Multimodal Imaging Applications Research Articles

A fast blind zero-shot denoiser

Image noise is a common problem in light microscopy. This is particularly true in real-time live-cell imaging applications in which long-term cell viability necessitates low-light conditions. Modern denoisers are typically trained on a representative dataset, sometimes consisting of just unpaired noisy shots. However, when data are acquired in real time to track dynamic cellular processes, it is not always practical nor economical to generate these training sets. Recently, denoisers have emerged that allow us to denoise single images without a training set or knowledge about the underlying noise. But such methods are currently too slow to be integrated into imaging pipelines that require rapid, real-time hardware feedback. Here we present Noise2Fast, which can overcome these limitations. Noise2Fast uses a novel downsampling technique we refer to as ‘chequerboard downsampling’. This allows us to train on a discrete 4-image training set, while convergence can be monitored using the original noisy image. We show that Noise2Fast is faster than all similar methods with only a small drop in accuracy compared to the gold standard. We integrate Noise2Fast into real-time multi-modal imaging applications and demonstrate its broad applicability to diverse imaging and analysis pipelines.

Multi-Modality Cardiac Imaging for Pericardial Diseases: A Contemporary Review.

Advances in multi-modality cardiac imaging have aided the evaluation, surveillance and treatment guidance of pericardial diseases, which have traditionally been a challenging group of conditions to manage. Although echocardiography remains the first-line imaging modality to assess the pericardium, both computed tomography (CT) and magnetic resonance imaging (MRI) have valuable complimentary roles. It is critical for clinicians to have a clear understanding of the utilities, advantages and disadvantages of these cardiac imaging modalities in pericardial pathologies. This contemporary review provides an update regarding the applications of multi-modality cardiac imaging in the evaluation of pericardial syndromes including acute/recurrent pericarditis, effusion/tamponade, constriction, masses and congenital anomalies.

Preprocedural Multimodality Imaging in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with increased risk of heart failure, stroke, and death. In current medical practice, multimodality imaging is routinely used in the management of AF. Twenty-one years ago, the ACUTE trial (Assessment of Cardioversion Using Transesophageal Echocardiography) results were published, and the management of AF changed forever by incorporating transesophageal echocardiography guided cardioversion of patients in AF for the first time. Current applications of multimodality imaging in AF in 2022 include the use of transesophageal echocardiography and computed tomography before cardioversion to exclude left atrial thrombus and in left atrial appendage occlusion device implantation. Transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance are clinically used for AF ablation planning. The decision to use a particular imaging modality in AF is based on patient's characteristics, guideline recommendation, institutional preferences, expertise, and cost. In this first of 2-part review series, we discuss the preprocedural role of echocardiography, computed tomography, and cardiac magnetic resonance in the AF, with regard to their clinical applications, relevant outcomes data and unmet needs, and highlights future directions in this rapidly evolving field.

Multimodal ultrasound imaging: A method to improve the accuracy of diagnosing thyroid TI-RADS 4 nodules.

Thyroid nodule is a common and frequently occurring disease in the neck in recent years, and ultrasound has become the preferred imaging diagnosis method for thyroid nodule due to its advantages of noninvasive, nonradiation, real-time, and repeatable. The thyroid imaging, reporting and data system (TI-RADS) classification standard scores suspicious nodules that are difficult to determine benign and malignant as grade 4, and further pathological puncture is recommended clinically, which may lead to a large number of unnecessary biopsies and operations. Including conventional ultrasound, ACR TI-RADS, shear wave elastography, super microvascular imaging, contrast enhanced ultrasound, "firefly," artificial intelligence, and multimodal ultrasound imaging used in combination. In order to identify the most clinically significant malignant tumors when reducing invasive operations. This article reviews the application and research progress of multimodal ultrasound imaging in the diagnosis of TI-RADS 4 thyroid nodules.

A Multimodality Myocardial Perfusion Phantom: Initial Quantitative Imaging Results.

