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Simultaneous positron emission tomography (PET)/magnetic resonance imaging provides concurrent information about anatomic, functional, and molecular changes in disease. We are developing a second generation MR-compatible RF-penetrable TOF-PET insert. The insert has a smaller scintillation crystal size and ring diameter compared to clinical whole-body PET scanners, resulting in higher spatial resolution and sensitivity. This paper reports the initial system performance of this full-ring PET insert. The global photopeak energy resolution and global coincidence time resolution, 11.74 ± 0.03 % FWHM and 238.1 ± 0.5 ps FWHM, respectively, are preserved as we scaled up the system to a full ring comprising 12, 288 LYSO-SiPM channels (crystal size: 3.2 × 3.2 × 20 mm 3 ). Throughout a ten-hour experiment, the system performance remained stable, exhibiting a less than 1% change in all measured parameters. In a resolution phantom study, the system successfully resolved all 2.8 mm diameter rods, achieving an average VPR of 0.28 ± 0.08 without TOF and 0.24 ± 0.07 with TOF applied. Moreover, the implementation of TOF in the Hoffman phantom study also enhanced image quality. Initial MR compatibility studies of the full PET ring were performed with it unpowered as a milestone to focus on looking for material and geometry-related artifacts. During all MR studies, the MR body coil functioned as both the transmit and receive coil, and no observable artifacts were detected. As expected, using the body coil also as the RF receiver, MR image signal-to-noise ratio exhibited degradation (∼30%), so we are developing a high quality receive-only coil that resides inside the PET ring., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Significance: Esophageal cancer is becoming increasingly prevalent in Western countries. Early detection is crucial for effective treatment. Multimodal imaging combining optical coherence tomography (OCT) with complementary optical imaging techniques may provide enhanced diagnostic capabilities by simultaneously assessing tissue morphology and biochemical content., Aim: We aim to develop a tethered capsule endoscope (TCE) that can accommodate a variety of point-scanning techniques in addition to OCT without requiring design iterations on the optical or mechanical design., Approach: We propose a TCE utilizing exclusively reflective optics to focus and steer light from and to a double-clad fiber. Specifically, we use an ellipsoidal mirror to achieve finite conjugation between the fiber tip and the imaging plane., Results: We demonstrate a functional all-reflective TCE. We first detail the design, fabrication, and assembly steps required to obtain such a device. We then characterize its performance and demonstrate combined OCT at 1300 nm and visible spectroscopic imaging in the 500- to 700-nm range. Finally, we discuss the advantages and limitations of the proposed design., Conclusions: An all-reflective TCE is feasible and allows for achromatic high-quality imaging. Such a device could be utilized as a platform for testing various combinations of modalities to identify the optimal candidates without requiring design iterations., (© 2024 The Authors.)

As artificial intelligence technology gains widespread adoption in biomedicine, the exploration of integrating biofluidic Raman spectroscopy for enhanced disease diagnosis opens up new prospects for the practical application of Raman spectroscopy in clinical settings. However, for systemic lupus erythematosus (SLE), origin Raman spectral data (ORS) have relatively weak signals, making it challenging to obtain ideal classification results. Although the surface enhancement technique can enhance the scattering signal of Raman spectroscopic data, the sensitivity of the SERS substrate to airborne impurities and the inhomogeneous distribution of hotspots degrade part of the signal. To fully utilize both kinds of data, this paper proposes a two-branch residual-attention network (DBRAN) fusion technique, which allows the ORS to complement the degraded portion and thus improve the model's classification accuracy. The features are extracted using the residual module, which retains the original features while extracting the deep features. At the same time, the study incorporates the attention module in both the upper and lower branches to handle the weight allocation of the two modal features more efficiently. The experimental results demonstrate that both the low-level fusion method and the intermediate-level fusion method can significantly improve the diagnostic accuracy of SLE disease classification compared with a single modality, in which the intermediate-level fusion of DBRAN achieves 100% classification accuracy, sensitivity, and specificity. The accuracy is improved by 10% and 7% compared with the ORS unimodal and the SERS unimodal modalities, respectively. The experiment, by fusing the multimodal spectral, realized rapid diagnosis of SLE disease by fusing multimodal spectral data, which provides a reference idea in the field of Raman spectroscopy and can be further promoted to clinical practical applications in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Magnetic resonance imaging (MRI) is a common technique in image-guided neurosurgery (IGN). Recent research explores the integration of methods like ultrasound and tomography, among others, with hyperspectral (HS) imaging gaining attention due to its non-invasive real-time tissue classification capabilities. The main challenge is the registration process, often requiring manual intervention. This work introduces an automatic, markerless method for aligning HS images with MRI., Methods: This work presents a multimodal system that combines RGB-Depth (RGBD) and HS cameras. The RGBD camera captures the patient's facial geometry, which is used for registration with the preoperative MR through ICP. Once MR-depth registration is complete, the integration of HS data is achieved using a calibrated homography transformation. The incorporation of external tracking with a novel calibration method allows camera mobility from the registration position to the craniotomy area. This methodology streamlines the fusion of RGBD, HS and MR images within the craniotomy area., Results: Using the described system and an anthropomorphic phantom head, the system has been characterised by registering the patient's face in 25 positions and 5 positions resulted in a fiducial registration error of 1.88 ± 0.19 mm and a target registration error of 4.07 ± 1.28 mm, respectively., Conclusions: This work proposes a new methodology to automatically register MR and HS information with a sufficient accuracy. It can support the neurosurgeons to guide the diagnosis using multimodal data over an augmented reality representation. However, in its preliminary prototype stage, this system exhibits significant promise, driven by its cost-effectiveness and user-friendly design., (© 2024. The Author(s).)

Background: High-precision neurosurgical targeting in nonhuman primates (NHPs) often requires presurgical anatomical mapping with noninvasive neuroimaging techniques (MRI, CT, PET), allowing for translation of individual anatomical coordinates to surgical stereotaxic apparatus. Given the varied tissue contrasts that these imaging techniques produce, precise alignment of imaging-based coordinates to surgical apparatus can be cumbersome. MRI-compatible stereotaxis with radiopaque fiducial markers offer a straight-forward and reliable solution, but existing commercial options do not fit in conformal head coils that maximize imaging quality., New Method: We developed a compact MRI-compatible stereotaxis suitable for a variety of NHP species (Macaca mulatta, Macaca fascicularis, and Cebus apella) that allows multimodal alignment through technique-specific fiducial markers., Comparison With Existing Methods: With the express purpose of compatibility with clinically available MRI, CT, and PET systems, the frame is no larger than a human head, while allowing for imaging NHPs in the supinated position. This design requires no marker implantation, special software, or additional knowledge other than the operation of a common large animal stereotaxis., Results: We demonstrated the applicability of this 3D-printable apparatus across a diverse set of experiments requiring presurgical planning: 1) We demonstrate the accuracy of the fiducial system through a within-MRI cannula insertion and subcortical injection of a viral vector. 2) We also demonstrated accuracy of multimodal (MRI and CT) alignment and coordinate transfer to guide a surgical robot electrode implantation for deep-brain electrophysiology., Conclusions: The computer-aided design files and engineering drawings are publicly available, with the modular design allowing for low cost and manageable manufacturing., Competing Interests: Declaration of Competing Interest none, (Copyright © 2024. Published by Elsevier B.V.)

Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy are powerful analytical techniques widely used separately in different fields of study. Integrating these two powerful spectroscopic techniques into one device represents a groundbreaking advance in multimodal imaging. This new combination which merges the molecular vibrational information from Raman spectroscopy with the ability of FTIR to study polar bonds, creates a unique and complete analytical tool. Through a detailed examination of the microscope's operation and case studies, this article illustrates how this integrated analytical instrument can provide more thorough and accurate analysis than traditional methods, potentially revolutionising analytical sample characterisation. This article aims to present the features and possible uses of a unified instrument merging FTIR and Raman spectroscopy for multimodal imaging. It particularly focuses on the technological progress and collaborative benefits of these two spectroscopic techniques within the microscope system. By emphasising this approach's unique benefits and improved analytical capabilities, the authors aim to illustrate its applicability in diverse scientific and industrial sectors.

Depression is a major psychological disorder with a growing impact worldwide. Traditional methods for detecting the risk of depression, predominantly reliant on psychiatric evaluations and self-assessment questionnaires, are often criticized for their inefficiency and lack of objectivity. Advancements in deep learning have paved the way for innovations in depression risk detection methods that fuse multimodal data. This paper introduces a novel framework, the Audio, Video, and Text Fusion-Three Branch Network (AVTF-TBN), designed to amalgamate auditory, visual, and textual cues for a comprehensive analysis of depression risk. Our approach encompasses three dedicated branches-Audio Branch, Video Branch, and Text Branch-each responsible for extracting salient features from the corresponding modality. These features are subsequently fused through a multimodal fusion (MMF) module, yielding a robust feature vector that feeds into a predictive modeling layer. To further our research, we devised an emotion elicitation paradigm based on two distinct tasks-reading and interviewing-implemented to gather a rich, sensor-based depression risk detection dataset. The sensory equipment, such as cameras, captures subtle facial expressions and vocal characteristics essential for our analysis. The research thoroughly investigates the data generated by varying emotional stimuli and evaluates the contribution of different tasks to emotion evocation. During the experiment, the AVTF-TBN model has the best performance when the data from the two tasks are simultaneously used for detection, where the F1 Score is 0.78, Precision is 0.76, and Recall is 0.81. Our experimental results confirm the validity of the paradigm and demonstrate the efficacy of the AVTF-TBN model in detecting depression risk, showcasing the crucial role of sensor-based data in mental health detection., Competing Interests: The authors declare no conflicts of interest.

Background: In recent years, PD-L1 has been primarily utilized as an immune checkpoint marker in cancer immunotherapy. However, due to tumor heterogeneity, the response rate to such therapies often falls short of expectations. In addition to its role in immunotherapy, PD-L1 serves as a specific target on the surface of tumor cells for targeted diagnostic and therapeutic interventions. There is an absence of a fully developed PD-L1-targeted diagnostic and therapeutic probe for clinical use, which constrains the exploration and clinical exploitation of this target., Methods and Results: In this study, we engineered a PD-L1-targeted probe with multimodal imaging and dual therapeutic functionalities utilizing organic melanin nanoparticles. Functionalization with the WL12-SH peptide endowed the nanoprobe with specific targeting capabilities. Subsequent radiolabeling with 89 Zr (half-life: 100.8 hours) and chelation of Mn 2+ ions afforded the probe the capacity for simultaneous PET and MRI imaging modalities. Cellular uptake assays revealed pronounced specificity, with -positive cells exhibiting significantly higher uptake than -negative counterparts (p < 0.05). Dual-modal PET/MRI imaging delineated rapid and sustained accumulation at the neoplastic site, yielding tumor-to-non-tumor (T/NT) signal ratios at 24 hours post-injection of 16.67±3.45 for PET and 6.63±0.64 for MRI, respectively. We conjugated the therapeutic radionuclide 131 I (half-life: 8.02 days) to the construct and combined low-dose radiotherapy and photothermal treatment (PTT), culminating in superior antitumor efficacy while preserving a high safety profile. The tumors in the cohort receiving the dual-modality therapy exhibited significantly reduced volume and weight compared to those in the control and monotherapy groups., Conclusion: We developed and applied a novel -targeted multimodal theranostic nanoprobe, characterized by its high specificity and superior imaging capabilities as demonstrated in PET/MRI modalities. Furthermore, this nanoprobe facilitates potent therapeutic efficacy at lower radionuclide doses when used in conjunction with PTT., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 He et al.)

An implantable loop recorder (ILR) is a leadless rectangular device used for prolonged electrocardiographic monitoring for up to 3 years. This miniaturized device, inserted subcutaneously, allows clinicians to investigate possible cardiac rhythm disturbances in patients suffering from recurrent unexplained syncope. As the age of the population increases rapidly and the number of ILR patients amplifies, the clinical significance of ILRs is undeniable. Although radioopaque and easily seen on plain chest radiographs and other imaging modalities, ILRs may represent a challenge for clinicians and radiologists to recognize their classic appearance and differentiate them from numerous other cardiac devices. This article aims to summarize current literature on ILRs, their basic function, types, and indications for implantation, but most of all, it aims to familiarize clinicians and radiologists with common imaging features of these devices, safety issues, and artifact-reducing methods. Specifically, this review discusses the typical appearance of ILRs on major diagnostic imaging modalities, including chest X-ray, mammography, ultrasonography, computed tomography, and magnetic resonance imaging (MRI). Furthermore, optimization strategies to mitigate image artifacts and safety issues regarding MRI are discussed., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

High positive margin rates in oncologic breast-conserving surgery are a pressing clinical problem. Volumetric X-ray scanning is emerging as a powerful ex vivo specimen imaging technique for analyzing resection margins, but X-rays lack contrast between non-malignant and malignant fibrous tissues. In this study, combined micro-CT and wide-field optical image radiomics were developed to classify malignancy of breast cancer tissues, demonstrating that X-ray/optical radiomics improve malignancy classification. Ninety-two standardized features were extracted from co-registered micro-CT and optical spatial frequency domain imaging samples extracted from 54 breast tumors exhibiting seven tissue subtypes confirmed by microscopic histological analysis. Multimodal feature sets improved classification performance versus micro-CT alone when adipose samples were included (AUC = 0.88 vs. 0.90; p-value = 3.65e-11) and excluded, focusing the classification task on exclusively non-malignant fibrous versus malignant tissues (AUC = 0.78 vs. 0.85; p-value = 9.33e-14). Extending the radiomics approach to high-dimensional optical data-termed "optomics" in this study-offers a promising optical image analysis technique for cancer detection. Radiomic feature data and classification source code are publicly available., (© 2021. The Author(s).)

Purpose: The FUSION-X-US-II prototype was developed to combine 3D-automated breast ultrasound (ABUS) and digital breast tomosynthesis in a single device without decompressing the breast. We evaluated the technical function, feasibility of the examination workflow, image quality, breast tissue coverage and patient comfort of the ABUS device of the new prototype., Methods: In this prospective feasibility study, the FUSION-X-US-II prototype was used to perform ABUS in 30 healthy volunteers without history of breast cancer. The ABUS images of the prototype were interpreted by a physician with specialization in breast diagnostics. Any detected lesions were measured and classified using BI-RADS ® scores. Image quality was rated subjectively by the physician and coverage of the breast was measured. Patient comfort was evaluated by a questionnaire after the examination., Results: One hundred and six scans were performed (61 × CC, 23 × ML, 22 × MLO) in 60 breasts. Image acquisition and processing by the prototype was fast and accurate. Breast coverage by ABUS was approximately 90.8%. Sixteen breast lesions (all benign, classified as BIRADS ® 2) were identified. The examination was tolerated by all patients., Conclusion: The FUSION-X-US-II prototype allows a rapid ABUS scan with mostly high patient comfort. Technical developments resulted in an improvement of quality and coverage compared to previous prototype versions. The results are encouraging for a test of the prototype in a clinical setting in combination with tomosynthesis., (© 2021. The Author(s).)

