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Introduction 287 The radiation burden due to cardiovascular imaging in Europe 287 Radiation risk 287 State-of-the-art technologies and their impact on radiation dose 288 New gamma camera detectors and software dedicated to cardiac imaging 288 Positron emission tomography systems for cardiac imaging 288 Cardiac computed tomography 290 Changed protocols, which have impact on dosimetry and patients 290 Single photon emission computed tomography protocols and tracers 290 Positron emission tomography protocols and tracers 292 Computed tomography protocols 292 Fusion computed tomography/single photon emission computed tomography–computed tomography/positron emission tomography imaging 293 Appropriate clinical use of non-invasive cardiac imaging for reducing global radiation exposure 293 Impact on costs 294 Conclusions 294 Cardiovascular diseases (CVDs) are the leading cause of death in Europe (5 million deaths per year) at a cost of €196 billion in 2009.1 Imaging techniques such as computed tomography (CT), single photon emission computed tomography (SPECT), and positron emission tomography (PET) play an increasingly important role in the diagnosis of CVD. Regarding myocardial perfusion imaging, scan volume has grown rapidly worldwide over the past two decades to 15–20 million procedures annually and diffusion of technology and expertise has led to its continued adoption across the developing world.2 However, there are concerns regarding the radiation burden associated with these diagnostic modalities. During the past 10 years, numerous technologies and data acquisition protocols for low-dose imaging have become available. The implementation of these technologies is always a balance between the long-term risk associated with exposure to ionizing radiation and the short-term risk related to impaired diagnostic accuracy. Furthermore, an important aspect to keep the dose as low as possible is to choose the most appropriate test for an individual patient using the correct acquisition protocol. From a clinical point of view, this implies to select the diagnostic test that is most likely to influence and direct patient care to improve outcome. From a technical point of view, this implies knowledge on differences between protocols and applying the protocol that results in the highest image quality with the lowest radiation exposure.3 Dose reduction is a multidisciplinary effort. For this reason, this article provides a consensus of three professional associations in the field of cardiac imaging—the European Association of Cardiovascular Imaging (EACVI), the Cardiovascular Committee of European Association of Nuclear Medicine (EANM), and the European Society of Cardiovascular Radiology (ESCR)—focusing on the balance between radiation dose and diagnostic accuracy, in agreement with the European guidelines endorsed by the involved associations. When considering the clinical indication for diagnostic procedures that use radiation, it is important to balance the short- and mid-term risks of the diseases remaining undetected and untreated against the long-term risk associated with radiation exposure.4 While ionizing radiation applied in the context of novel imaging technologies enables anatomical, functional, and molecular characterization of the whole heart with high accuracy, it poses a potential health risk because it may damage living tissues by changing cell structure and altering DNA. Sievert (Sv) is the unit of effective radiation dose in the International System of Units. One milliSv (mSv) corresponds to 10 J of energy of radiation transferred to 1 g of living tissue. The potential damage depends on not only the amount of absorbed energy and the different types of radiation but also the susceptibility of the tissue exposed to radiation. It has been shown that high-dose radiation exposure causes adverse health effects including an increased risk of cancer induction. Much of our knowledge about the risks from high-dose radiation is based on studies of survivors of the atomic bombs at Hiroshima and Nagasaki, as well as on the experiments with fruit flies performed by Hermann Muller, which built the basis for the linear non-threshold (LNT) model.5 The LNT model states that any radiation dose—no matter how small—may cause cancer. The LNT model currently still serves as the basis for international recommendations for radiation protection. This seems reasonable, despite some uncertainties about the accurate estimation of radiation-induced cancer risk. These uncertainties arise from the fact that the calculations are mainly based on data extrapolated from very high-dose exposure and only consider radiation dose while completely neglecting dose rate.6 Following the as low as reasonably achievable (ALARA) principle, contemporary cardiovascular examinations need to be performed with a radiation dose as low as possible. Recent literature indicates a median radiation exposure of 2–8 mSv for a nuclear myocardial perfusion scintigraphy (MPS),2 2–5 mSv for a cardiac PET,7 and 0.5–7 mSv for a coronary CT angiography (CCTA) scan.8 Moreover, in the setting of exclusion of clinically relevant coronary artery disease, the latest technologies in nuclear perfusion imaging and CT angiography enable examinations of <1 mSv.9 , 10 Estimation of risk from low-dose radiation exposure remains exceptionally difficult, but the risks are most