Multimodal Imaging Brain Markers in Early Adolescence Are Linked with a Physically Active Lifestyle.

The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7 d physical activity, body mass index, heart rate, and blood pressure. Using canonical correlation analysis, we unravel a latent mode of brain-physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater gray matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence.SIGNIFICANCE STATEMENT An active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents' level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging-derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain-body relationships in an effort to foster brain health at this crucial stage in development.

Retinal disease in the neurology clinic.

PURPOSE OF REVIEW: Retinal disease can manifest with visual symptoms similar to those which result from central nervous system disorders. We provide a framework for considering retinal causes of common visual complaints presenting to a neurology clinic. RECENT FINDINGS: Technological advances have afforded quicker detection and a more thorough understanding of these retinal entities and are crucial to consider when evaluating visual complaints in the neurology clinic. SUMMARY: It is essential to maintain a working knowledge of common retinal conditions that symptomatically overlap with common neurologic conditions. Furthermore, the ophthalmoscopic exam and retinal imaging modalities can both aid in the diagnosis and workup of visual complaints and neurologic disease.

Updates on ophthalmic imaging features of optic disc drusen, papilledema, and optic disc edema.

PURPOSE OF REVIEW: Optic nerve head elevation can be associated with vision loss. This review provides an update regarding key features of optic disc drusen (ODD) compared with papilledema from increased intracranial pressure and optic disc edema from other causes. RECENT FINDINGS: Clinical history and funduscopic examination are not sufficient to correctly diagnose different causes of optic nerve head elevation. Multimodal ophthalmic imaging is noninvasive and should be used as first-line diagnostic testing to distinguish optic disc edema or papilledema from pseudoedema. Advanced ophthalmic imaging, including enhanced depth imaging optical coherence tomography (EDI-OCT) and autofluorescence imaging, can visualize ODD at high resolution and determine whether there is optic disc edema. OCT angiography does not require contrast and can rapidly visualize papillary, peripapillary, and macular microvasculature and identify important vascular biomarker of ischemia and, potentially, visual prognosis. SUMMARY: Multimodal ophthalmic imaging can help in the diagnosis of ODD and optic disc edema and identify patients at high risk of vision loss and neurological issues in order to ensure appropriate diagnosis and treatment.

Current Status and Future of BI-RADS in Multimodality Imaging, From the AJR Special Series on Radiology Reporting and Data Systems.

BI-RADS is a communication and data tracking system that has evolved since its inception as a brief mammography lexicon and reporting guide into a robust structured reporting platform and comprehensive quality assurance tool for mammography, ultrasound, and MRI. Consistent and appropriate use of the BI-RADS lexicon terminology and assessment categories effectively communicates findings, estimates the risk of malignancy, and provides management recommendations to patients and referring clinicians. The impact of BI-RADS currently extends internationally through six language translations. A condensed version has been proposed to facilitate a phased implementation of BI-RADS in resource-constrained regions. The primary advance of the 5th edition of BI-RADS is harmonization of the lexicon terms across mammography, ultrasound, and MRI. Harmonization has also been achieved across these modalities for the reporting structure, assessment categories, management recommendations, and data tracking system. Areas for improvement relate to certain common findings that lack lexicon descriptors and a need for further clarification of proper use of category 3. BI-RADS is anticipated to continue to evolve for application to a range of emerging breast imaging modalities.

(An overview of) Synergistic reconstruction for multimodality/multichannel imaging methods.

Imaging is omnipresent in modern society with imaging devices based on a zoo of physical principles, probing a specimen across different wavelengths, energies and time. Recent years have seen a change in the imaging landscape with more and more imaging devices combining that which previously was used separately. Motivated by these hardware developments, an ever increasing set of mathematical ideas is appearing regarding how data from different imaging modalities or channels can be synergistically combined in the image reconstruction process, exploiting structural and/or functional correlations between the multiple images. Here we review these developments, give pointers to important challenges and provide an outlook as to how the field may develop in the forthcoming years. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'.

Future Challenges of Multimodality Imaging.

