-to-noise ratio (SNR). However, the main limitation of bSSFP-ASL is the low spatial coverage. In this work, methods to increase the spatial coverage of bSSFP-ASL are proposed for distortion-free, high-resolution, whole-brain perfusion imaging. Three strategies of (i) segmentation, (ii) compressed sensing (CS) and (iii) a hybrid approach combining the two methods were tested to increase the spatial coverage of pseudo-continuous ASL (pCASL) with three-dimensional bSSFP readout. The spatial coverage was increased by factors of two, four and six using each of the three approaches, whilst maintaining the same total scan time (5.3 min). The number of segments and/or CS acceleration rate (R) correspondingly increased to maintain the same bSSFP readout time (1.2 s). The segmentation approach allowed whole-brain perfusion imaging for pCASL-bSSFP with no penalty in SNR and/or total scan time. The CS approach increased the spatial coverage of pCASL-bSSFP whilst maintaining the temporal resolution, with minimal impact on the image quality. The hybrid approach provided compromised effects between the two methods. Balanced SSFP-based ASL allows the acquisition of perfusion images with wide spatial coverage, high spatial resolution and SNR, and reduced susceptibility artifacts, and thus may become a good choice for clinical and neurological studies. Copyright © 2015 John Wiley & Sons, Ltd.

Comparative study of iterative reconstruction algorithms for missing cone problems in optical diffraction tomography.

In optical tomography, there exist certain spatial frequency components that cannot be measured due to the limited projection angles imposed by the numerical aperture of objective lenses. This limitation, often called as the missing cone problem, causes the under-estimation of refractive index (RI) values in tomograms and results in severe elongations of RI distributions along the optical axis. To address this missing cone problem, several iterative reconstruction algorithms have been introduced exploiting prior knowledge such as positivity in RI differences or edges of samples. In this paper, various existing iterative reconstruction algorithms are systematically compared for mitigating the missing cone problem in optical diffraction tomography. In particular, three representative regularization schemes, edge preserving, total variation regularization, and the Gerchberg-Papoulis algorithm, were numerically and experimentally evaluated using spherical beads as well as real biological samples; human red blood cells and hepatocyte cells. Our work will provide important guidelines for choosing the appropriate regularization in ODT.

High-speed terahertz reflection three-dimensional imaging using beam steering.

High-speed terahertz (THz) reflection three-dimensional (3D) imaging is demonstrated using electronically-controlled optical sampling (ECOPS) and beam steering. ECOPS measurement is used for scanning an axial range of 7.8 mm in free space at 1 kHz scan rate while a transverse range of 100 × 100 mm(2) is scanned using beam steering instead of moving an imaging target. Telecentric f-θ lenses with axial and non-axial symmetry have been developed for beam steering. It is experimentally demonstrated that the non-axially symmetric lens has better characteristics than the axially symmetric lens. The total scan time depends on the number of points in a transverse range. For example, it takes 40 s for 200 × 200 points and 10 s for 100 × 100 points. To demonstrate the application of the imaging technique to nondestructive testing, THz 3D tomographic images of a glass fiber reinforced polymer sample with artificial internal defects have been acquired using the lenses for comparison.