likely small. Prospective trials focusing on adverse events associated with radiation exposure related to diagnostic procedures are difficult to perform. Randomized prospective data will probably hardly ever be available. A very recent study by Leuraud et al. 11 followed over 300 000 radiation-monitored workers up for a total of 8.22 million person-years hinted a potential positive association between protracted low-dose radiation exposure and leukaemia, thus lending support to the concept of a linear dose response at low doses. The results from the ongoing studies, such as the Epi-CT study,12 which is currently recruiting over one million children or young adults who had CT scans in nine European countries with the aim of evaluating the radiation-related risk of cancer, may provide more solid evidence. In the last 15 years, a fast technological evolution of scanners, hardware as well as software for image acquisition and reconstruction, has allowed a dramatic improvement of efficiency and quality of cardiac imaging resulting in progressive reduction of radiation doses to the patient2 , 7 , 8 which are becoming comparable to natural radiation exposure.13 This fast technological evolution may cause an imbalance between the natural life cycle of technological equipment and the need for updating to the state-of-the-art technology. We will summarize in the subsequent paragraphs the major evolutions in nuclear cardiology and cardiac CT technology, which have an impact on radiation dose reduction (Figures 1 and 2). Bar graph illustrating the average effective radiation doses of cardiac CT applying the various radiation dose reducing algorithms. Adapted from reference.14 Recommended radiotracer doses for MPI conventional scanners (white bar) and for scanners with new softwares and/or hardwares (grey bar). Full-dose PET radiotracer is used for 2D imaging and half-dose for 3D imaging; typically, equal dose of radiotracer is administered for rest and for stress PET MPI. Estimated dose is effective dose multiplied by administered activity. Dose is calculated for rest and stress scans separately, considering a single day examination. Adapted from reference.15 A growing number of nuclear medicine departments in Europe are now using a new generation of gamma cameras for cardiac imaging. In these so-called ‘CZT cameras’, the conventional sodium/iodine (Na/I) crystal used for the detection of gamma rays has been replaced by a cadmium–zinc–telluride (CZT) crystal. This crystal transforms directly the signal induced by gamma rays into electric impulses without the need for photodetectors. Manufacturers have taken advantage of these much thinner and more flexible CZT detectors to design the gamma cameras dedicated to cardiac imaging offering a larger surface for signal detection while focused on the heart region.16 , 17 The CZT gamma cameras provide a four- to seven-fold higher system sensitivity compared with Na/I-based cameras.18 This increase in signal detection efficiency has translated into a significant decrease in the dose of radiotracer required for cardiac scintigraphy. In turn, this has resulted to lower radiation exposure of patients and partly in shorter duration of acquisitions with preserved or even improved image quality and increase in the detection of coronary artery disease19 (Figure 3). A 60-year-old gentleman with typical angina. A single-day stress–rest low-dose protocol with 99mTc-tetrofosmin was performed, injecting 130 MBq at peak of exercise stress test and 390 MBq at rest. Stress and rest images were acquired for 6 and 5 min, respectively. CZT images reveal the presence of a reversible perfusion defect involving the inferoseptal wall, the inferior wall, the distal portion of the anteroseptal wall, and the apex. Ultralow-dose coronary CTA performed in a 67-year-old female (BMI 20) with a 320-row multidetector CT scanner, using a single heartbeat acquisition technique. By combining an 80-kVp tube voltage with third-generation iterative reconstructions, a sub-mSv radiation dose was obtained (0.7 mSv) with a high diagnostic quality of the examination. Volume rendering (A) and curved planar reconstruction (B) images show the presence of a high-risk, eccentric, soft tissue lesion in the proximal right coronary artery causing a high-grade stenosis. Another significant evolution has been provided by new reconstruction algorithms. Novel iterative reconstruction methods with resolution recovery and noise reduction provide higher image contrast (with sharper defects and borders) and significantly improve image quality, particularly for low-count imaging studies from half- and quarter-dose radiotracer protocols.20 The value of the novel software is that existing scanners can be upgraded with advanced software to reduce radiation dose, a much smaller capital investment than buying a new scanner. Thanks to the development of more efficient crystals and electronics, cardiac PET imaging has shifted from a 2D detection mode to a 3D detection mode. Acquisition of PET images in a 3D mode increases the efficiency of signal detection by a factor of 2 and therefore requires, for similar image quality, the injection of only half of the dose of radiotracer formerly required in 2D mode.21 , 22 PET images require correction for tissue attenuation, which is currently provided by using maps derived from low-dose CT acquisitions. This low-dose CT-related radiation exposure adds