Multimodal Imaging Research Articles

Tuberous sclerosis complex combined with primary lymphedema: A case report

Tuberous sclerosis complex combined with primary lymphedema: A case report

A Proposal of a New Tool for the Assessment of Damage in Behçet Syndrome Uveitis: Cerrahpasa Ocular Damage Grading System

ABSTRACT Introduction/Objective There is currently no tool available to assess the severity of damage in uveitis due to Behçet’s syndrome (BS). In this preliminary study, we developed a new grading system to evaluate ocular damage and assessed it in a prospective cohort. Methods A specialist in BS uveitis (YO) developed a grading system for ocular damage with five grades based on the extent of damage in the posterior segment. YO trained a senior and general ophthalmologist with sample fundus images. BS patients who had undergone color fundus photography during their routine visits in attack-free periods were included in the study. The color fundus photos of this prospective cohort were evaluated blindly by YO and his trainees using the new grading tool. Inter and intra-observer agreement between the graders were assessed by Cohen’s kappa analysis. The evaluation of YO was considered as the gold standard. Results One hundred eighty-five eyes of 108 (29 F/79 M) patients with BS uveitis were graded for damage by two investigators. Their mean age was 38,58 years and their median ocular disease duration was 13 years. The gold standard and the two investigators exhibited substantial concordance with the ocular damage grading system. The inter- and intra-observer agreement were also almost perfect. Conclusion The newly developed ocular damage grading system enables the standardization of damage severity in BS uveitis. It is imperative to conduct internal and external validations across diverse cohorts. Furthermore, future studies should investigate its correlation with other multimodal imaging methods such as fluorescein angiography and optical coherence tomography.

Secondary cardiac lymphoma presenting with cardiac tamponade and cardiac mass: a case report

BackgroundCardiac tamponade as the presenting manifestation of systemic lymphoma is relatively uncommon. Pericardium is the commonest site of involvement in secondary malignancies with systemic lymphoma involving the heart in 20% of the cases.Case presentationWe describe a case of a 78-year-old gentleman, who presented with symptoms of new onset cardiac failure, and hemodynamic compromise. An echocardiography revealed cardiac tamponade, necessitating an emergency pericardiocentesis. With the aid of multimodality imaging, he was found to have a right atrioventricular groove mass, widespread lymph node enlargement with bone and peritoneal involvement. Ultimately, a histopathological evaluation revealed a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL).ConclusionsOur case illustrates that a patient with DLBCL may present with cardiac tamponade as a result of metastasis. This diagnosis, although rare, is likely to be missed, which can cause fatal complications, such as cardiac tamponade, fatal arrhythmias or sudden cardiac death.

Active Targeting Hyaluronan Conjugated Nanoprobe for Magnetic Particle Imaging and Near-Infrared Fluorescence Imaging of Breast Cancer and Lung Metastasis.

A major contributing cause to breast cancer related death is metastasis. Moreover, breast cancer metastasis often shows little symptoms until a large area of the organs is occupied by metastatic cancer cells. Breast cancer multimodal imaging is attractive since it integrates advantages from several modalities, enabling more accurate cancer detection. Glycoprotein CD44 is overexpressed on most breast cancer cells and is the primary cell surface receptor for hyaluronan (HA). To facilitate breast cancer diagnosis, we report an indocyanine green (ICG) and HA conjugated iron oxide nanoparticle (NP-ICG-HA), which enabled active targeting to breast cancer by HA-CD44 interaction and detected metastasis with magnetic particle imaging (MPI) and near-infrared fluorescence imaging (NIR-FI). When evaluated in a transgenic breast cancer mouse model, NP-ICG-HA enabled the detection of multiple breast tumors in MPI and NIR-FI, providing more comprehensive images and a diagnosis of breast cancer. Furthermore, NP-ICG-HAs were evaluated in a lung metastasis model. Upon NP-ICG-HA administration, MPI showed clear signals in the lungs, indicating the tumor sites. This is the first time that HA-based NPs have enabled MPI of cancer. NP-ICG-HAs are an attractive platform for noninvasive detection of primary breast cancer and lung metastasis.