Background: Gastric inflammation is a major risk factor for gastric cancer. Current endoscopic methods are not able to efficiently detect and characterize gastric inflammation, leading to a sub-optimal patients' care. New non-invasive methods are needed. Reflectance mucosal light analysis is of particular interest in this context. The aim of our study was to analyze reflectance light and specific autofluorescence signals, both in humans and in a mouse model of gastritis., Methods: We recruited patients undergoing gastroendoscopic procedure during which reflectance was analysed with a multispectral camera. In parallel, the gastritis mouse model of Helicobacter pylori infection was used to investigate reflectance from ex vivo gastric samples using a spectrometer. In both cases, autofluorescence signals were measured using a confocal microscope., Findings: In gastritis patients, reflectance modifications were significant in near-infrared spectrum, with a decrease between 610 and 725 nm and an increase between 750 and 840 nm. Autofluorescence was also modified, showing variations around 550 nm of emission. In H. pylori infected mice developing gastric inflammatory lesions, we observed significant reflectance modifications 18 months after infection, with increased intensity between 617 and 672 nm. Autofluorescence was significantly modified after 1, 3 and 6 months around 550 and 630 nm. Both in human and in mouse, these reflectance data can be considered as biomarkers and accurately predicted inflammatory state., Interpretation: In this pilot study, using a practical measuring device, we identified in humans, modification of reflectance spectra in the visible spectrum and for the first time in near-infrared, associated with inflammatory gastric states. Furthermore, both in the mouse model and humans, we also observed modifications of autofluorescence associated with gastric inflammation. These innovative data pave the way to deeper validation studies on larger cohorts, for further development of an optical biopsy system to detect gastritis and finally to better surveil this important gastric cancer risk factor., Funding: The project was funded by the ANR EMMIE (ANR-15-CE17-0015) and the French Gastroenterology Society (SNFGE)., Competing Interests: Declaration of Competing Interest Authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Many cognitive processes require communication between the neocortex and the hippocampus. However, coordination between large-scale cortical dynamics and hippocampal activity is not well understood, partially due to the difficulty in simultaneously recording from those regions. In the present study, we developed a flexible, insertable and transparent microelectrode array (Neuro-FITM) that enables investigation of cortical-hippocampal coordinations during hippocampal sharp-wave ripples (SWRs). Flexibility and transparency of Neuro-FITM allow simultaneous recordings of local field potentials and neural spiking from the hippocampus during wide-field calcium imaging. These experiments revealed that diverse cortical activity patterns accompanied SWRs and, in most cases, cortical activation preceded hippocampal SWRs. We demonstrated that, during SWRs, different hippocampal neural population activity was associated with distinct cortical activity patterns. These results suggest that hippocampus and large-scale cortical activity interact in a selective and diverse manner during SWRs underlying various cognitive functions. Our technology can be broadly applied to comprehensive investigations of interactions between the cortex and other subcortical structures.

Multimodal imaging-the ability to acquire images of an object through more than one imaging mode simultaneously-has opened additional perspectives in areas ranging from astronomy to medicine. In this paper, we report progress toward combining optical and magnetic resonance (MR) imaging in such a "dual" imaging mode. They are attractive in combination because they offer complementary advantages of resolution and speed, especially in the context of imaging in scattering environments. Our approach relies on a specific material platform, microdiamond particles hosting nitrogen vacancy (NV) defect centers that fluoresce brightly under optical excitation and simultaneously "hyperpolarize" lattice [Formula: see text] nuclei, making them bright under MR imaging. We highlight advantages of dual-mode optical and MR imaging in allowing background-free particle imaging and describe regimes in which either mode can enhance the other. Leveraging the fact that the two imaging modes proceed in Fourier-reciprocal domains (real and k-space), we propose a sampling protocol that accelerates image reconstruction in sparse-imaging scenarios. Our work suggests interesting possibilities for the simultaneous optical and low-field MR imaging of targeted diamond nanoparticles., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

In this study, we aimed to compare clinical and technical outcomes between pediatric patients who underwent percutaneous nephrolithotomy (PCNL) under fluoroscopy (FL) and those that underwent this procedure under FL with ultrasound assistance (FLUSA). The data of 66 PCNL patients were analyzed retrospectively. Renal puncture was successful in 22 patients in the FLUSA group and 44 patients in the FL group. In all cases, FL was used for tract dilation and confirmation of ureteral catheter positioning at the beginning of the procedure. The sample consisted of 46 males and 20 females with a mean age of 7.2 ± 2.1 years (range 1-17 years). Stone size varied from 8.0 to 75.4 mm, and 89% of patients achieved a completely stone-free state. The median puncture time was 130.5 ± 25.3 s for FLUSA and 295 ± 82.8 s for FL, the median fluoroscopic screening time was 95 ± 33 and 230 ± 116 s, respectively, and the median radiation dose was 19.04 ± 9.9 dGy/cm 2 and 54 ± 21.4 dGy/cm 2 , respectively. The median puncture time, fluoroscopic screening time, and radiation dose were statistically lower in the FLUSA group (p = 0.001, Mann-Whitney U test). The greatest problem in PCNL is the use of fluoroscopy. Due to some anatomical differences from adults, applying PCNL in pediatric patients using only ultrasound may decrease the success rate. Puncture with ultrasound significantly reduces the radiation dose in children. Puncture with ultrasound and dilation under fluoroscopy is a successful and safe treatment method with low morbidity and high success rates and shorter hospital stay in pediatric patients.

Objective: Safe surgery requires the accurate discrimination of tissue intraoperatively. We assess the feasibility of using multispectral imaging and deep learning to enhance surgical vision by automated identification of normal human head and neck tissues., Study Design: Construction and feasibility testing of novel multispectral imaging system for surgery., Setting: Academic university hospital., Subjects and Methods: Multispectral images of fresh-preserved human cadaveric tissues were captured with our adapted digital operating microscope. Eleven tissue types were sampled, each sequentially exposed to 6 lighting conditions. Two convolutional neural network machine learning models were developed to classify tissues based on multispectral and white-light color images (ARRInet-M and ARRInet-W, respectively). Blinded otolaryngology residents were asked to identify tissue specimens from white-light color images, and their performance was compared with that of the ARRInet models., Results: A novel multispectral imaging system was developed with minimal adaptation to an existing digital operating microscope. With 81.8% accuracy in tissue identification of full-size images, the multispectral ARRInet-M classifier outperformed the white-light-only ARRInet-W model (45.5%) and surgical residents (69.7%). Challenges with discrimination occurred with parotid vs fat and blood vessels vs nerve., Conclusions: A deep learning model using multispectral imaging outperformed a similar model and surgical residents using traditional white-light imaging at the task of classifying normal human head and neck tissue ex vivo. These results suggest that multispectral imaging can enhance surgical vision and augment surgeons' ability to identify tissues during a procedure.

Image-guided and robotic surgery based on endoscopic imaging technologies can enhance cancer treatment by ideally removing all cancerous tissue and avoiding iatrogenic damage to healthy tissue. Surgeons evaluate the tumor margins at the cost of impeding surgical workflow or working with dimmed surgical illumination, since current endoscopic imaging systems cannot simultaneous and real-time color and near-infrared (NIR) fluorescence imaging under normal surgical illumination. To overcome this problem, a bio-inspired multimodal 3D endoscope combining the excellent characteristics of human eyes and compound eyes of mantis shrimp is proposed. This 3D endoscope, which achieves simultaneous and real-time imaging of three-dimensional stereoscopic, color, and NIR fluorescence, consists of three parts: a broad-band binocular optical system like as human eye, an optical relay system, and a multiband sensor inspired by the mantis shrimp's compound eye. By introducing an optical relay system, the two sub-images after the broad-band binocular optical system can be projected onto one and the same multiband sensor. A series of experiments demonstrate that this bio-inspired multimodal 3D endoscope not only provides surgeons with real-time feedback on the location of tumor tissue and lymph nodes but also creates an immersive experience for surgeons without impeding surgical workflow. Its excellent characteristics and good scalability can promote the further development and application of image-guided and robotic surgery.