up to that from PET. Thus, PET–CT examination will most likely benefit from current progresses in CT image reconstruction to reach lower levels of radiation exposure. This is even more important in hybrid cardiac PET/CT imaging that is used to combine PET and coronary CT angiography information on myocardial function and coronary anatomy, which will benefit even more from CT dose-saving protocols.23 The emerging digital PET detector technology based on silicon photomultipliers will allow for a further substantial reduction of injected dose and therefore decrease radiation exposure. Recently, a new generation of scanners has entered the clinical arena, integrating a magnetic resonance (MR) with a PET device into a hybrid PET/MR scanner.24 , 25 The preliminary results show that attenuation maps can be obtained from MR, avoiding the need for CT attenuation maps, therefore reducing the ionizing radiation to the patient.26 State-of-the-art cardiac CT scanners are equipped with 64 or more detector rows. Several technological advances can and should be used to cardiac CT data at low radiation doses. fast with high resolution has been as it image In it has been the of prospective which has the for low radiation dose in this has regarding the cardiac in which images are compared with or acquisition protocols with it results in lower acquisition protocols can further reduce the these lower dose acquisition protocols require of the heart , The fact that higher tube at the can also be used to reduce patient radiation low tube as or reduce dose compared with the use of or high tube for increased image tube can further reduce dose by effective and of the types of tube current to the tube on the and amount of tissue to be can further reduce iterative reconstruction which improve image quality compared with the allow for cardiac imaging at lower radiation exposure (Figure A of the used for characterization of CT radiation dose is in of the used for characterization of CT radiation dose of the used for characterization of CT radiation dose Appropriate of radiotracer and acquisition protocols is in reducing patient radiation these be while in that diagnostic of the imaging test should be 2). a clinical the radiation dose to the patient resulting from the imaging should be in the clinical as by current international to reduce radiation exposure new imaging technologies for radiation exposure the test for the individual patient and by clinical guidelines and for performed cardiac to the clinical is not or the test is not the most appropriate with the a multidisciplinary a imaging protocol to and of examinations as a for patients dose of and total radiation exposure to imaging and in radiation exposure at and with new imaging technologies for radiation exposure the test for the individual patient and by clinical guidelines and for performed cardiac to the clinical is not or the test is not the most appropriate with the a multidisciplinary a imaging protocol to and of examinations as a for patients dose of and total radiation exposure to imaging and in radiation exposure at and with to reduce radiation exposure new imaging technologies for radiation exposure the test for the individual patient and by clinical guidelines and for performed cardiac to the clinical is not or the test is not the most appropriate with the a multidisciplinary a imaging protocol to and of examinations as a for patients dose of and total radiation exposure to imaging and in radiation exposure at and with new imaging technologies for radiation exposure the test for the individual patient and by clinical guidelines and for performed cardiac to the clinical is not or the test is not the most appropriate with the a multidisciplinary a imaging protocol to and of examinations as a for patients dose of and total radiation exposure to imaging and in radiation exposure at and with it is not possible to recommendations regarding the doses of for myocardial perfusion imaging due to the of a of the test to injected doses. 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Castleman disease (CD) is a group of rare and heterogeneous lymphoproliferative disorders. Accurate diagnosis and subtyping remain challenging. This report describes a rare case of idiopathic multicentric Castleman disease, not otherwise specified (iMCD-NOS), highlighting the causes of misdiagnosis, diagnostic strategy, and critical features of clinical subtyping. A 53-year-old male presented with a 4-month history of persistent right submandibular lymphadenopathy. During this period, he experienced two febrile episodes (max temp 39.0&#x202f;&#xb0;C), each lasting 2&#x202f;days, without associated respiratory symptoms. The fever resolved following intravenous antibiotic therapy at a local hospital, however, the lymphadenopathy did not improve and progressively enlarged. Core needle biopsy of the right submandibular lymph node at another municipal hospital revealed acute and chronic inflammation with fibrosis. He also reported occasional low-grade fever and night sweats, prompting admission to our hospital for further evaluation. On admission, physical examination revealed the largest lymph node measuring approximately 2.5&#x202f;&#xd7;&#x202f;2.0&#x202f;cm and purplish-red papules on the bilateral lower extremities. Laboratory findings revealed leukocytosis, eosinophilia, platelet (PLT) count: 296&#x202f;&#xd7;&#x202f;109/L (Normal), elevated