This proof-of-concept study explores the multimodal application of a dedicated cardiac flow phantom for ground truth contrast measurements in dynamic myocardial perfusion imaging with CT, PET/CT, and MRI. A 3D-printed cardiac flow phantom and flow circuit mimics the shape of the left ventricular cavity (LVC) and three myocardial regions. The regions are filled with tissue-mimicking materials and the flow circuit regulates and measures contrast flow through LVC and myocardial regions. Normal tissue perfusion and perfusion deficits were simulated. Phantom measurements in PET/CT, CT, and MRI were evaluated with clinically used hardware and software. The reference arterial input flow was 4.0 L/min and myocardial flow 80 mL/min, corresponding to myocardial blood flow (MBF) of 1.6 mL/g/min. The phantom demonstrated successful completion of all processes involved in quantitative, multimodal myocardial perfusion imaging (MPI) applications. Contrast kinetics in time intensity curves were in line with expectations for a mimicked perfusion deficit (38 s vs. 32 s in normal tissue). Derived MBF in PET/CT and CT led to under- and overestimation of reference flow of 0.9 mL/g/min and 4.5 mL/g/min, respectively. Simulated perfusion deficit (0.8 mL/g/min) in CT resulted in MBF of 2.8 mL/g/min. We successfully performed initial, quantitative perfusion measurements with a dedicated phantom setup utilizing clinical hardware and software. These results showcase the multimodal phantom’s potential.

A Case Report on Application of Multimodal Imaging to an Alcoholic Cardiomyopathic Patient Undergoing Heart Transplantation

Alcoholic cardiomyopathy (ACM) is a dilated cardiomyopathy induced by excessive alcohol consumption that causes progressive cardiac dysfunction and chamber dilatation, leading to arrhythmias, heart failure, and death. Cardiac transplantation is the final measure for end-stage ACM. In this case, we used multimodal imaging for ACM diagnosis in a patient with refractory heart failure. The patient received a heart transplant with a good prognosis, and his pathological results after the transplant confirmed our suspected diagnosis. End-stage ACM may lead to refractory heart failure and multimodal imaging may play an important role in the diagnosis, prognosis prediction, and follow-up study of suspected ACM.

Cerebrovascular Events after Transcatheter Aortic Valve Replacement: The Difficulty in Predicting the Unpredictable.

Background: Cerebrovascular events (CVE) are feared complications following transcatheter aortic valve replacement (TAVR). We aimed to develop a new risk model for CVE prediction with the application of multimodal imaging. Methods: From May 2011 to August 2019, a total of 2015 patients underwent TAVR at our institution. The study cohort was subdivided into a derivation cohort (n = 1365) and a validation cohort (n = 650) for risk model development. Results: Of 2015 patients, 72 (3.6%) developed TAVR-related CVE. Pre-procedural factors of our risk model were history of prior CVE, a larger aortic valve area (≥0.55 cm2), a large aortic angulation (≥48.5°), and enhanced calcification of the right coronary cusp (≥447.2 AU), left ventricular outflow tract (≥262.4 AU), and ascending thoracic aorta (≥116.4 AU). Our risk model was superior for in-hospital CVE prediction following TAVR in the establishment cohort (AUC 0.73, 95% CI 0.66–0.80; p < 0.001) compared to other risk scores, such as the EuroSCORE II or the CHA2DS2-VASc score. Conclusions: Although CVE prediction in patients undergoing TAVR is challenging due to the complex nature of the TAVR procedure, our study highlights that multimodal imaging is a promising approach to generate a more accurate risk model for CVE prediction.

Abstract 2485: Applications of multimodality ex-vivo tissue imaging to improve breast cancer diagnosis and treatment