During the last decade, positron emission tomography/computed tomography (PET/CT) and single-photon emission computed tomography/computed tomography (SPECT/CT) have procured advances in research and clinical application of fusion imaging. The recent introduction of digital PET/CT opens new horizons for multimodality molecular imaging. This system offers more precise, simultaneous morphologic, functional, and molecular information of a living system. Moreover, other combinations of anatomic and functional imaging modalities hold promise in basic medical research or in clinical medicine. These developments are paralleled by advances in the field of biomolecules and particles that will provide new agents useful for more than one imaging modality and will facilitate the study of the same target by different imaging devices. Digital PET/CT may emerge as a powerful multimodality technique with great clinical impact on the diagnosis and therapy assessment of oncological diseases due to its enhanced sensitivity.

Multimodality imaging: Bird's eye view from the 2019 American College of Cardiology Scientific Sessions.

The 2019 American College of Cardiology Scientific Sessions displayed innovation in many areas for the evaluation and management of cardiovascular disease from preventive evaluation and care to advanced interventions. Imaging played a central role in these developments with a highlight of the conference being the imaging research presented. This review will summarize key imaging studies which were presented at this scientific meeting which will lead to innovation in the evaluation and management of cardiovascular disease. Experts in nuclear imaging (DW/MA), echocardiography (MS), cardiac magnetic resonance (SL), and cardiac computed tomography (RB) selected abstracts which they found to be of particular interest to the multimodality imaging audience and were integrated into this review (LP).

Theranostics in Nuclear Medicine: Emerging and Re-emerging Integrated Imaging and Therapies in the Era of Precision Oncology.

Theranostics refers to the pairing of diagnostic biomarkers with therapeutic agents that share a specific target in diseased cells or tissues. Nuclear medicine, particularly with regard to applications in oncology, is currently one of the greatest components of the theranostic concept in clinical and research scenarios. Theranostics in nuclear medicine, or nuclear theranostics, refers to the use of radioactive compounds to image biologic phenomena by means of expression of specific disease targets such as cell surface receptors or membrane transporters, and then to use specifically designed agents to deliver ionizing radiation to the tissues that express these targets. The nuclear theranostic approach has sparked increasing interest and gained importance in parallel to the growth in molecular imaging and personalized medicine, helping to provide customized management for various diseases; improving patient selection, prediction of response and toxicity, and determination of prognosis; and avoiding futile and costly diagnostic examinations and treatment of many diseases. The authors provide an overview of theranostic approaches in nuclear medicine, starting with a review of the main concepts and unique features of nuclear theranostics and aided by a retrospective discussion of the progress of theranostic agents since early applications, with illustrative cases emphasizing the imaging features. Advanced concepts regarding the role of fluorine 18-fluorodeoxyglucose PET in theranostics, as well as developments in and future directions of theranostics, are discussed. ©RSNA, 2020 See discussion on this article by Greenspan and Jadvar.

Longitudinal multimodal imaging and clinical endpoints for frontotemporal dementia clinical trials.