Radiographic imaging with x-rays and protons is an omnipresent tool in basic research and applications in industry, material science and medical diagnostics. The information contained in both modalities can often be valuable in principle, but difficult to access simultaneously. Laser-driven solid-density plasma-sources deliver both kinds of radiation, but mostly single modalities have been explored for applications. Their potential for bi-modal radiographic imaging has never been fully realized, due to problems in generating appropriate sources and separating image modalities. Here, we report on the generation of proton and x-ray micro-sources in laser-plasma interactions of the focused Texas Petawatt laser with solid-density, micrometer-sized tungsten needles. We apply them for bi-modal radiographic imaging of biological and technological objects in a single laser shot. Thereby, advantages of laser-driven sources could be enriched beyond their small footprint by embracing their additional unique properties, including the spectral bandwidth, small source size and multi-mode emission.

Imaging mass spectrometry has become a mature molecular mapping technology that is used for molecular discovery in many medical and biological systems. While powerful by itself, imaging mass spectrometry can be complemented by the addition of other orthogonal, chemically informative imaging technologies to maximize the information gained from a single experiment and enable deeper understanding of biological processes. Within this review, we describe MALDI, SIMS, and DESI imaging mass spectrometric technologies and how these have been integrated with other analytical modalities such as microscopy, transcriptomics, spectroscopy, and electrochemistry in a field termed multimodal imaging. We explore the future of this field and discuss forthcoming developments that will bring new insights to help unravel the molecular complexities of biological systems, from single cells to functional tissue structures and organs.

Purpose: Small animal irradiation is crucial to the investigation of radiobiological mechanisms. The paradigm of clinical radiation therapy is trending toward high-precision, stereotactic treatment. However, translating this scheme to small animal irradiation is challenging owing to the lack of high-quality image guidance. To overcome this obstacle, we developed a multimodality image guided precision radiation platform., Methods and Materials: The platform consists of 4 modules: x-ray computed tomography (CT), bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and radiation therapy. CT provides animal anatomy and material density for radiation dose calculation, as well as body contour for BLT and FMT reconstruction. BLT and FMT provide tumor localization to guide radiation beams and molecular activity to evaluate treatment outcome. Furthermore, we developed a Monte Carlo-based treatment planning system (TPS) for 3-dimensional dose calculation, calibrated it using radiochromic films sandwiched in a water-equivalent phantom, and validated it using in vivo dosimeters surgically implanted into euthanized mice (n = 4). Finally, we performed image guided irradiation on mice bearing orthotopic breast and prostate tumors and confirmed radiation delivery using γH2AX histology., Results: The Monte Carlo-based TPS was successfully calibrated by benchmarking simulation dose against film measurement. For in vivo dosimetry measured in the euthanized mice, the average difference between the TPS calculated dose and measured dose was 3.86% ± 1.12%. Following the TPS-generated treatment plan, we successfully delivered 20 Gy dose to an animal bearing an orthotopic prostate tumor using 4 BLT-guided radiation beams and 5 Gy dose to an animal bearing an orthotopic breast tumor using a single FMT-guided radiation beam. γH2AX histology presented significantly more DNA damage in irradiated tumors and thus validated the dose delivery accuracy., Conclusions: Combined with Monte Carlo TPS, this multimodality CT/BLT/FMT image guided small animal radiation platform can specifically localize tumors, accurately calculate dose distribution, precisely guide radiation delivery, and molecularly evaluate treatment response. It provides an advanced toolset for radiobiology and translational cancer research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Photoacoustic microscopy is a novel, non-ionizing, non-invasive imaging technology that evaluates tissue absorption of short-pulsed light through the sound waves emitted by the tissue and has numerous biomedical applications. In this study, a custom-built multimodal imaging system, including photoacoustic microscopy (PAM) and optical coherence tomography (OCT), has been developed to evaluate choroidal vascular occlusion (CVO). CVO was performed on three living rabbits using laser photocoagulation. Longitudinal imaging of CVO was obtained using multiple imaging tools such as color fundus photography, fluorescein angiography, indocyanine green angiography (ICGA), OCT, and PAM. PAM images were acquired at different wavelengths, ranging from 532 to 700 nm. The results demonstrate that the CVO was clearly observed on PAM in both two dimensions (2D) and 3D with high resolution longitudinally over 28 days. In addition, the location and margin of the CVO were distinguished from the surrounding choroidal vasculature after the injection of ICG contrast agent. PAM imaging was achieved using a laser energy of approximately 80 nJ, which is about half of the American National Standards Institute safety limit. The proposed imaging technique may provide a potential tool for the evaluation of different chorioretinal vascular disease pathogeneses and other biological studies.

We develop a multimodal imaging platform, combining depth-resolved scattering contrast from spectral-domain optical coherence tomography (SD-OCT) with complementary, non-contact absorption contrast using photoacoustic remote sensing (PARS) microscopy. The system provides a widefield OCT mode using a telecentric scan lens, and a high-resolution, dual-contrast mode using a 0.26 numerical aperture apochromatic objective. An interlaced acquisition approach is used to achieve simultaneous, co-registered imaging. The SD-OCT modality provides a 9.7 µm axial resolution. Comprehensive in vivo imaging of a nude mouse ear is demonstrated, with the SD-OCT scattering intensity revealing dermal morphology, and PARS microscopy providing a map of microvasculature.

To investigate the diagnostic value of multimodal ultrasound imaging composed of conventional ultrasonography (US), contrast-enhanced ultrasonography (CEUS), and shear wave elastography (SWE) for liver tumors.Between October 2017 and October 2019, US, CEUS, and SWE examinations of a total of 158 liver tumors in 136 patients at The First Affiliated Hospital of Nanchang University were performed. The histopathological or imaging diagnostic results were used as controls to evaluate the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of US, CEUS, SWE, and multimodal ultrasound imaging, which combines these 3 modes, in the differential diagnosis of benign and malignant liver tumors.Among the 158 tumors, there were 64 benign tumors, including 55 cases of hepatic hemangioma, 3 cases of focal nodular hyperplasia of the liver, 4 cases of hepatic cyst, and 2 cases of focal nonuniform distribution of fat in the liver. There were 94 malignant tumors, including 32 cases of hepatocellular carcinoma, 22 cases of intrahepatic cholangiocellular carcinoma, 29 cases of metastatic liver cancer, and 11 cases of dysplastic nodules in cirrhotic liver. In the diagnosis of benign and malignant liver tumors, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 82.56%, 68.06%, 75.96%, 75.53%, and 76.56% for US; 92.39%, 86.36%, 89.87%, 90.43%, and 89.06% for CEUS; 87.14%, 76.81%, 82.91%, 82.98%, and 82.81% for SWE; and 97.85%, 95.38%, 96.83%, 96.81%, and 96.88% for multimodal ultrasound imaging, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were all significantly higher for multimodal ultrasound imaging than those values for US, CEUS, and SWE (all P < .05). The areas under the receiver operating characteristic curve for US, CEUS, SWE, and multimodal ultrasound imaging in the diagnosis of benign and malignant liver tumors were 0.760, 0.897, 0.829, and 0.968, respectively.US, CEUS, and SWE all have diagnostic value in the diagnosis of benign and malignant liver tumors. Multimodal ultrasound imaging could significantly increase the accuracy of the diagnosis of benign and malignant liver tumors and has higher value for clinical application.