Abstract Breast cancer is the most common malignancy affecting women worldwide. Existing models being used to study breast cancer include the Patient-Derived Tumor Organoid (PDTO) Model and the Patient-Derived Tumor Xenograft (PDTX) Model. Both models involve the surgical removal of a tumor from a patient which then undergoes processing to grow an organoid or injected into mice to test different therapies outside the body. However, these models not only take a considerable amount of time to develop properly, but in many cases aren’t representative of the most aggressive tumor cells present within a heterogeneous tissue sample in order to draw the most clinically accurate conclusions of a tumor's response to therapy. In order to advance clinical research, more efficient culture systems that are faster growing and more representative of biological characteristics in-vivo are needed. Previous work from the Karczmar Lab discovered that high-resolution magnetic resonance imaging (MRI) can detect regions of aggressive cancer in biopsy specimens from mouse models, and give additional information on characteristics including cell density, tissue composition, and cancer stage. With this recent discovery, it is hypothesized that ex-vivo imaging could be used to identify aggressive tumor cells in human heterogeneous breast cancer tissue samples to produce higher quality and faster-growing models for testing new therapies and guiding individual patient therapy for breast cancer. The primary aim for this study was to specifically identify image-based markers for regions of aggressive cancer by comparing ex-vivo high-resolution MRI with histology and immunohistochemistry in 3D. Distant normal (DN) and tumor (Tu) tissue samples from breast cancer patients were obtained and imaged using T2-weighted 3D Rapid Imaging with Refocused Echoes (RARE) and stained using hematoxylin and eosin (H&amp;E), commonly used by pathologists to diagnose cancers. Then, the ex-vivo T2-weighted 3D RARE images were correlated to the histopathological H&amp;E staining and confirmed by breast radiologists and pathologists. Preliminary results revealed that high-resolution MR imaging detects mammary glands, ducts, and white adipose tissue in DN tissue samples and regions of invasive cancer, including ductal carcinoma in-situ (DCIS) and necrosis, in Tu tissue. Based on these results, aggressive cancer regions were proven to be identified using image-based guidance and potentially be extracted using core-needle biopsy to improve PDTO and PDTX models for studying breast cancer and advancing individual patient therapy. Citation Format: Corazon Avila, Gregory Karczmar, Devkumar Mustafi. Applications of multimodality ex-vivo tissue imaging to improve breast cancer diagnosis and treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2485.

Amino-modified-silica-coated gadolinium-copper nanoclusters, conjugated to AS1411 aptamer and radiolabeled with technetium-99 m as a novel multimodal imaging agent

Hybridimagingtechnology has the potential to provide reliable imagingand accurate detection of cancer cells by combining the advantages and overcoming the shortages of various clinical imaging tools. Nanomaterials with unique targeting properties and their small size have improved biomedical imaging. Indeed, their small size determines local contrast agent concentrations in tumors by enhanced permeability and retention (EPR) effect. In this work, amino-modified silica-coated Gadolinium-Copper Nanoclusters were fabricated and conjugated to AS1411 aptamer (Apt-ASGCuNCs) and radiolabeled with technetium-99 m (99mTc) for in vivo fluorescence imaging, magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). The synthesized nanoconjugate was fully characterized by transmission electron microscopy (TEM), element mapping, fluorescence spectroscopy, and Fourier-transform infrared spectroscopy. Moreover, XTT assay, and apoptosis and necrosis methods were applied to study toxicity. Radiochemical yield was calculated 93% that revealed a great potential for complex formation between Apt-ASGCuNCs and 99mTcO4−. Also, good stability of 99mTc-Apt-ASGCuNCs was found in the human serum up to 4 h. Both Apt-ASGCuNCs and 99mTc-Apt-ASGCuNCs indicated a considerable tumor-targeting in in vivo fluorescence imaging, MRI and SPECT with 4T1 tumor-bearing BALB/c mice. The biodistribution results showed no undesirable accumulation of 99mTc-Apt-ASGCuNCs in the liver, and spleen as it circulated freely in the blood pool. Meanwhile, 99mTc-Apt-ASGCuNCs were removed from the body through the renal clearance system, making it more convenient for future multimodality imaging applications.

Coupled Hydrodynamic Flow Focusing (cHFF) to Engineer Lipid-Polymer Nanoparticles (LiPoNs) for Multimodal Imaging and Theranostic Applications.