C-reactive protein (66.31&#x202f;mg/L), and increased interleukin-6 (13.78&#x202f;pg./mL). PET-CT demonstrated metabolically active lymphadenopathy involving the bilateral cervical, submandibular, supraclavicular, retroperitoneal, and pelvic regions, suggestive of a neoplastic process. Under general anesthesia, an excisional biopsy of a right cervical lymph node was performed. Histopathological examination revealed disrupted lymph node architecture, with the presence of both atrophic and hyperplastic follicles. A subset of follicles showed an "onion-skin" appearance, accompanied by hyaline degeneration of small vessel walls in the paracortical region. The borders between the paracortex and lymphatic sinuses were indistinct, and proliferation of lymphocytes and plasma cells was observed in the sinus areas. Immunohistochemistry demonstrated CD38 positivity in the cortex and medullary sinuses, CD138 positivity in the cortex and paracortex, as well as positive staining for IgG4 and IgG. The pathological diagnosis was mixed-type Castleman disease. In the light of the patient's multicentric lymph node involvement, systemic inflammatory symptoms, elevated inflammatory markers, and the exclusion of HHV-8 infection as well as features suggestive of TAFRO or IPL, a final diagnosis of iMCD-NOS was made. Given the rarity of the disease and the limited experience with its management in our department, the patient was referred to the Department of Hematology at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. Following treatment with siltuximab plus prednisone, the patient's symptoms improved markedly, with resolution of fever and no recurrence of submandibular or cervical lymphadenopathy. This case illustrates the diagnostic challenges of idiopathic multicentric Castleman disease-not otherwise specified (iMCD-NOS) and underscores the importance of excisional biopsy over core needle biopsy, systematic exclusion of differential diagnoses, and multidisciplinary collaboration. The patient's journey through three hospitals before diagnosis offers three key lessons for clinicians: (1) The possibility of Castleman disease should be considered when a triad of unexplained lymphadenopathy, systemic symptoms, and elevated inflammatory markers is present. (2) When multicentric lymphadenopathy coexists with systemic inflammation, excisional biopsy-rather than core needle biopsy-is essential for an accurate diagnosis. (3) Systematic exclusion of HHV-8 infection, TAFRO/IPL features, and other mimickers is mandatory for proper iMCD-NOS subtyping. Enhanced awareness of this disease, as provided by this report, may facilitate early recognition and reduce diagnostic delays.

Death by neurologic criteria, previously called brain death, is a medicolegal concept, fraught with legal, ethical, and emotional considerations. The diagnosis is established clinically as described in the appropriate interdisciplinary guidelines. When adequate clinical evaluation cannot be performed, imaging including radionuclide brain perfusion scintigraphy (RBPS), four-vessel catheter angiography, or transcranial Doppler can be used as ancillary tests. Of these, RBPS is the more commonly performed test, used to establish the presence or absence of intracranial perfusion. Scintigraphic imaging for the presence or absence of intracranial perfusion is infrequently requested, which limits familiarity with both performing and interpreting these studies. The purpose of this article is to help the radiologist and nuclear medicine physician better understand the concept of death by neurologic criteria and the role of scintigraphic imaging in supporting the clinical diagnosis in the light of most recent multidisciplinary guidelines. A second goal is to describe how to interpret and report the relevant imaging studies, emphasizing differences between children and adults where applicable.

Graphene oxide, a 2D nanomaterial, has attracted significant attention for biomedical applications due to its exceptional properties, including tunable surface chemistry, excellent dispersibility, and abundant oxygen-containing functional groups that facilitate facile modification. Recent advancements in the synthesis and functionalization of graphene oxide-based materials have addressed their limitations, such as poor solubility and cytotoxicity, thereby making them safer and more effective for biomedical applications. This paper thoroughly outlines the structural attributes and principal qualities of graphene oxide-based materials, highlighting their mechanical strength, thermal stability, impermeability, electrical conductivity, and biological properties. Emerging developments in graphene oxide-based nanocomposites for fluorescence imaging, magnetic resonance imaging, photoacoustic imaging, Raman spectroscopy imaging, and multifunctional therapeutic platforms are thoroughly examined. Their effectiveness in biomedical scaffolds, wound-healing systems, controlled drug-release platforms, and antimicrobial coatings has been highlighted. Notwithstanding considerable advancements, issues related to cytotoxicity, biodegradability, long-term biosafety, and scalable production continue to impede broad clinical translation. This study offers a cutting-edge overview of graphene oxide-based biomedical systems and outlines promising pathways for advancing safer, more effective, and clinically relevant graphene-based healthcare technologies.