Frontotemporal dementia refers to a group of progressive neurodegenerative syndromes usually caused by the accumulation of pathological tau or TDP-43 proteins. The effects of these proteins in the brain are complex, and each can present with several different clinical syndromes. Clinical efficacy trials of drugs targeting these proteins must use endpoints that are meaningful to all participants despite the variability in symptoms across patients. There are many candidate clinical measures, including neuropsychological scores and functional measures. Brain imaging is another potentially attractive outcome that can be precisely quantified and provides evidence of disease modification. Most imaging studies in frontotemporal dementia have been cross-sectional, and few have compared longitudinal changes in cortical volume with changes in other measures such as perfusion and white matter integrity. The current study characterized longitudinal changes in 161 patients with three frontotemporal dementia syndromes: behavioural variant frontotemporal dementia (n = 77) and the semantic (n = 45) and non-fluent (n = 39) variants of primary progressive aphasia. Visits included comprehensive neuropsychological and functional assessment, structural MRI (3 T), diffusion tensor imaging, and arterial spin labelled perfusion imaging. The goal was to identify measures that are appropriate as clinical trial outcomes for each group, as well as those that might be appropriate for trials that would include more than one of these groups. Linear mixed effects models were used to estimate changes in each measure, and to examine the correlation between imaging and clinical changes. Sample sizes were estimated based on the observed effects for theoretical clinical trials using bootstrapping techniques to provide 95% confidence intervals for these estimates. Declines in functional and neuropsychological measures, as well as frontal and temporal cortical volumes and white matter microstructure were detected in all groups. Imaging changes were statistically significantly correlated with, and explained a substantial portion of variance in, the change in most clinical measures. Perfusion and diffusion tensor imaging accounted for variation in clinical decline beyond volume alone. Sample size estimates for atrophy and diffusion imaging were comparable to clinical measures. Corpus callosal fractional anisotropy led to the lowest sample size estimates for all three syndromes. These findings provide further guidance on selection of trial endpoints for studies in frontotemporal dementia and support the use of neuroimaging, particularly structural and diffusion weighted imaging, as biomarkers. Diffusion and perfusion imaging appear to offer additional utility for explaining clinical change beyond the variance explained by volume alone, arguing for considering multimodal imaging in treatment trials.

The clinical spectrum of Fontan-associated liver disease: results from a prospective multimodality screening cohort.

AIMS: Liver fibrosis and cirrhosis are a consequence of a Fontan physiology, and determine prognosis. It is unclear whether non-invasive assessment of liver pathology is helpful to provide clinically relevant information. The aims of this study were to assess the spectrum of Fontan-associated liver disease (FALD) and usefulness of non-invasive methods to assess biopsy confirmed liver fibrosis. METHODS AND RESULTS: Hepatic screening of consecutive patients consisted of a blood panel, ultrasonography, elastography, contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) scan, and liver biopsy (scored with Fontan specific fibrosis scores and collagen proportionate area; CPA). Fibrosis parameters, varices, ascites, and splenomegaly were measured on imaging. Thirty-eight of 49 referred patients (27 ± 6.6 years, 73.7% male) underwent the complete screening protocol. Liver fibrosis on biopsy was present in all patients, and classified as severe (Stages 3-4) in 68%. Median CPA was 22.5% (16.9-29.5) and correlated with individual fibrosis scores. ELF® and liver stiffness were elevated, but MELD-XI scores were low in all patients. Fibrosis severity neither correlated to ELF® and liver stiffness, nor to (semi-) quantitative fibrosis parameters on MRI/CT. Varices were present in 50% and hyperenhancing nodules in 25% of patients, both independent of fibrosis stage, but varices were associated with higher CPA values. CONCLUSION: The FALD spectrum includes both hepatic congestion and severe fibrosis, with signs of portal hypertension and hyperenhancing nodules as significant manifestations. Routine imaging, transient elastography, and serum biomarkers are unable to accurately assess severity of liver fibrosis in this cohort. Future research should focus on validating new diagnostic tools with biopsy as the reference standard.

[Hybrid imaging in prostate cancer : Status quo and future applications]. / Hybridbildgebung beim Prostatakarzinom : Status quo und zukünftige Entwicklungen.

BACKGROUND: Recently, the use of prostate-specific membrane antigen (PSMA) tracers like 68Ga-PSMA-11 in positron emission tomography (PET) have shown promising results and are helping to improve care for patients with prostate cancer (PC). PURPOSE: In the following we review the current literature on PSMA-ligand PET, in particular with regard to the currently increasing replacement of 68Ga-PSMA ligands by 18F-labeled PSMA ligands. RESULTS: PSMA-ligand PET is most frequently used for biochemical recurrence. Here, 68Ga-PSMA-11 PET/CT shows superior detection rates compared to conventional imaging modalities, especially in small, morphologically unsuspicious lesions, even at low PSA values. Furthermore, 68Ga-PSMA PET imaging seems to be an encouraging alternative for staging of high-risk patients, particularly in combination with multiparametric MRI. CONCLUSION: The use of PSMA-ligand PET has revolutionized PC imaging. Thus, PSMA-ligand PET is expected to play an even greater role in PC diagnostics in the future, especially as 18F-labeled PSMA ligands are now increasingly used. However, simultaneous image analysis of PET and CT as well as a differentiated image evaluation (clinical context, knowledge of common pitfalls) is mandatory.