An optimal design of nanocarriers is required to overcome the gap between synthetic and biological identity, improving the clinical translation of nanomedicine. A new generation of hybrid vehicles based on lipid–polymer coupling, obtained by Microfluidics, is proposed and validated for theranostics and multimodal imaging applications. A coupled Hydrodynamic Flow Focusing (cHFF) is exploited to control the time scales of solvent exchange and the coupling of the polymer nanoprecipitation with the lipid self-assembly simultaneously, guiding the formation of Lipid–Polymer NPs (LiPoNs). This hybrid lipid–polymeric tool is made up of core–shell structure, where a polymeric chitosan core is enveloped in a lipid bilayer, capable of co-encapsulating simultaneously Gd-DTPA and Irinotecan/Atto 633 compounds. As a result, a monodisperse population of hybrid NPs with an average size of 77 nm, with preserved structural integrity in different environmental conditions and high biocompatibility, can be used for MRI and Optical applications. Furthermore, preliminary results show the enhanced delivery and therapeutic efficacy of Irinotecan-loaded hybrid formulation against U87 MG cancers cells.

Application of multimodal imaging in the diagnosis of intrahepatic splenosis: Two case reports and a literature review

Intrahepatic splenosis is quite rare and is often misdiagnosed as other lesions. We present two cases of intrahepatic splenosis examined with hepatobiliary contrast agents, intravoxel incoherent motion diffusion-weighted imaging and magnetic resonance elastography. We discuss various imaging modalities and the roles of various magnetic resonance imaging methods in diagnosis. We also discuss the differentiating features that allow the correct diagnosis to be made and provide a brief review of the literature.

Advances in Surface Enhanced Raman Spectroscopy for in Vivo Imaging in Oncology.

In the last two decades, the application of surface enhanced Raman scattering (SERS) nanoparticles for preclinical cancer imaging has attracted increasing attention. Raman imaging with SERS nanoparticles offers unparalleled sensitivity, providing a platform for molecular targeting, and granting multiplexed and multimodal imaging capabilities. Recent progress has been facilitated not only by the optimization of the SERS contrast agents themselves, but also by the developments in Raman imaging approaches and instrumentation. In this article, we review the principles of Raman scattering and SERS, present advances in Raman instrumentation specific to cancer imaging, and discuss the biological means of ensuring selective in vivo uptake of SERS contrast agents for targeted, multiplexed, and multimodal imaging applications. We offer our perspective on areas that must be addressed in order to facilitate the clinical translation of SERS contrast agents for in vivo imaging in oncology.

Application of Multimodal Magnetic Resonance Imaging in Green Channel of Acute and Hyperacute Ischemic Stroke.

The purpose of this study was to observe the effects of multimodal magnetic resonance imaging (MRI) in the green channel of acute and hyperacute ischemic strokes, in order to better guide clinical treatment. The clinical data of 126 patients with acute and hyperacute ischemic stroke who received interventional treatment in the emergency green channel was collected retrospectively. The patients who received multimodal computed tomography (CT) were included in the CT group. Patients who underwent multimodal MRI examinations were included in the MRI group, and the door-to-needle time (DNT), neurological function, and prognosis of the two groups were compared. The result turned out that among the 126 patients included, 40 patients underwent CT examination (CT group) and 86 patients underwent MRI examination (MRI group). A comparison of general data between the CT group and the MRI group showed P > 0.05. The MRI group's DNT time (61.23 ± 9.32) min was shorter than that of the CT group (87.22 ± 14.26) min, P < 0.05. Through comparison, the P values of mRS scores and NIHSS scores in both groups were greater than 0.05. After treatment, the mRS score and NIHSS score of the MRI group was lower, with P < 0.05. According to the results of this study, it can be concluded that emergency multimodal MRI could shorten the DNT time of patients with acute and hyperacute ischemic stroke, reduce the degree of neurological impairment, and improve the prognosis.

Mask-Guided Spatial–Temporal Graph Neural Network for Multifrequency Electrical Impedance Tomography

Multi-frequency Electrical Impedance Tomography (mfEIT) is an emerging biomedical imaging modality that exploits frequency-dependent electrical properties. The mfEIT-image-reconstruction problem for cell imaging is particularly challenging due to weak signals from miniaturized sensors and high sensitivity to modelling errors. Existing approaches are primarily based on the linearized model and few are applied to the miniaturized setup. Here we report a Mask-guided Spatial-Temporal Graph Neural Network (M-STGNN) to reconstruct mfEIT images in cell culture imaging. The M-STGNN captures simultaneously spatial and frequency correlations, and the spatial correlation is further constrained by geometric structures from auxiliary binary masks, such as CT or microscopic images. We validate the mfEIT approach through numerical simulations and experiments on MCF-7 human breast cancer cell aggregates. The results demonstrate the superiority of M-STGNN over the state of the art with an improvement of approximately 10.7% under the experimental setup. It can be readily extended to multi-modal biomedical imaging applications.