Computed tomography (CT) in the treatment position is currently indispensable for planning radiation therapy. Other imaging modalities, such as magnetic resonance imaging (MRI) and positron emission-tomography (PET), can be used to improve the definition of the tumour and/or healthy tissue but also to provide functional data of the target volume. Accurate image registration is essential for treatment planning, so MRI and PET scans should be registered at the planning CT scan. Hybrid PET/MRI scans with a hard plane can be used but pose the problem of the absence of CT scans. Finally, techniques for moving the patient on a rigid air-cushioned table allow PET/CT/MRI scans to be performed in the treatment position while limiting the patient's movements exist. At the same time, the advent of MRI-linear accelerator systems allows to redefine image-guided radiotherapy and to propose treatments with daily recalculation of the dose. The place of PET during treatment remains more confidential and currently only in research and prototype status. The same development of imaging during radiotherapy is underway in proton therapy., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objective: To introduce the application of robot-assisted frameless stereoelectroencephalography (SEEG) based on multimodal image fusion technology in pediatric refractory epilepsy in a pediatric center from a developing country., Methods: We retrospectively evaluated pediatric patients with drug-resistant epilepsy who underwent SEEG monitoring at the Children's Hospital of Fudan University from July 2014 to August 2017. Application of multimodal image fusion technology in SEEG was described in detail. Seizure outcomes were assessed according to the International League Against Epilepsy classification., Results: A total of 208 patients were initially eligible and underwent a rigorous phase I evaluation. SEEG explorations were performed in 20 patients who entered phase II assessment (11 male and 9 female patients) with a median age of 7.99 ± 4.07 years. In total, 181 electrodes were implanted (9 per implantation), among which 16 implantations were unilateral (6 left and 10 right) and 4 were bilateral. The mean operating time was 3 hours and no obvious hemorrhage occurred. Electrode displacement and pneumocephalus were observed in 1 and 2 patients, respectively. Thirteen and 7 patients underwent tailored resection and radiofrequency thermocoagulation, respectively. Among resection cases, focal cortical dysplasia was the predominant pathologic type. The overall seizure outcome after a mean follow-up of 2.65 years was International League Against Epilepsy class 1 in 13, class 2 in 2, class 3 in 3, class 4 in 1, and class 5 in 1 patient, respectively., Conclusions: The combination of multimodal image fusion and frameless robot-assisted SEEG is demonstrated to be safe and effective on children with refractory epilepsy in developing countries., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Prostate cancer is one of the most common cancers among men and its early detection is critical for its successful treatment. The use of multimodal imaging, such as MR-PET, is most advantageous as it is able to provide detailed information about the prostate. However, as the human prostate is flexible and can move into different positions under external conditions, it is important to localise the focused region-of-interest using both MRI and PET under identical circumstances. In this work, we designed five commonly used linear and quadrature radiofrequency surface coils suitable for hybrid MR-PET use in endorectal applications. Due to the endorectal design and the shielded PET insert, the outer face of the coils investigated was curved and the region to be imaged was outside the volume of the coil. The tilting angles of the coils were varied with respect to the main magnetic field direction. This was done to approximate the various positions from which the prostate could be imaged. The transmit efficiencies and safety excitation efficiencies from simulations, together with the signal-to-noise ratios from the MR images were calculated and analysed. Overall, it was found that the overlapped loops driven in quadrature were superior to the other types of coils we tested. In order to determine the effect of the different coil designs on PET, transmission scans were carried out, and it was observed that the differences between attenuation maps with and without the coils were negligible. The findings of this work can provide useful guidance for the integration of such coil designs into MR-PET hybrid systems in the future.

Transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) thermal ablation is under clinical investigation for non-invasive neurosurgery, though its use is restricted to central brain targets due primarily to skull heating effects. The combination of FUS and contrast agent microbubbles greatly reduces the ultrasound exposure levels needed to ablate brain tissue and may help facilitate the use of transcranial FUS ablation throughout the brain. However, sources of variability exist during microbubble-mediated FUS procedures that necessitate the continued development of systems and methods for online treatment monitoring and control, to ensure that excessive and/or off-target bioeffects are not induced from the exposures. Methods: Megahertz-rate three-dimensional (3D) microbubble imaging in vivo was performed during nonthermal ablation in rabbit brain using a clinical-scale prototype transmit/receive hemispherical phased array system. Results: In-vivo volumetric acoustic imaging over microsecond timescales uncovered spatiotemporal microbubble dynamics hidden by conventional whole-burst temporal averaging. Sonication-aggregate ultrafast 3D source field intensity data were predictive of microbubble-mediated tissue damage volume distributions measured post-treatment using MRI and confirmed via histopathology. Temporal under-sampling of acoustic emissions, which is common practice in the field, was found to impede performance and highlighted the importance of capturing adequate data for treatment monitoring and control purposes. Conclusion: The predictive capability of ultrafast 3D microbubble imaging, reported here for the first time, will enable future microbubble-mediated FUS treatments with unparalleled precision and accuracy, and will accelerate the clinical translation of nonthermal tissue ablation procedures both in the brain and throughout the body., Competing Interests: Competing Interests: K.H. and R.M.J. are inventors on issued patents and pending patent applications related to the methods used in this study., (© The author(s).)

Meniere's disease remains enigmatic, and has no treatment with sufficient evidence. The characteristic histopathological finding is endolymphatic hydrops, suggesting either an overproduction or decreased reabsorption of endolymph in the human inner ear. This study presents the first analysis of the vascular plexus around the human endolymphatic duct using micro computed tomography and coherent synchrotron radiation with phase contrast imaging. Using a software program, data were processed by volume-rendering with scalar opacity mapping to create transparent three-dimensional reconstructions. A rich vascular plexus was discovered around the endolymphatic duct that drained into collecting channels, linked to the vestibular venous outflow system. This network is believed to make up the principal route for endolymph outflow, and its associated malfunction may result in endolymphatic hydrops and Meniere's disease.

As the complications of atherosclerosis such as myocardial infarction and stroke are still one of the leading causes of mortality worldwide, the development of new diagnostic tools for the early detection of plaque instability and thrombosis is urgently needed. Advanced molecular imaging probes based on functional nanomaterials in combination with cutting edge imaging techniques are now paving the way for novel and unique approaches to monitor the inflammatory progress in atherosclerosis. This review focuses on the development of various molecular probes for the diagnosis of plaques and thrombosis in atherosclerosis, along with perspectives of their diagnostic applications in cardiovascular diseases. Specifically, we summarize the biological targets that can be used for atherosclerosis and thrombosis imaging. Then we describe the emerging molecular imaging techniques based on the utilization of engineered nanoprobes together with their challenges in clinical translation.

Background: In this study, a novel pelvic phantom was developed and used to assess the visibility and presence of artefacts from different types of commercial fiducial markers (FMs) on multi-modality imaging relevant to prostate cancer., Methods and Materials: The phantom was designed with 3D printed hollow cubes in the centre. These cubes were filled with gel to mimic the prostate gland and two parallel PVC rods were used to mimic bones in the pelvic region. Each cube was filled with gelatine and three unique FMs were positioned with a clinically-relevant spatial distribution. The FMs investigated were; Gold Marker (GM) CIVCO, GM RiverPoint, GM Gold Anchor (GA) line and ball shape, and polymer marker (PM) from CIVCO. The phantom was scanned using several imaging modalities typically used to image prostate cancer patients; MRI, CT, CBCT, planar kV-pair, ExacTrac, 6MV, 2.5MV and integrated EPID imaging. The visibility of the markers and any observed artefacts in the phantom were compared to in-vivo scans of prostate cancer patients with FMs., Results: All GMs were visible in volumetric scans, however, they also had the most visible artefacts on CT and CBCT scans, with the magnitude of artefacts increasing with FM size. PM FMs had the least visible artefacts in volumetric scans but they were not visible on portal images and had poor visibility on lateral kV images. The smallest diameter GMs (GA) were the most difficult GMs to identify on lateral kV images., Conclusion: The choice between different FMs is also dependent on the adopted IGRT strategy. PM was found to be superior to investigated gold markers in the most commonly used modalities in the management of prostate cancer; CT, CBCT and MRI imaging.