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling.

Aging is characterized by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesize, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n = 102, age range = 30-89 years) with MRI and Aß PET data, we estimated age-related cortical thinning, hippocampal atrophy and Aß deposition. In addition to carrying out surface-based morphological and metabolic mapping experiments, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased Aß deposition occurred across the entire cortical topography, increased Aß deposition was especially pronounced toward higher-order transmodal regions. Age-related atrophy was greater toward the posterior end of the hippocampal long-axis. No significant effect of age on Aß deposition in the hippocampus was observed. Imaging markers correlated with behavioral measures of fluid intelligence and episodic memory in a topography-specific manner, confirmed using both univariate as well as multivariate analyses. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyze and conceptualize brain-based biomarkers of aging.

Diffusion-weighted imaging and diffusion tensor imaging as adjuncts to conventional MRI for the diagnosis and management of peripheral nerve sheath tumors: current perspectives and future directions.

Peripheral nerve sheath tumors (PNSTs) account for ~ 5% of soft tissue neoplasms and are responsible for a wide spectrum of morbidities ranging from localized neuropathy to fulminant metastatic spread and death. MR imaging represents the gold standard for identification of these neoplasms, however, current anatomic MR imaging markers do not reliably detect or differentiate benign and malignant lesions, and therefore, biopsy or excision is required for definitive diagnosis. Diffusion-weighted MR imaging (DWI) serves as a useful tool in the evaluation and management of PNSTs by providing functional information regarding the degree of diffusion, while diffusion tensor imaging (DTI) aids in determining the directional information of predominant diffusion and has been shown to be particularly useful for pre-operative planning of these tumors by delineating healthy and pathologic fascicles. The article focuses on these important neurogenic lesions, highlighting the current utility of diffusion MR imaging and future directions including computerized radiomic analysis. KEY POINTS: • Anatomic MRI is moderately accurate in differentiating benign from malignant PNST. • Diffusion tensor imaging facilitates pre-operative planning of PNSTs by depicting neuropathy and tractography. • Radiomics will likely augment current observer-based diagnostic criteria for PNSTs.

Functional and Anatomical Imaging in Patients with Ischemic Symptoms and Known Coronary Artery Disease.

PURPOSE OF REVIEW: This review is aimed at summarizing recent advances in functional, anatomical, and hybrid imaging techniques used in the assessment of ischemic complaints in patients with known coronary artery disease (CAD). RECENT FINDINGS: Cardiovascular imaging has seen significant growth over the last decade in the fields of coronary computed tomography angiography (CCTA), FFR derived from CCTA, cardiac magnetic resonance, radionuclide myocardial perfusion imaging, and hybrid imaging for the purposes of evaluating symptoms concerning for ischemia. This growth stems from refinement of imaging techniques and hardware and software advances that have made current techniques more accurate with less acquisition time. However, every anatomic and functional imaging modality has important technical and patient-specific limitations. This review assesses these issues, guides a patient-centered imaging approach, and identifies important research questions to resolve. Recent advances in non-invasive cardiovascular imaging can provide important information in patients with known CAD beyond traditional imaging techniques; the use of these novel tools refines the clinical management of complex patients with ischemic symptoms and known CAD.

Radiation dose in nuclear medicine: the hybrid imaging.