Applications of multimodality imaging for left atrial catheter ablation.

Atrial arrhythmias, including atrial fibrillation and atrial flutter, may be treated through catheter ablation. The process of atrial arrhythmia catheter ablation, which includes patient selection, pre-procedural planning, intra-procedural guidance, and post-procedural assessment, is typically characterized by the use of several imaging modalities to sequentially inform key clinical decisions. Increasingly, advanced imaging modalities are processed via specialized image analysis techniques and combined with intra-procedural electrical measurements to inform treatment approaches. Here, we review the use of multimodality imaging for left atrial ablation procedures. The article first outlines how imaging modalities are routinely used in the peri-ablation period. We then describe how advanced imaging techniques may inform patient selection for ablation and ablation targets themselves. Ongoing research directions for improving catheter ablation outcomes by using imaging combined with advanced analyses for personalization of ablation targets are discussed, together with approaches for their integration in the standard clinical environment. Finally, we describe future research areas with the potential to improve catheter ablation outcomes.

Tuning of Hydrogel Architectures by Ionotropic Gelation in Microfluidics: Beyond Batch Processing to Multimodal Diagnostics.

Microfluidics is emerging as a promising tool to control physicochemical properties of nanoparticles and to accelerate clinical translation. Indeed, microfluidic-based techniques offer more advantages in nanomedicine over batch processes, allowing fine-tuning of process parameters. In particular, the use of microfluidics to produce nanoparticles has paved the way for the development of nano-scaled structures for improved detection and treatment of several diseases. Here, ionotropic gelation is implemented in a custom-designed microfluidic chip to produce different nanoarchitectures based on chitosan-hyaluronic acid polymers. The selected biomaterials provide biocompatibility, biodegradability and non-toxic properties to the formulation, making it promising for nanomedicine applications. Furthermore, results show that morphological structures can be tuned through microfluidics by controlling the flow rates. Aside from the nanostructures, the ability to encapsulate gadolinium contrast agent for magnetic resonance imaging and a dye for optical imaging is demonstrated. In conclusion, the polymer nanoparticles here designed revealed the dual capability of enhancing the relaxometric properties of gadolinium by attaining Hydrodenticity and serving as a promising nanocarrier for multimodal imaging applications.

New application of multimodal ultrasound imaging for identification of myofascial trigger points in the trapezius muscle.

The study aimed to quantify the characteristics of trapezius myofascial trigger points (MTrPs) using shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) and explore the application value of the new ultrasound techniques in identifying MTrPs. Forty patients participated in this study. MTrPs in the trapezius muscle were determined by palpation, and SWE and CEUS were used to quantify the focal and adjacent areas. The elastic modulus values and CEUS parameters between the focal area of MTrPs and adjacent areas were evaluated and compared. Pathological biopsy was performed according to the above two methods, and the pathological tissues were observed by Masson staining, immunohistochemistry and electron microscope. The elastic modulus values were significantly higher for the focal area of MTrPs compared to those for adjacent areas (P<0.05). There were statistically significant differences in MTrP parameters, including peak intensity, mean transit time, and area between the focal and adjacent areas (P<0.05). Masson staining showed that there were inflammatory cell infiltration dominated by lymphocytes in the vascular wall. Electron microscopy showed a large number of fibroblast proliferation, lamellar collagen proliferation and lysosomal deposition; immunohistochemical results: the expression of CD3+, CD4+, CD8+, CD68+, mhc-1+, dys+, CD8 was more than that of CD20 (F=4.385, P=0.036). Combined use of SWE and CEUS provides a new detection approach for quantitative identification of MTrPs in the trapezius muscle, which has high application value and is a method worthy of wider use in clinical practice.