AN OUT OF HOSPITAL CARDIAC ARREST SURVIVOR WITH PRESUMED EMBOLIC MYOCARDIAL INFARCTION: ROLE OF MULTI–MODALITY IMAGING

Abstract Background Myocardial infarction with non–obstructive coronary arteries (MINOCA) refers to a puzzling clinical entity that is characterized by symptoms suggestive of acute coronary syndrome, demonstrates troponin elevation with inconclusive coronary angiogram. The underlying pathophysiologic mechanisms include atherosclerotic cause or non–atherosclerotic causes, such as coronary dissection or coronary embolus. A standardized approach that includes multimodality imaging is necessary to determine underlying aetiology and direct appropriate treatment. Case Summary A 57–year–old male was admitted to our hospital after experiencing cardiac arrest after physical exercise (swimming) treated immediately with cardiac pulmonary resuscitation and two defibrillator–delivered electrical shocks for shockable rhythm before return of spontaneous circulation. Relevant abnormal bloods included a hs–Troponin I elevation. Invasive coronary angiography demonstrated non–obstructed coronary arteries. Subsequent cardiac magnetic resonance imaging (MRI) demonstrated akinesia and an area of subendocardic late gadolinium enhancement in the inferior–lateral wall. This pattern was in keeping with an ischaemic cause, as a recent embolic myocardial infarction. Further investigations, including contrast bubble echocardiogram, were performed in order to identify a cause and source of the embolic infarction and led to the diagnosis of tunnel–like patent foramen ovale with right to left shunting, then confirmed on trans–oesophageal echocardiogram. The patient was treated as myocardial infarction most likely due to embolic phenomena in the presence of a PFO. Therefore, a transvenous ICD was implanted for secondary prevention and the patient underwent percutaneous closure of the PFO. Discussion and Conclusion MINOCA can occur in 5–15% of all acute coronary syndromes and represents a working diagnosis. It is important to identify the underlying aetiology of their presentation to appropriately manage them. In particular, where cardiac MRI demonstraded LGE areas ichaemic patterns, myocardial infarction due to secondary embolism should be considered and the next step in clinical management is to identify potential sources of emboli performing further assessments. Multi–modality imaging with cardiac MRI and echocardiogram (transthoracic, contrast bubble and trans–oesophageal) is important in correctly identifying any source of emboli and the diagnosis of any intra–cardiac shunt.

Spontaneous Thrombus Resolution in the Right Coronary Artery Stent: Sequential Multimodal Imaging Analysis

Abstract Despite previous reports indicating that in-stent tissue protrusion is not associated with worse clinical outcome, its natural history remains unclear. This is the first to describe the natural history of in-stent thrombus associated with tissue protrusion post-stenting, using multimodal imaging.

A RARE CASE OF TYPE A AORTIC DISSECTION PRESENTING AS ACUTE STROKE: A DIAGNOSTIC CHALLENGE

Abstract A 60–year–old woman presented to the emergency department with acute left hemiplegia, not chest pains. Past medical history was significant for family history of aortic aneurysm, arterial hypertension. At brain–CT was reported hypodensity areas in posterior arm of the right internal capsule and in right tempero–polar lobe, confirmed on brain–MRI, and compatible with acute ischemic injury. Echocolor–dopper of epiaortic vessels documentated ulcerated plaque into the right common carotid artery (CCA). Selective catheterization found focal dissection obstructing the flow, treated with self–expanding stent. On echocardiography evalutation for suspiction of TAAD: dilatation of ascending aorta with flap oscillation, severe arotic regurgitation, pericardial effusion (Fig. 1). CT–Angiography was performed with evidence of type A dissection extending superiorly to the right CCA and inferiorly to the iliac bifurcation. For coma state, the patient was mechanically ventilated, and seriate CTs showed new ischemic lesions and hemorrhagic infarction of previous. Because of contraindication for cardiac surgery due neurological state, the patient was referred at medical therapy as bridge to hybrid aortic arc substitution at resolution of intracranial hemorrhages. In the next days there was progressive improvement neurological status with restoration of sensory and autonomic breathing with hemodynamic stability. Aortic dissection (AD) is defined as a disruption of the medial layer leading to the formation of two lumens separated by an intimomedial flap. AD is a critical diagnosis to make due to life–threatening outcomes and its non–specific presentation as in the case of our patient where the management of AD was delayed due to an unusual initial clinical presentation. Multimodality imaging approach has been fundamental for correct diagnosis and risk stratification. A limited number of studies have reported cases with stroke as the first symptom with concomitant TAAD. Concomitant intracerebral hemorrhage and TAAD is a very rare presentation and the optimal timing of surgery in these patients is unknown. In our opinion, patients who presents acute stroke should be carefully evaluated using multimodal imaging to exclude TAAD before administering reperfusion therapy. In addition, performing CAS before surgery for TAAD is challenging but might be a valid treatment option to maintain good brain perfusion and improve prognosis, but further investigations are needed.

