Integrated platform for multiscale molecular imaging and phenotyping of the human brain.

Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multiscale details of individual cells and their connectivity in the human organ-scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells from the same human brain. The platform includes three core elements: a vibrating microtome for ultraprecision slicing of large-scale tissues without losing cellular connectivity (MEGAtome), a polymer hydrogel-based tissue processing technology for multiplexed multiscale imaging of human organ-scale tissues (mELAST), and a computational pipeline for reconstructing three-dimensional connectivity across multiple brain slabs (UNSLICE). We applied this platform for analyzing human Alzheimer's disease pathology at multiple scales and demonstrating scalable neural connectivity mapping in the human brain.

Transfer Learning-Based B-Line Assessment of Lung Ultrasound for Acute Heart Failure.

OBJECTIVE: B-lines assessed by lung ultrasound (LUS) outperform physical exam, chest radiograph, and biomarkers for the associated diagnosis of acute heart failure (AHF) in the emergent setting. The use of LUS is however limited to trained professionals and suffers from interpretation variability. The objective was to utilize transfer learning to create an AI-enabled software that can aid novice users to automate LUS B-line interpretation. METHODS: Data from an observational AHF LUS study provided standardized cine clips for AI model development and evaluation. A total of 49,952 LUS frames from 30 patients were hand scored and trained on a convolutional neural network (CNN) to interpret B-lines at the frame level. A random independent evaluation set of 476 LUS clips from 60 unique patients assessed model performance. The AI models scored the clips on both a binary and ordinal 0-4 multiclass assessment. RESULTS: A multiclassification AI algorithm had the best performance at the binary level when applied to the independent evaluation set, AUC of 0.967 (95% CI 0.965-0.970) for detecting pathologic conditions. When compared to expert blinded reviewer, the 0-4 multiclassification AI algorithm scale had a reported linear weighted kappa of 0.839 (95% CI 0.804-0.871). CONCLUSIONS: The multiclassification AI algorithm is a robust and well performing model at both binary and ordinal multiclass B-line evaluation. This algorithm has the potential to be integrated into clinical workflows to assist users with quantitative and objective B-line assessment for evaluation of AHF.

Individualized Ultrasound-Guided Intervention Phantom Development, Fabrication, and Proof of Concept.

Commercial ultrasound vascular phantoms lack the anatomic diversity required for robust pre-clinical interventional device testing. We fabricated individualized phantoms to test an artificial intelligence enabled ultrasound-guided surgical robotic system (AI-GUIDE) which allows novices to cannulate deep vessels. After segmenting vessels on computed tomography scans, vessel cores, bony anatomy, and a mold tailored to the skin contour were 3D-printed. Vessel cores were coated in silicone, surrounded in tissue-mimicking gel tailored for ultrasound and needle insertion, and dissolved with water. One upper arm and four inguinal phantoms were constructed. Operators used AI-GUIDE to deploy needles into phantom vessels. Two groin phantoms were tested due to imaging artifacts in the other two phantoms. Six operators (medical experience: none, 3; 1-5 years, 2; 5+ years, 1) inserted 27 inguinal needles with 81% (22/27) success in a median of 48 seconds. Seven operators performed 24 arm injections, without tuning the AI for arm anatomy, with 71% (17/24) success. After excluding failures due to motor malfunction and a defective needle, success rate was 100% (22/22) in the groin and 85% (17/20) in the arm. Individualized 3D-printed phantoms permit testing of surgical robotics across a large number of operators and different anatomic sites. AI-GUIDE operators rapidly and reliably inserted a needle into target vessels in the upper arm and groin, even without prior medical training. Virtual device trials in individualized 3-D printed phantoms may improve rigor of results and expedite translation.Clinical Relevance- Individualized phantoms enable rigorous and efficient evaluation of interventional devices and reduce the need for animal and human subject testing.

Axon Tracing and Centerline Detection using Topologically-Aware 3D U-Nets.

As advances in microscopy imaging provide an ever clearer window into the human brain, accurate reconstruction of neural connectivity can yield valuable insight into the relationship between brain structure and function. However, human manual tracing is a slow and laborious task, and requires domain expertise. Automated methods are thus needed to enable rapid and accurate analysis at scale. In this paper, we explored deep neural networks for dense axon tracing and incorporated axon topological information into the loss function with a goal to improve the performance on both voxel-based segmentation and axon centerline detection. We evaluated three approaches using a modified 3D U-Net architecture trained on a mouse brain dataset imaged with light sheet microscopy and achieved a 10% increase in axon tracing accuracy over previous methods. Furthermore, the addition of centerline awareness in the loss function outperformed the baseline approach across all metrics, including a boost in Rand Index by 8%.

Transfer Learning for Automated COVID-19 B-Line Classification in Lung Ultrasound.