Hybrid nano‐ and microgels doped with photoacoustic contrast agents for cancer theranostics

AbstractPhotoacoustic imaging (PAI) is an emerging noninvasive and inexpensive bioimaging modality, which has stimulated a wide interest in recent years for cancer theranostics. Hybrid nano‐ and microgels have been designed as protective carriers to incorporate PAI contrast agents due to their biocompatibility and biodegradability, high loading capacity, versatile surface chemistry, and stimuli‐responsive properties. These key features offer unprecedented opportunities for the design of innovative multifunctional cancer theranostic agents. This review focuses on the recent development of photoacoustic active nano‐ and microgels for biomedical applications in cancer theranostics and cancer hallmark imaging. The various chemical natures of gels and PAI contrast agents and the elaboration methods of hybrid matrices are summarized and discussed. Their applications in multimodal cancer theranostics and cancer hallmark imaging are presented, highlighting their merits and potential in treatment and diagnosis.

Femtosecond laser generation of bimetallic oxide nanoparticles with potential X-ray absorbing and magnetic functionalities for medical imaging applications

Bimetallic nanoparticles have gained vivid attention due to their unique and synergistic properties. They can be used in fields such as solar cells, optics, sensing, as well as medicine. The generation of bimetallic nanoparticles, containing oxide phases of both magnetic and X-ray attenuating metals for bioimaging applications has been challenging with traditional chemical synthesis methods. An alternative is the generation of nanoparticles from binary oxide ceramics by laser ablation in liquid. However, the applicability of this technique for production of hybrid nanoparticles consisting of magnetic and X-ray absorbing elements has not been demonstrated yet.In this work, novel ceramics composed of bimetallic oxide phases of iron-tantalum, iron-tungsten, and iron-bismuth were produced by a reaction-sintering method. The bulk samples were characterized with scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffractometry. Nanoparticles were produced in aqueous and ethanol solutions by employing a femtosecond laser and characterized with transmission electron microscopy, selected area electron diffraction, and energy dispersive X-ray spectroscopy. The results demonstrated that the production of binary oxide bulk ceramics and their subsequent laser ablation in liquids leads to the successful generation of bimetallic oxide nanoparticles, without a core-shell morphology. In addition, it was found that the ablation threshold fluence of bulk samples as well as the crystallinity of the synthesized nanoparticles is governed by both the nature of the metallic oxide ceramics and the employed liquid. The results pave the way for a single step generation of well-defined bimetallic nanoparticles by laser ablation that could potentially exhibit X-ray and magnetic absorption properties suitable for multimodal imaging applications.

Musiré: multimodal simulation and reconstruction framework for the radiological imaging sciences.

A software-based workflow is proposed for managing the execution of simulation and image reconstruction for SPECT, PET, CBCT, MRI, BLI and FMI packages in single and multimodal biomedical imaging applications. The workflow is composed of a Bash script, the purpose of which is to provide an interface to the user, and to organize data flow between dedicated programs for simulation and reconstruction. The currently incorporated simulation programs comprise GATE for Monte Carlo simulation of SPECT, PET and CBCT, SpinScenario for simulating MRI, and Lipros for Monte Carlo simulation of BLI and FMI. Currently incorporated image reconstruction programs include CASToR for SPECT and PET as well as RTK for CBCT. MetaImage (mhd) standard is used for voxelized phantom and image data format. Meshlab project (mlp) containers incorporating polygon meshes and point clouds defined by the Stanford triangle format (ply) are employed to represent anatomical structures for optical simulation, and to represent tumour cell inserts. A number of auxiliary programs have been developed for data transformation and adaptive parameter assignment. The software workflow uses fully automatic distribution to, and consolidation from, any number of Linux workstations and CPU cores. Example data are presented for clinical SPECT, PET and MRI systems using the Mida head phantom and for preclinical X-ray, PET and BLI systems employing the Digimouse phantom. The presented method unifies and simplifies multimodal simulation setup and image reconstruction management and might be of value for synergistic image research. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.