PATIENT WITH CHRONIC CORONARY SYNDROME: USE OF MULTIMODAL IMAGING FOR CORRECT DIAGNOSIS AND TREATMENT

Abstract In the context of CCS, CCTA allows us to discriminate with almost certainty between patients with the absence of disease. In case of a positive test, the characteristics of the plaque allow to stratified risk of developing future events. In doubtful cases it is necessary to resort to a multimodal imaging strategy for the correct diagnosis. We present the case of a 63-year-old hypertensive and dyslipidemic man who started presenting two months ago episodes of asthenia associated with tachycardia and jugular constriction after taking the usual CCB therapy. With a pre-test probability of 26%, a CCTA scan was requested which highlighted a non-calcific fibrous plaque (Image 1) at the level of the middle circumflex inducing a moderate stenosis (Cad-Rads 3). The patient underwent coronary angiography which confirmed this lesion and also highlighted a similar one downstream of the first. (Image 2) The OCT evaluation showed: 7 mm eccentric fibrous proximal plaque with evidence of multiple intimal layers (Healed plaque) in its distal third and with evidence of a medial-intimal flap involving three quadrants in the proximal two thirds (270°), with current intact endothelium and presence of neo-angiogenesis; MLA 2.33 mm² and AS 70%. Picture compatible with healed spontaneous dissection of the vessel. (Image 3) The subsequent 12 mm concentric plaque (360° involvement of the vessel) had a predominantly lipid component with macrophages and fibrous cap of 60 µm, MLA of 2.3mm² and AS 72%. Panel compatible with high risk plaque. (Image 4) It was decided to implant a 3.5x26mm drug-eluting stent through OCT-guided PCI with final MSA of 7.62 mm², stent expansion of 81%, absence of dissections at the edges and residual distal edge plaque with MLA of 7.6 mm². (Image 5). Conclusions Healed plaques are more frequent in patients with CCS and represent a plaque complicated by medial-intimal ulceration subsequently healed by neo-endothelialization. On CCTA they appear as non-calcific fibrous plaques with an intermediate density expressed in Hounsfield Units but the definitive diagnosis can only be obtained using an Intravascular Imaging method (OCT in the case presented). The patient appears asymptomatic after resuming his usual antihypertensive therapy at 30-day FU.