Lung ultrasound (LUS) as a diagnostic tool is gaining support for its role in the diagnosis and management of COVID-19 and a number of other lung pathologies. B-lines are a predominant feature in COVID-19, however LUS requires a skilled clinician to interpret findings. To facilitate the interpretation, our main objective was to develop automated methods to classify B-lines as pathologic vs. normal. We developed transfer learning models based on ResNet networks to classify B-lines as pathologic (at least 3 B-lines per lung field) vs. normal using COVID-19 LUS data. Assessment of B-line severity on a 0-4 multi-class scale was also explored. For binary B-line classification, at the frame-level, all ResNet models pretrained with ImageNet yielded higher performance than the baseline nonpretrained ResNet-18. Pretrained ResNet-18 has the best Equal Error Rate (EER) of 9.1% vs the baseline of 11.9%. At the clip-level, all pretrained network models resulted in better Cohen's kappa agreement (linear-weighted) and clip score accuracy, with the pretrained ResNet-18 having the best Cohen's kappa of 0.815 [95% CI: 0.804-0.826], and ResNet-101 the best clip scoring accuracy of 93.6%. Similar results were shown for multi-class scoring, where pretrained network models outperformed the baseline model. A class activation map is also presented to guide clinicians in interpreting LUS findings. Future work aims to further improve the multi-class assessment for severity of B-lines with a more diverse LUS dataset.

AI-Enabled, Ultrasound-Guided Handheld Robotic Device for Femoral Vascular Access.

Hemorrhage is a leading cause of trauma death, particularly in prehospital environments when evacuation is delayed. Obtaining central vascular access to a deep artery or vein is important for administration of emergency drugs and analgesics, and rapid replacement of blood volume, as well as invasive sensing and emerging life-saving interventions. However, central access is normally performed by highly experienced critical care physicians in a hospital setting. We developed a handheld AI-enabled interventional device, AI-GUIDE (Artificial Intelligence Guided Ultrasound Interventional Device), capable of directing users with no ultrasound or interventional expertise to catheterize a deep blood vessel, with an initial focus on the femoral vein. AI-GUIDE integrates with widely available commercial portable ultrasound systems and guides a user in ultrasound probe localization, venous puncture-point localization, and needle insertion. The system performs vascular puncture robotically and incorporates a preloaded guidewire to facilitate the Seldinger technique of catheter insertion. Results from tissue-mimicking phantom and porcine studies under normotensive and hypotensive conditions provide evidence of the technique's robustness, with key performance metrics in a live porcine model including: a mean time to acquire femoral vein insertion point of 53 ± 36 s (5 users with varying experience, in 20 trials), a total time to insert catheter of 80 ± 30 s (1 user, in 6 trials), and a mean number of 1.1 (normotensive, 39 trials) and 1.3 (hypotensive, 55 trials) needle insertion attempts (1 user). These performance metrics in a porcine model are consistent with those for experienced medical providers performing central vascular access on humans in a hospital.

A dual-stream deep convolutional network for reducing metal streak artifacts in CT images.

Machine learning and deep learning are rapidly finding applications in the medical imaging field. In this paper, we address the long-standing problem of metal artifacts in computed tomography (CT) images by training a dual-stream deep convolutional neural network for streak removal. While many metal artifact reduction methods exist, even state-of-the-art algorithms fall short in some clinical applications. Specifically, proton therapy planning requires high image quality with accurate tumor volumes to ensure treatment success. We explore a dual-stream deep network structure with residual learning to correct metal streak artifacts after a first-pass by a state-of-the-art interpolation-based algorithm, NMAR. We provide the network with a mask of the streaks in order to focus attention on those areas. Our experiments compare a mean squared error loss function with a perceptual loss function to emphasize preservation of image features and texture. Both visual and quantitative metrics are used to assess the resulting image quality for metal implant cases. Success may be due to the duality of information processing, with one network stream performing local structure correction, while the other stream provides an attention mechanism to destreak effectively. This study shows that image-domain deep learning can be highly effective for metal artifact reduction (MAR), and highlights the benefits and drawbacks of different loss functions for solving a major CT reconstruction challenge.

A new iterative algorithm for ring artifact reduction in CT using ring total variation.