Quantitative assessment of functional perfusion capacity and vessel architecture is critical when validating biomaterials for regenerative medicine purposes and requires high-tech analytical methods. Here, combining two clinically relevant imaging techniques, (magnetic resonance imaging; MRI and microcomputed tomography; MicroCT) and using the chorioallantoic membrane (CAM) assay, we present and validate a novel functional and morphological three-dimensional (3D) analysis strategy to study neovascularization in biomaterials relevant for bone regeneration. Using our new pump-assisted approach, the two scaffolds, Optimaix (laminar structure mimicking entities of the diaphysis) and DegraPol (highly porous resembling spongy bone), were shown to directly affect the architecture of the ingrowing neovasculature. Perfusion capacity (MRI) and total vessel volume (MicroCT) strongly correlated for both biomaterials, suggesting that our approach allows for a comprehensive evaluation of the vascularization pattern and efficiency of biomaterials. Being compliant with the 3R-principles (replacement, reduction and refinement), the well-established and easy-to-handle CAM model offers many advantages such as low costs, immune-incompetence and short experimental times with high-grade read-outs when compared to conventional animal models. Therefore, combined with our imaging-guided approach it represents a powerful tool to study angiogenesis in biomaterials.

It is a challenge to develop multifunctional theranostic agents in one molecule, which simultaneously possesses tumor imaging ability with a high signal-to-noise ratio and excellent therapeutic activity. In this work, we synthesized and screened a series of BODIPY (BDP) with various absorption and fluorescence. The interplay of the molecular structure, pH-sensitive absorption and emission, and photodynamic and photothermal activities was well studied in detail. Photoinduced electron transfer, intramolecular charge transfer, and heavy atom effect were leveraged to engineer BDP with tumor imaging and therapeutic functions. The BDP nanoparticle formulations possessed multifunctional biological features, including selective treatment of cancer cells, near-infrared fluorescence, photoacoustic and computed tomography imaging, and photodynamic and photothermal therapy, as validated by cellular and animal experiments. These results not only give a new horizon to multifunctional BDP for biological applications but also show a new way to design the organic dye for tumor imaging and phototherapy.

Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance-ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function., Competing Interests: Conflict of interest statement: A.R.R. is the national principal investigator for the multiinstitutional trial of GSN-directed ablation, funded by Nanospectra Biosciences. He is also a consultant for Nanospectra Biosciences. J.L.W. and N.J.H. cofounded Nanospectra Biosciences in 2001 to transfer the photothermal therapeutics process from their labs into the clinic. They both have a small equity stake in this company but are not involved in any way with the company’s business or strategic decisions., (Copyright © 2019 the Author(s). Published by PNAS.)

Background: Multi-modal brain image registration is a prerequisite for accurate mapping of brain structure and function in neuroscience. Image registration is commonly performed using automated software; however, its accuracy decreases when images differ in modality, contrast, uniformity, and resolution. This limitation could be overcome by using an external reference point; however, high-contrast agents in multi-modal imaging have not been previously reported., New Methods: Here, we propose a novel multi-modal fiducial marker that contains Tungsten solution and provides high contrast in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). The basic characteristics of this multi-modal marker were investigated by assessing major sources of image contrast in the following modalities: density and T1-, T2-relaxivity in comparison with conventional contrast agents., Results: Tungsten solution had lower T1- and T2-relaxivity and high solubility, and showed high contrast in T1- and T2-weighted MR and CT images at a high-density concentration (˜3.0 g/mL), whereas other conventional solutions did not show sufficient contrast in either CT or MRI., Comparison With Existing Methods: The use of this Tungsten-based multi-modal marker allowed more accurate registration than a software-only method in phantom and animal experiments. Application of this method demonstrated accurate cortical surface mapping of neurotransmitter function (dopamine transporter, DAT) using PET and MRI, and provided a neurobiologically relevant cortical distribution consistent with previous literature on histology-based DAT immunoreactivity., Conclusions: The Tungsten-based multi-modal fiducial marker is non-radioactive, easy to handle, and aids precise registration across different modalities of brain imaging., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Polyvinyl chloride (PVC) is a commonly used tissue-mimicking material (TMM) for phantom construction using 3D printing technology. PVC-based TMMs consist of a mixture of PVC powder and dioctyl terephthalate as a softener. In order to allow the clinical use of a PVC-based phantom use across CT and magnetic resonance imaging (MRI) imaging platforms, we evaluated the mechanical and physical imaging characteristics of ten PVC samples. The samples were made with different PVC-softener ratios to optimize phantom bioequivalence with physiologic human tissue. Phantom imaging characteristics, including computed tomography (CT) number, MRI relaxation time, and mechanical properties (e.g., Poisson's ratio and elastic modulus) were quantified. CT number varied over a range of approximately -10 to 110 HU. The relaxation times of the T1-weighted and T2-weighted images were 206.81 ± 17.50 and 20.22 ± 5.74 ms, respectively. Tensile testing was performed to evaluate mechanical properties on the three PVC samples that were closest to human tissue. The elastic moduli for these samples ranged 7.000-12.376 MPa, and Poisson's ratios were 0.604-0.644. After physical and imaging characterization of the various PVC-based phantoms, we successfully produced a bioequivalent phantom compatible with multimodal imaging platforms for machine calibration and image optimization/benchmarking. By combining PVC with 3D printing technologies, it is possible to construct imaging phantoms simulating human anatomies with tissue equivalency., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Previously we have developed a first-generation PET insert prototype for small animal PET/MR imaging, which used resistor-based charge division multiplexing circuits and SensL B-series silicon photomultipliers (SiPMs). In this work we present results from a second-generation readout board with improved timing and count rate performance. Three detector boards were tested: the first-generation readout board with SensL SPMArray4B (SiPM-B), the second-generation readout board with SensL ArrayC-30035-16P-PCB (SiPM-C) using the 'fast' outputs for timing, and the second generation board using Hamamatsu S11361-3050AE-04 MPPC arrays. Timing data were obtained with detector modules in coincidence with a single-pixel SensL MicroFJ-SMA-30035 reference detector and acquired using standard NIM electronics, while count rate data were acquired using the OpenPET data acquisition electronics system. The full-width at half-maximum (FWHM) coincidence time resolution (CTR) for the SiPM-B, SiPM-C and MPPC designs were 2600  ±  200 ps, 550  ±  50 ps, and 570  ±  30 ps, respectively. OpenPET waveform capture determined the mean signal durations, measured as time above 10% of the maximum amplitude, were 1850  ±  150 ns, 600  ±  25 ns, and 350  ±  25 ns, respectively, where the short signal of the MPPC resulted in reduced pileup effects at higher count rates. Decaying source measurements showed a non-paralyzable dead time of 1.30-1.41 µs for all three detectors tested, which was limited by the signal capture and processing time of the OpenPET system.

Understanding the relationship between intracellular motion and macromolecular structure remains a challenge in biology. Macromolecular structures are assembled from numerous molecules, some of which cannot be labeled. Most techniques to study motion require potentially cytotoxic dyes or transfection, which can alter cellular behavior and are susceptible to photobleaching. Here we present a multimodal label-free imaging platform for measuring intracellular structure and macromolecular dynamics in living cells with a sensitivity to macromolecular structure as small as 20 nm and millisecond temporal resolution. We develop and validate a theory for temporal measurements of light interference. In vitro, we study how higher-order chromatin structure and dynamics change during cell differentiation and ultraviolet (UV) light irradiation. Finally, we discover cellular paroxysms, a near-instantaneous burst of macromolecular motion that occurs during UV induced cell death. With nanoscale sensitive, millisecond resolved capabilities, this platform could address critical questions about macromolecular behavior in live cells.