A "PARADOXICAL" MINOCA

Abstract Background The acronym MINOCA refers to myocardial infarction with normal or near–normal coronary arteries on invasive angiography. We report a case of MINOCA caused by paradoxical coronary embolism due to a right–to–left shunting through a patent fossa ovalis. Integrated multimodality imaging diagnostic work–up has been crucial for identifying the mechanism underlying MINOCA. Case Report A 48–year–old male was admitted to the Coronary Care Unit for sudden–onset oppressive chest pain lasting 1 hour, radiating to the left arm; no specific changes in ST–segment on a 12–lead ECG and elevated high–sensitive troponin I (peak value 1562 ng). Transthoracic echocardiography showed normal dimensions and function of the cardiac chambers and excluded valvular and pericardial diseases. Given the characteristics of the chest pain, we performed an urgent coronary angiography that showed normal epicardial coronary, including testing for epicardial coronary spasm and microvascular dysfunction. We also used Optical Coherence Tomography on LAD e RCA to rule out critical stenosis and sign of plaque instability. To investigate the etiology of myocardial damage the patient underwent a cardiac magnetic resonance (CMR) imaging that yielded the following findings: hypokinesis of the inferior–middle segment of the left ventricle associated myocardial edema and near transmural LGE. These features were consistent with a recent ischemic injury. Additionally, CMR showed an atrial septal aneurysm and a channel–like pattern of the interatrial septum, raising the suspicion of patent foramen ovale (PFO). The transesophageal echocardiography and transcranial Doppler with bubble test confirmed the presence of a PFO responsible for right–to–left shunting. Atrial fibrillation was excluded with ECG telemetry throughout the entire 7day hospitalization. Conclusions Based on the result of the overall clinical–instrumental evaluation, MINOCA caused by paradoxical coronary embolism due to a right–to–left shunting through a PFO was considered the most plausible diagnostic hypothesis. The patient underwent to interventional percutaneous closure of PFO and was discharged with no symptoms or complication at the follow–up.

Porphyrin-Based Self-Assembled Nanoparticles for PET/MR Imaging of Sentinel Lymph Node Metastasis.

Diagnosing of lymph node metastasis is challenging sometimes, and multimodal imaging offers a promising method to improve the accuracy. This work developed porphyrin-based nanoparticles (68Ga-F127-TAPP/TCPP(Mn) NPs) as PET/MR dual-modal probes for lymph node metastasis imaging by a simple self-assembly method. Compared with F127-TCPP(Mn) NPs, F127-TAPP/TCPP(Mn) NPs synthesized by amino-porphyrins (TAPP) doping can not only construct PET/MR bimodal probes but also improve the T1 relaxivity (up to 456%). Moreover, T1 relaxivity can be adjusted by altering the molar ratio of TAPP/TCPP(Mn) and the concentration of F127. However, a similar increase in T1 relaxivity was not observed in the F127-TCPP/TCPP(Mn) NPs, which were synthesized using carboxy-porphyrins (TCPP) doping. In a breast cancer lymph node metastasis mice model, subcutaneous injection of 68Ga-F127-TAPP/TCPP(Mn) NPs through the hind foot pad, the normal lymph nodes and metastatic lymph nodes were successfully distinguished based on the difference of PET standard uptake values and MR signal intensities. Furthermore, the dark brown F127-TAPP/TCPP(Mn) NPs demonstrated the potential for staining and mapping lymph nodes. This study provides valuable insights into developing and applying PET/MR probes for lymph node metastasis imaging.

Multimodal imaging findings of primary liver clear cell carcinoma: a case presentation

Primary clear cell carcinoma of liver (PCCCL) is a special and relatively rare subtype of hepatocellular carcinoma (HCC), which is more common in people over 50 years of age, with a preference for men and a history of hepatitis B or C and/or cirrhosis. Herein, we present a case of a 60-year-old woman who came to our hospital for medical help with right upper abdominal pain. The imaging examination showed a low-density mass in the right lobe of his liver. In contrast enhanced computed tomography (CT) or T1-weighted imaging, significant enhancement can appear around the tumor during the arterial phase, and over time, the degree of enhancement of the tumor gradually decreases. The lession showed obviously increased fluorine-18 fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/CT. These imaging findings contribute to the diagnosis of PCCCL and differentiate it from other types of liver tumors.

Central Serous Chorioretinopathy: Epidemiology, Genetics and Clinical Features.

Central serous chorioretinopathy (CSCR) is the fourth most common medical retinal disease. Moderate vision loss occurs in approximately one-third of patients who have the chronic form of the disease. CSCR has a multifactorial etiology, with acquired risk factors and increasing evidence of genetic susceptibility factors. The detection of new gene variants in CSCR and association of these variants with age-related macular degeneration provide insights into possible disease mechanisms. The contribution of multimodal ocular imaging and associated research studies to the modern-day clinical investigation of CSCR has been significant. This review aims to provide an overview of the most significant epidemiological and genetic studies of CSCR, in addition to describing its clinical and multimodal imaging features. The review also provides an update of the latest evidence from studies investigating pathophysiological mechanisms in CSCR and current opinions on multimodal imaging to better classify this complex retinal disease.