PURPOSE: In computed tomography (CT), miscalibrated or imperfect detector elements produce stripe artifacts in the sinogram. The stripe artifacts in Radon space are responsible for concentric ring artifacts in the reconstructed images. In this work, a novel optimization model is proposed to remove the ring artifacts in an iterative reconstruction procedure. METHOD: In the proposed optimization model, a novel ring total variation (RTV) regularization is developed to penalize the ring artifacts in the image domain. Moreover, to correct the sinogram, a new correcting vector is proposed to compensate for malfunctioning of detectors in the projection domain. The optimization problem is solved by using the alternating minimization scheme (AMS). In each iteration, the fidelity term along with the RTV regularization is solved using the alternating direction method of multipliers (ADMM) to find the image, and then the correcting coefficient vector is updated for certain detectors according to the obtained image. Because the sinogram and the image are simultaneously updated, the proposed method basically performs in both image and sinogram domains. RESULTS: The proposed method is evaluated using both simulated and physical phantom datasets containing different ring artifact patterns. In the simulated datasets, the Shepp-Logan phantom, a real chest scan image and a noisy low-contrast phantom are considered for the performance evaluation of our method. We compare the quantitative root mean square error (RMSE) and structural similarity (SSIM) results of our algorithm with wavelet-Fourier sinogram filtering method by Munch et al., the ring artifact reduction method by Brun et al., and the TV-based ring correction method by Paleo and Mirone. Our proposed method is also evaluated using a physical phantom dataset where strong ring artifacts are manifest due to the miscalibration of a large number of detectors. Our proposed method outperforms the competing methods in terms of both qualitative and quantitative evaluation results. CONCLUSION: The experimental results in both simulated and physical phantom datasets show that the proposed method achieves the state-of-the-art ring artifact reduction performance in terms of RMSE, SSIM, and subjective visual quality.

Simultaneous Emission-Transmission Tomography in an MRI Hardware Framework.

Multi-modality imaging is essential for diagnosis and therapy in challenging cases. A Holy Grail of medical imaging is a hybrid imaging system combining computed tomography (CT), nuclear imaging, and magnetic resonance imaging (MRI) to deliver registered morphological, functional, and cellular/molecular information simultaneously and quantitatively for precision medicine. Recently, a unique imaging approach was demonstrated that combines nuclear imaging with polarized radiotracers and MRI-based spatial encoding. The detection scheme exploits the directional preference of γ-rays emitted from the polarized nuclei, and the result is a concentration image with resolution that can outperform standard nuclear imaging at a sensitivity significantly higher than that of MRI. However, the method does not calculate the attenuation image. Here we propose to obtain MRI-modulated γ-ray data for simultaneous image reconstruction of emission and transmission parameters, which could serve as a stepping stone toward simultaneous CT-SPECT-MRI. This method acquires synchronized datasets to provide insight into morphological features and molecular activities with accurate spatiotemporal registration. We present a complete overview of the system design and the formulation for tomographic reconstruction when the distribution of polarized radiotracers is either global or limited to a region of interest (ROI). Numerical results support the feasibility of our approach and suggest further research topics.

Structurally-sensitive Multi-scale Deep Neural Network for Low-Dose CT Denoising.

Computed tomography (CT) is a popular medical imaging modality and enjoys wide clinical applications. At the same time, the x-ray radiation dose associated with CT scannings raises a public concern due to its potential risks to the patients. Over the past years, major efforts have been dedicated to the development of Low-Dose CT (LDCT) methods. However, the radiation dose reduction compromises the signal-to-noise ratio (SNR), leading to strong noise and artifacts that downgrade CT image quality. In this paper, we propose a novel 3D noise reduction method, called Structurally-sensitive Multi-scale Generative Adversarial Net (SMGAN), to improve the LDCT image quality. Specifically, we incorporate three-dimensional (3D) volumetric information to improve the image quality. Also, different loss functions for training denoising models are investigated. Experiments show that the proposed method can effectively preserve structural and textural information in reference to normal-dose CT (NDCT) images, and significantly suppress noise and artifacts. Qualitative visual assessments by three experienced radiologists demonstrate that the proposed method retrieves more information, and outperforms competing methods.

Novel Detection Scheme for X-ray Small-Angle Scattering.

X-ray imaging techniques, including x-ray radiography and computed tomography, have been in use for decades and proven effective and indispensable in diagnosis and therapy due to their fine resolution and fast acquisition speed. However, the innate disadvantage of x-ray is the poor soft tissue contrast. Small-angle scattering signals were shown to provide unique information about the abnormality of soft tissues that is complementary to the traditional attenuation image. Currently, there is no effective small-angle scattering detection system. In this paper, we propose a new "collimation" design dedicated to capture a small-angle scattering radiographic image directly, which carries critical pathological information for differentiation between normal and abnormal tissues. Our design consists of two interlaced gratings so that both the primary flux and Compton scattering photons are effectively blocked to leave the apertures mainly open to small-angle scattering photons. Theoretical analysis and Monte Carlo simulations demonstrate that small-angle scattering radiography is feasible with our proposed technology.

Metal artifacts in computed tomography for radiation therapy planning: dosimetric effects and impact of metal artifact reduction.