Coherent anti-Stokes Raman scattering (CARS) and second harmonic generation (SHG) are non-linear techniques that allow label-free, non-destructive and non-invasive imaging for cellular and tissue analysis. Although live-imaging studies have been performed previously, concerns that they do not cause any changes at the molecular level in sensitive biological samples have not been addressed. This is important especially for stem cell differentiation and tissue engineering, if CARS/SHG microscopy is to be used as a non-invasive, label-free tool for assessment of the developing neo-tissue. In this work, we monitored the differentiation of human fetal-femur derived skeletal cells into cartilage in three-dimensional cultures using CARS and SHG microscopy and demonstrate the live-imaging of the same developing neo-tissue over time. Our work conclusively establishes that non-linear label-free imaging does not alter the phenotype or the gene expression at the different stages of differentiation and has no adverse effect on human skeletal cell growth and behaviour. Additionally, we show that CARS microscopy allows imaging of different molecules of interest, including lipids, proteins and glycosaminoglycans, in the bioengineered neo-cartilage. These studies demonstrate the label-free and truly non-invasive nature of live CARS and SHG imaging and their value and translation potential in skeletal research, regeneration medicine and tissue engineering.

Advances in imaging instrumentation and technology have greatly contributed to nuclear cardiology. Dedicated cardiac SPECT cameras incorporating novel, highly efficient detector, collimator, and system designs have emerged with the expansion of nuclear cardiology. Solid-state radiation detectors incorporating cadmium zinc telluride, which directly convert radiation to electrical signals and yield improved energy resolution and spatial resolution and enhanced count sensitivity geometries, are increasingly gaining favor as the detector of choice for application in dedicated cardiac SPECT systems. Additionally, hybrid imaging systems in which SPECT and PET are combined with X-ray CT are currently widely used, with PET/MRI hybrid systems having also been recently introduced. The improved quantitative SPECT/CT has the potential to measure the absolute quantification of myocardial blood flow and flow reserve. Rapid development of silicon photomultipliers leads to enhancement in PET image quality and count rates. In addition, the reduction of emission-transmission mismatch artifacts via application of accurate time-of-flight information, and cardiac motion de-blurring aided by anatomical images, are emerging techniques for further improvement of cardiac PET. This article reviews recent advances such as these in nuclear cardiology imaging instrumentation and technology, and the corresponding diagnostic benefits.

Purpose: To design a spine phantom suitable for fusion of MR neurography (MRN) with interventional flat panel computed tomography (FPCT) images from tissue-equivalent agarose gels and artificial nerves in MRI, including material with equal attenuation to bone in computed tomography (CT)., Methods: T1-/T2-relaxation times of target tissue were determined in vivo (n = 5) using MR mapping-techniques. Serial dilution of castor oil lipogels was performed ex vivo in order to define correct composition for tissue-equivalent relaxation times. Similarly, serial dilution series of calcium carbonate (CaCO 3 ) and barium sulphate (BaSO 4 ) in synthetic resin were used to adjust radiodensity of selected vertebral bodies (L1-L5) and sacrum in CT. Nerve tissue was simulated with agarose-impregnated polyethylene fibers. Spine phantom was assembled using respective components in anthropomorphic geometry. A fat-saturated, T2-weighted 3D SPACE STIR sequence was acquired for MRN and subsequently fused with an on-site FPCT scan of the phantom., Results: In vivo T1-/T2-values for fat tissue were found to be at 394 ± 16 ms and 161 ± 16 ms, corresponding to a castor oil concentration of 50%. Analogously, bone marrow-equivalent values were measured at 822 ± 21 ms and 67 ± 6 ms, simulated with 40% castor oil. Cortical bone-like radiodensity of 1'115 ± 80 HU was achieved for artificial bone with 30% CaCO 3 and 1.5% BaSO 4 . Simulated nerves were successfully depicted in MRN and fused with FPCT, combining optimal contrasts for nerves and bones on-site., Conclusions: The customized phantom showed analogous tissue contrasts to in vivo conditions in both MRN and FPCT, facilitating simulations of fusion-image guided spine interventions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Fusion imaging with nuclear medicine and ultrasound via mobile handheld gamma cameras has been recently introduced, however a phantom for the registration accuracy of this fusion approach is still lacking. We developed a hybrid phantom, consisting of poly-methyl methacrylate and exchangeable ultrasound (US) compatible windows made of silicone or poly-vinyl chloride. A standard balloon catheter, filled with a mixture of [99mTc]TcO 4 and water, was positioned at the center of the water-filled phantom. This approach enabled an objective measurement of the registration accuracy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Organic/inorganic nanohybrids have attracted widespread interests due to their favorable properties and promising applications in biomedical areas. Great efforts have been made to design and fabricate versatile nanohybrids. Among different organic components, diverse polymers offer unique avenues for multifunctional systems with collective properties. This review focuses on the design, properties, and biomedical applications of organic/inorganic nanohybrids fabricated from inorganic nanoparticles and polymers. We begin with a brief introduction to a variety of strategies for the fabrication of functional organic/inorganic nanohybrids. Then the properties and functions of nanohybrids are discussed, including properties from organic and inorganic parts, synergistic properties, morphology-dependent properties, and self-assembly of nanohybrids. After that, current situations of nanohybrids applied for imaging, therapy, and imaging-guided therapy are demonstrated. Finally, we discuss the prospect of organic/inorganic nanohybrids and highlight the challenges and opportunities for the future investigations.

Purpose: An "RF-penetrable" PET insert that allows the MR body coil to be used for RF transmission was developed to make it easier for an existing MR center to achieve simultaneous PET/MRI. This study focuses on experiments and analyses to study PET/RF coil configurations for simultaneous PET/MR studies., Methods: To investigate the appropriate RF coil design, a transmit/receive (TX/RX) birdcage coil and an RX-only phased-array coil (TX from body coil), both fitting inside the PET ring were built and characterized. For MR performance evaluation, B 1 field uniformity and MR image SNR were calculated. PET photon attenuation due to each coil was studied by means of CT-based attenuation maps and reconstructed PET images., Results: When using the RX-only phased-array coil (TX from body coil), compared with the TX/RX birdcage coil, the B 1 field uniformity and the MR image (gradient echo and fast spin echo) SNR increased by 2.4±4.8%, 386.1±62.3%, and 205.0±56.5%, respectively. Although some components of the coil were distributed within the PET FOV, no significant PET photon attenuation was shown in the CT-based attenuation map and reconstructed PET images., Conclusion: RF coil configurations for an RF-penetrable PET insert for simultaneous PET/MRI were studied. The RX-only phased-array coil (TX from body coil) outperformed the TX/RX birdcage coil with improved MR performance as well as negligible PET photon attenuation., (© 2018 International Society for Magnetic Resonance in Medicine.)

Multiparametric quantitative imaging is gaining increasing interest due to its widespread advantages in clinical applications. Magnetic resonance fingerprinting is a recently introduced approach of fast multiparametric quantitative imaging. In this article, magnetic resonance fingerprinting acquisition, dictionary generation, reconstruction, and validation are reviewed., (© International Society for Magnetic Resonance in Medicine.)