Guiding organs-on-chips towards applications: a balancing act between integration of advanced technologies and standardization

Organs-on-chips (OoC) are in vitro models that emulate key functionalities of tissues or organs in a miniaturized and highly controlled manner. Due to their high versatility, OoC have evolved as promising alternatives to animal testing for a more effective drug development pipeline. Additionally, OoC are revealing increased predictive power for toxicity screening applications as well as (patho-) physiology research models. It is anticipated that enabling technologies such as biofabrication, multimodality imaging, and artificial intelligence will play a critical role in the development of the next generation of OoC. These domains are expected to increase the mimicry of the human micro-physiology and functionality, enhance screening of cellular events, and generate high-content data for improved prediction. Although exponentially growing, the OoC field will strongly benefit from standardized tools to upgrade its implementational power. The complexity derived from the integration of multiple technologies and the current absence of concrete guidelines for establishing standards may be the reason for the slower adoption of OoC by industry, despite the fast progress of the field. Therefore, we argue that it is essential to consider standardization early on when using new enabling technologies, and we provide examples to illustrate how to maintain a focus on technology standards as these new technologies are used to build innovative OoC applications. Moreover, we stress the importance of informed design, use, and analysis decisions. Finally, we argue that this early focus on standards in innovation for OoC will facilitate their implementation.

Uncertainty estimation and evaluation of deformation image registration based convolutional neural networks.

Objective&#xD;Fast and accurate deformable image registration (DIR) that include DIR uncertainty estimation are essential for safe and reliable clinical deployment. While recent deep learning models have shown promise in predicting DIR with its uncertainty, challenges persist in proper uncertainty evaluation and hyperparameter optimization for these methods. This work aims to develop and evaluate a model that can perform fast DIR and predict its uncertainty in seconds.&#xD;Approach&#xD;In this study, we introduce a novel probabilistic multi-resolution image registration model utilizing convolutional neural networks (CNNs) to estimate a multivariate normal distributed dense displacement field (DDF) in a multimodal image registration problem. To assess the quality of the DDF distribution predicted by the model, we propose a new metric based on the Kullback-Leibler divergence. The performance of our approach was evaluated against three other DIR algorithms (VoxelMorph, Monte Carlo Drop-Out, and Monte Carlo B-splines) capable of predicting uncertainty. The evaluation of the models included not only the quality of the deformation but also the reliability of the estimated uncertainty. Our application investigated registration of a treatment planning computed tomography (CT) to follow-up cone beam CT for daily adaptive radiotherapy.&#xD;Main results&#xD;The hyperparameter tuning of the models showed that there is a trade-off between the reliability of the estimated uncertainty and the accuracy of the deformation. In the optimal trade-off our model excelled in contour propagation and uncertainty estimation (p < 0.01) compared to existing uncertainty estimation models. We obtained an average dice similarity coefficient of 0.89 and a KL-divergence of 0.15.&#xD;Significance&#xD;By addressing challenges in DIR uncertainty estimation and evaluation, our work showed that both the DIR and its uncertainty can be reliably predicted paving the way for safe deployment in clinical environment.&#xD.

Imperfect refractive index matching in scanning laser optical tomography and a method for digital correction.