A significant and increasing number of patients receiving radiation therapy present with metal objects close to, or even within, the treatment area, resulting in artifacts in computed tomography (CT) imaging, which is the most commonly used imaging method for treatment planning in radiation therapy. In the presence of metal implants, such as dental fillings in treatment of head-and-neck tumors, spinal stabilization implants in spinal or paraspinal treatment or hip replacements in prostate cancer treatments, the extreme photon absorption by the metal object leads to prominent image artifacts. Although current CT scanners include a series of correction steps for beam hardening, scattered radiation and noisy measurements, when metal implants exist within or close to the treatment area, these corrections do not suffice. CT metal artifacts affect negatively the treatment planning of radiation therapy either by causing difficulties to delineate the target volume or by reducing the dose calculation accuracy. Various metal artifact reduction (MAR) methods have been explored in terms of improvement of organ delineation and dose calculation in radiation therapy treatment planning, depending on the type of radiation treatment and location of the metal implant and treatment site. Including a brief description of the available CT MAR methods that have been applied in radiation therapy, this article attempts to provide a comprehensive review on the dosimetric effect of the presence of CT metal artifacts in treatment planning, as reported in the literature, and the potential improvement suggested by different MAR approaches. The impact of artifacts on the treatment planning and delivery accuracy is discussed in the context of different modalities, such as photon external beam, brachytherapy and particle therapy, as well as by type and location of metal implants.

Vision 20/20: Simultaneous CT-MRI--Next chapter of multimodality imaging.

Multimodality imaging systems such as positron emission tomography-computed tomography (PET-CT) and MRI-PET are widely available, but a simultaneous CT-MRI instrument has not been developed. Synergies between independent modalities, e.g., CT, MRI, and PET/SPECT can be realized with image registration, but such postprocessing suffers from registration errors that can be avoided with synchronized data acquisition. The clinical potential of simultaneous CT-MRI is significant, especially in cardiovascular and oncologic applications where studies of the vulnerable plaque, response to cancer therapy, and kinetic and dynamic mechanisms of targeted agents are limited by current imaging technologies. The rationale, feasibility, and realization of simultaneous CT-MRI are described in this perspective paper. The enabling technologies include interior tomography, unique gantry designs, open magnet and RF sequences, and source and detector adaptation. Based on the experience with PET-CT, PET-MRI, and MRI-LINAC instrumentation where hardware innovation and performance optimization were instrumental to construct commercial systems, the authors provide top-level concepts for simultaneous CT-MRI to meet clinical requirements and new challenges. Simultaneous CT-MRI fills a major gap of modality coupling and represents a key step toward the so-called "omnitomography" defined as the integration of all relevant imaging modalities for systems biology and precision medicine.

Semiautomatic volumetric tumor segmentation for hepatocellular carcinoma: comparison between C-arm cone beam computed tomography and MRI.

RATIONALE AND OBJECTIVES: To evaluate the precision and reproducibility of a semiautomatic tumor segmentation software in measuring tumor volume of hepatocellular carcinoma (HCC) before the first transarterial chemo-embolization (TACE) on contrast-enhancement magnetic resonance imaging (CE-MRI) and intraprocedural dual-phase C-arm cone beam computed tomography (DP-CBCT) images. MATERIALS AND METHODS: Nineteen HCCs were targeted in 19 patients (one per patient) who underwent baseline diagnostic CE-MRI and an intraprocedural DP-CBCT. The images were obtained from CE-MRI (arterial phase of an intravenous contrast medium injection) and DP-CBCT (delayed phase of an intra-arterial contrast medium injection) before the actual embolization. Three readers measured tumor volumes using a semiautomatic three-dimensional volumetric segmentation software that used a region-growing method employing non-Euclidean radial basis functions. Segmentation time and spatial position were recorded. The tumor volume measurements between image sets were compared using linear regression and Student's t-test, and evaluated with intraclass-correlation analysis (ICC). The inter-rater Dice similarity coefficient (DSC) assessed the segmentation spatial localization. RESULTS: All 19 HCCs were analyzed. On CE-MRI and DP-CBCT examinations, respectively, 1) the mean segmented tumor volumes were 87 ± 8 cm(3) (2-873) and 92 ± 10 cm(3) (1-954), with no statistical difference of segmented volumes by readers of each tumor between the two imaging modalities and the mean time required for segmentation was 66 ± 45 seconds (21-173) and 85 ± 34 seconds (17-214) (P = .19); 2) the ICCs were 0.99 and 0.974, showing a strong correlation among readers; and 3) the inter-rater DSCs showed a good to excellent inter-user agreement on the spatial localization of the tumor segmentation (0.70 ± 0.07 and 0.74 ± 0.05, P = .07). CONCLUSION: This study shows a strong correlation, a high precision, and excellent reproducibility of semiautomatic tumor segmentation software in measuring tumor volume on CE-MRI and DP-CBCT images. The use of the segmentation software on DP-CBCT and CE-MRI can be a valuable and highly accurate tool to measure the volume of hepatic tumors.