This chapter describes methods for preparing samples of bone and bone cells for scanning electron microscopy (SEM). Backscattered electron (BSE) imaging is by far the most useful in the bone field, followed by secondary electrons (SE) and the energy dispersive X-ray (EDX) analytical modes. Samples may have 3D detail in a 3D surface, or be topography-free, polished or micromilled, resin-embedded block surfaces, or resin casts of space compartments surrounded by bone matrix. Methods for cells include fixation, drying, looking at undersides of bone cells, and metallic conductive coating. Maceration with alkaline bacterial pronase, hypochlorite, hydrogen peroxide, and sodium or potassium hydroxide to remove cells and unmineralized matrix is described in detail. Attention is given especially to methods for 3D BSE SEM imaging of bone samples. Recommendations are made for the types of resin embedding for BSE SEM imaging. Correlated confocal and SEM imaging of PMMA embedded bone requires the use of glycerol to coverslip. Cathodoluminescence (CL) mode SEM imaging is an alternative for visualizing fluorescent mineralizing front labels such as calcein and tetracyclines. Making spatial casts from PMMA or other resin-embedded samples is an important use of this material. Correlation with other imaging means, including microradiography and microtomography is important. Shipping wet bone samples between labs is best done in glycerol. Control of the vacuum pressure in the SEM sample chamber (now generally available) can be used to eliminate "charging" problems which were common, for example, with large, complex, cancellous bone samples.

Preclinical positron emission tomography, combined with magnetic resonance imaging (PET/MRI), is increasingly used as a tool to simultaneously characterize functional processes in vivo. Many emerging preclinical applications, however, are limited by PET detection sensitivity, especially when generating short imaging frames for quantitative studies. One such application is dynamic multifunctional imaging, which probes multiple aspects of a biological process, using relationships between the datasets to quantify interactions. These studies have limited accuracy due to the relatively low sensitivity of modern preclinical PET/MRI systems. The goal of this project is to develop a preclinical PET/MRI insert with detection sensitivity above 15% (250-750 keV) to improve quantitation in dynamic PET imaging. To achieve this sensitivity, we have developed a detector module incorporating a 2 cm thick crystal block, which will be arranged into a system with 8 cm axial FOV, targeting mice and rats. To maintain homogenous spatial resolution, the detector will incorporate dual-ended depth-of-interaction (DOI) encoding with silicon photomultiplier (SiPM) based photodetector arrays. The specific aim of this work is to identify a detector configuration with adequate performance for the proposed system. We have optimized the SiPM array geometry and tested two crystal array materials with pitch ranging from 0.8 to 1.2 mm and various surface treatments and reflectors. From these configurations, we have identified the best balance between crystal separation, energy resolution, and DOI resolution. The final detector module uses two rectangular SiPM arrays with 5  ×  6 and 5  ×  4 elements. The photodetector arrays are coupled to a 19  ×  19 array of 1 mm pitch LYSO crystals with polished surfaces and a diffuse reflector. The prototype design has 14.3%  ±  2.9% energy resolution, 3.57  ±  0.88 mm DOI resolution, and resolves all elements in the crystal array, giving it sufficient performance to serve as the basis for the proposed high sensitivity PET/MRI insert.

Positron emission tomography (PET)-magnetic resonance (MR) or single photon emission computed tomography (SPECT)-MR hybrid imaging is being used in daily clinical practice. Due to its advantages over stand-alone PET, SPECT or MR imaging, in many areas such as oncology, the demand for hybrid imaging techniques is increasing dramatically. The use of multimodal imaging probes or biomarkers in a single molecule or particle to characterize the imaging subjects such as disease tissues certainly provides us with more accurate diagnosis and promotes therapeutic accuracy. A limited number of multimodal imaging probes are being used in preclinical and potential clinical investigations. The further development of multimodal PET-MR and SPECT-MR imaging probes includes several key elements: novel synthetic strategies, high sensitivity for accurate quantification and high anatomic resolution, favourable pharmacokinetic profile and target-specific binding of a new probe. This review thoroughly summarizes all recently available and noteworthy PET-MR and SPECT-MR multimodal imaging probes including small molecule bimodal probes, nano-sized bimodal probes, small molecular trimodal probes and nano-sized trimodal probes. To the best of our knowledge, this is the first comprehensive overview of all PET-MR and SPECT-MR multimodal probes. Since the development of multimodal PET-MR and SPECT-MR imaging probes is an emerging research field, a selection of 139 papers were recognized following the literature review. The challenges for designing multimodal probes have also been addressed in order to offer some future research directions for this novel interdisciplinary research field., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Head motion occurring during brain PET studies leads to image blurring and to bias in measured local quantities. The objective of this work was to implement a correction method for PET data acquired with the mMR synchronous PET/MR scanner. Methods: A list-mode-based motion-correction approach has been designed. The developed rebinner chronologically reads the recorded events from the Siemens list-mode file, applies the estimated geometric transformations, and frames the detected counts into sinograms. The rigid-body motion parameters were estimated from an initial dynamic reconstruction of the PET data. We then optimized the correction for 11 C-Pittsburgh compound B ( 11 C-PIB) scans using simulated and actual data with well-controlled motion. Results: An efficient list-mode-based motion correction approach has been implemented, fully optimized, and validated using simulated and actual PET data. The average spatial resolution loss induced by inaccuracies in motion parameter estimates and by the rebinning process was estimated to correspond to a 1-mm increase in full width at half maximum with motion parameters estimated directly from the PET data with a temporal frequency of 20 s. The results show that the rebinner can be safely applied to the 11 C-PIB scans, allowing almost complete removal of motion-induced artifacts. The application of the correction method to a large cohort of 11 C-PIB scans led to the following observations: first, that more than 21% of the scans were affected by motion greater than 10 mm (39% for subjects with Mini-Mental State Examination scores below 20), and second, that the correction led to quantitative changes in Alzheimer-specific cortical regions of up to 30%. Conclusion: The rebinner allows accurate motion correction at a cost of minimal resolution reduction. Application of the correction to a large cohort of 11 C-PIB scans confirmed the necessity of systematically correcting for motion to obtain quantitative results., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: This study aims to develop, implement, and evaluate a dual-tuned 13 C/ 1 H head coil for integrated positron emission tomography/magnetic resonance (PET/MR) neuroimaging. The radiofrequency (RF) head coil is designed for optimized MR imaging performance and PET transparency and attenuation correction (AC) is applied for accurate PET quantification., Material and Methods: A dual-tuned 13 C/ 1 H RF head coil featuring a 16-rung birdcage was designed to be used for integrated PET/MR hybrid imaging. While the open birdcage design can be considered inherently PET transparent, all further electronic RF components were placed as far as possible outside of the field-of-view (FOV) of the PET detectors. The RF coil features a rigid geometry and thin-walled casing. Attenuation correction of the RF head coil is performed by generating and applying a dedicated 3D CT-based template attenuation map (μmap). Attenuation correction was systematically evaluated in phantom experiments using a large-volume cylindrical emission phantom filled with 18-F-Fluordesoxyglucose (FDG) radiotracer. The PET/MR imaging performance and PET attenuation correction were then evaluated in a patient study including six patients., Results: The dual-tuned RF head coil causes a mean relative attenuation difference of 8.8% across the volume of the cylindrical phantom, while the local relative differences range between 1% and 25%. Applying attenuation correction, the relative difference between the two measurements with and without RF coil is reduced to mean value of 0.5%, with local differences of ±3.6%. The quantitative results of the phantom measurements were corroborated by patient PET/MR measurements. Patient scans using the RF head coil show a decrease of PET signal of 5.17% ± 0.81% when compared to the setup without RF head coil in place, which served as a reference scan. When applying attenuation correction of the RF coil in the patient measurements, the mean difference to a measurement without RF coil was reduced to -0.87% ± 0.65%., Conclusion: A dual-tuned 13 C/ 1 H RF head coil was designed and evaluated regarding its potential use in integrated PET/MR hybrid imaging. Attenuation correction was successfully applied. In conclusion, the RF head coil was successfully integrated into PET/MR hybrid imaging and can now be used for 13 C/ 1 H multinuclear hybrid neuroimaging in future studies., (© 2018 American Association of Physicists in Medicine.)