Scanning laser optical tomography (SLOT) is a volumetric multi-modal imaging technique that is comparable to optical projection tomography and computer tomography. Image quality is crucially dependent on matching the refractive indexes (RIs) of the sample and surrounding medium, but RI matching often requires some effort and is never perfect. Reducing the burden of RI matching between the immersion medium and sample in biomedical imaging is a challenging and interesting task. We aim at implementing a post processing strategy for correcting SLOT measurements that have errors caused by RI mismatch. To better understand the problems with poorly matched Ris, simulated SLOT measurements with imperfect RI matching of the sample and medium are performed and presented here. A method to correct distorted measurements was developed and is presented and evaluated. This method is then applied to a sample containing fluorescent polystyrene beads and a sample made of olydimethylsiloxane with embedded fluorescent nanoparticles. From the simulations, it is evident that measurements with an RI mismatch larger than 0.02 and no correction yield considerably worse results compared to perfectly matched measurements. RI mismatches larger than 0.05 make it almost impossible to resolve finer details and structures. By contrast, the simulations imply that a measurement with an RI mismatch of up to 0.1 can still yield reasonable results if the presented correction method is applied. The experiments validate the simulated results for an RI mismatch of about 0.09. The method significantly improves the SLOT image quality for samples with imperfectly matched Ris. Although the absolutely best imaging quality will be achieved with perfect RI matching, these results pave the way for imaging in SLOT with RI mismatches while maintaining high image quality.

Correlative geochemical imaging of Desmophyllum dianthus reveals biomineralisation strategy as a key coral vital effect

The chemical and isotopic composition of stony coral skeletons form an important archive of past climate. However, these reconstructions are largely based on empirical relationships often complicated by “vital effects” arising from uncertain physiological processes of the coral holobiont. The skeletons of deep-sea corals, such as Desmophyllum dianthus, are characterised by micron-scale or larger geochemical heterogeneity associated with: (1) centres of calcification (COCs) where nucleation of new skeleton begins, and (2) fibres that thicken the skeleton. These features are difficult to sample cleanly using traditional techniques, resulting in uncertainty surrounding both the causes of geochemical differences and their influence on environmental signals. Here we combine optical, and in-situ chemical and isotopic, imaging tools across a range of spatial resolutions (~ 100 nm to 10 s of μm) in a correlative multimodal imaging (CMI) approach to isolate the microstructural geochemistry of each component. This reveals COCs are characterised by higher organic content, Mg, Li and Sr and lower U, B and δ11B compared to fibres, reflecting the contrasting biomineralisation mechanisms employed to construct each feature. CMI is rarely applied in Environmental/Earth Sciences, but here we illustrate the power of this approach to unpick the “vital effects” in D. dianthus, and by extension, other scleractinian corals.

Multimodal imaging in autosomal dominant Wolfram syndrome and long-term follow-up of laminations of the outer plexiform layer.

Multimodal imaging in autosomal dominant Wolfram syndrome and long-term follow-up of laminations of the outer plexiform layer.

Retinal metastasis from systemic carcinoma: clinical, multimodal imaging, and pathological characteristics from a multicenter case series.

Retinal metastasis from systemic carcinoma: clinical, multimodal imaging, and pathological characteristics from a multicenter case series.

Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis

Diet-induced increase in body weight is a growing health concern worldwide. Often accompanied by a low-grade metabolic inflammation that changes systemic functions, diet-induced alterations may contribute to neurodegenerative disorder progression as well. This study aims to non-invasively investigate diet-induced metabolic and inflammatory effects in the brain of an APPPS1 mouse model of Alzheimer’s disease. [18F]FDG, [18F]FTHA, and [18F]GE-180 were used for in vivo PET imaging in wild-type and APPPS1 mice. Ex vivo flow cytometry and histology in brains complemented the in vivo findings. 1H- magnetic resonance spectroscopy in the liver, plasma metabolomics and flow cytometry of the white adipose tissue were used to confirm metaflammatory condition in the periphery. We found disrupted glucose and fatty acid metabolism after Western diet consumption, with only small regional changes in glial-dependent neuroinflammation in the brains of APPPS1 mice. Further ex vivo investigations revealed cytotoxic T cell involvement in the brains of Western diet-fed mice and a disrupted plasma metabolome. 1H-magentic resonance spectroscopy and immunological results revealed diet-dependent inflammatory-like misbalance in livers and fatty tissue. Our multimodal imaging study highlights the role of the brain-liver-fat axis and the adaptive immune system in the disruption of brain homeostasis in amyloid models of Alzheimer’s disease.

Multimodality Imaging for Acquired Supravalvular Aortic Stenosis.

Multimodality Imaging for Acquired Supravalvular Aortic Stenosis.