Hybrid imaging procedures such as single-photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT) showed a rapid diffusion in recent years because of their high sensitivity, specificity, and accuracy, due to a more accurate localization and definition of scintigraphic findings. However, hybrid systems inevitably lead to an increase in patient radiation exposure because of the added CT component. Effective doses due to the radiopharmaceuticals can be estimated by multiplying the administered activities by the effective dose coefficients, while for the CT component the dose-length product can be multiplied by a conversion coefficient k. However, the effective dose value is subject to a high degree of uncertainty and must be interpreted as a broad, generic estimate of biologic risk. Although the effective dose can be used to estimate and compare the risk of radiation exposure across multiple imaging techniques, clinicians should be aware that it represents a generic evaluation of the risk derived from a given procedure to a generic model of the human body. It cannot be applied to a single individual and should not be used for epidemiologic studies or the estimation of population risks due to the inherent uncertainties and oversimplifications involved. Practical ways to reduce radiation dose to patients eligible for hybrid imaging involve adjustments to both the planning phase and throughout the execution of the study. These methods include individual justification of radiation exposure, radiopharmaceutical choice, adherence to diagnostic reference levels (DLR), patient hydration and bladder voiding, adoption of new technical devices (sensitive detectors or collimators) with new reconstruction algorithms, and implementation of appropriate CT protocols and exposure parameters.

Clinical PET/MRI: 2018 Update.

OBJECTIVE: The purpose of this article is to provide an update on clinical PET/MRI, including current and developing clinical indications and technical developments. CONCLUSION: PET/MRI is evolving rapidly, transitioning from a predominant research focus to exciting clinical practice. Key technical obstacles have been overcome, and further technical advances promise to herald significant advancements in image quality. Further optimization of protocols to address challenges posed by this hybrid modality will ensure the long-term success of PET/MRI.

New Imaging Markers for Movement Disorders.

PURPOSE OF REVIEW: For decades, identifying in vivo imaging biomarkers to accurately differentiate between various movement disorders as well as to understand their underlying pathophysiological abnormalities has been the aim of scientific work. Recent advances in multimodal imaging enable the visualization of structural and functional brain changes in these pathological conditions, thus raising the value of imaging techniques as powerful tools to improve sensitivity and specificity of clinical diagnoses. This article reviews well-established and recent developments in imaging markers for movement disorders. RECENT FINDINGS: Whereas several imaging approaches seem to be promising, many modalities are still under development and may not provide decisive answers. Thus, the use of combined imaging modalities as well as the acquisition of methodological consensus in the scientific community may provide more conclusive findings in the future of biomarkers. Although a single biomarker has yet not been identified, multiple markers derived from different imaging modalities may represent the right approach.

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology.

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

Multi-modality imaging: Bird's eye view from the 2016 American Heart Association Scientific Sessions.

This review summarizes key imaging studies that were presented in the American Heart Association Scientific Sessions 2016 related to the fields of nuclear cardiology, cardiac computed tomography, cardiac magnetic resonance, and echocardiography. This bird's eye view will inform readers about multiple studies from these different modalities. We hope that this general overview will be useful for those that did not attend the conference as well as to those that did since it is often difficult to get exposure to many abstracts at large meetings. The review, therefore, aims to help readers stay updated on the newest imaging studies presented at the meeting.

Cardiovascular PET/MR imaging: Quo Vadis?

With the recent advent of PET/MRI scanners, the combination of molecular imaging with a variety of known and novel PET radiotracers, the high spatial resolution of MRI, and its potential for multi-parametric imaging are anticipated to increase the diagnostic accuracy in cardiovascular disease detection, while providing novel mechanistic insights into the initiation and progression of the disease state. For the time being, cardiac PET/MRI emerges as potential clinical tool in the identification and characterization of infiltrative cardiac diseases, such as sarcoidosis, acute or chronic myocarditis, and cardiac tumors, respectively. The application of PET/MRI in conjunction with various radiotracer probes in the identification of the vulnerable atherosclerotic plaque also holds much promise but needs further translation and validation in clinical investigations. The combination of molecular imaging and creation of multi-parametric imaging maps with PET/MRI, however, are likely to set new horizons to develop predictive parameters for myocardial recovery and treatment response in ischemic and non-ischemic cardiomyopathy patients. Molecular imaging and multi-parametric imaging in cardiovascular disease with PET/MRI at current stage are at its infancy but bear a bright future.