Computational modelling can deepen understanding of topics such as radiotracer pharmacokinetics, internal dosimetry, and decay-chain processes. However, modelling is often regarded as the exclusive domain of medical physicists and is not routinely included in the training of other medical professionals, including those in the radiation sciences such as radiographers, physicians, radiation therapists and nuclear medicine technologists. Using the intuitive bathtub analogy of system dynamics, we facilitate the inclusion of computational modelling in the training of healthcare professionals. Drawing on the example of a 99Mo/99mTc radionuclide generator used in nuclear medicine "hot labs", we illustrate how complex dynamics can be described and modelled through the highly visual, intuitive framework of system dynamics. We then examine the performance of first-year students, on modelling a 99Mo/99mTc generator in an examination question. Parent and daughter activity-time curves generated with system dynamics agree closely with the predictions of the Bateman equations. Student performance in modelling transient equilibrium under examination conditions using system dynamics (bathtub dynamics), demonstrates the accessibility of this approach. The highly visual and intuitive system dynamics approach facilitates modelling of complex processes including multi-compartment dynamics, tracer kinetics, internal dosimetry, and radionuclide generators. This is particularly relevant for students who lack the requisite quantitative training to engage with differential equations. System dynamics is a promising tool for democratising access to computational modelling among trainees and professionals in the radiation sciences. Computer models can help people understand how radioactive medicines behave in the body. This study explored a simple teaching approach that uses the familiar example of a bathtub filling and emptying to help students learn modelling concepts, and tested it using an example from nuclear medicine education. This study found that students were able to use this approach to model complex radioactive decay processes, with results that closely matched established scientific methods. This matters because it could help a wider range of healthcare students and professionals learn important modelling skills without needing advanced mathematics.

Lifelong premature ejaculation (LPE) is a prevalent male sexual dysfunction with unclear neurobiological mechanisms. Despite its high prevalence, the etiology of LPE remains debated, often attributed to psychological or biological factors. Recent neuroimaging studies have highlighted the role of central nervous system dysregulation in sexual behavior. This study investigates abnormal brain functions and altered network connectivity in LPE patients after visual sexual stimuli (VSS) using functional magnetic resonance imaging. Twenty-five LPE patients and 31 healthy controls (HCs) underwent resting-state and task-state functional magnetic resonance imaging (fMRI). Clinical data, including sexual history, self-reported intravaginal ejaculatory latency time, International Index of Erectile Function-5, the Chinese Index of Premature Ejaculation, anxiety/depression scores, and serum testosterone levels, were collected. Neuroimaging preprocessing and analysis focused on amplitude of low-frequency fluctuation, fractional ALFF, and regional homogeneity. Task-state fMRI compared brain activation patterns after VSS. Statistical analyses included voxel-based comparisons and network connectivity assessments using SPM12 and DPABI v3.0. LPE patients demonstrate distinct neurofunctional abnormalities after VSS, particularly hyperactivation in the precuneus. &#x200c;Clinical Data&#x200c;: LPE patients exhibited significantly lower International Index of Erectile Function-5 scores and higher depression rates compared to HCs, with no differences in age, BMI, or testosterone levels. Brain Activation&#x200c;: During VSS, LPE patients showed relative signal decrease in the middle cingulate cortex and left precentral gyrus compared to HCs. Regional homogeneity analysis revealed hyperactivation in the precuneus and fusiform gyrus post-stimulus. Network Connectivity&#x200c;: Altered connectivity in premature ejaculation patients involved the fusiform gyrus (linked to posterior cingulate, hippocampus, parahippocampus, and supplementary motor areas) and the superior parietal lobule (connected to the angular gyrus). These findings suggest that aberrant central nervous system processing of sexual stimuli contributes to premature ejaculation pathophysiology, offering potential targets for neuromodulatory therapies. The study focuses on the different activation patterns of patients with LPE from the perspective of sexual arousal. The methodological aspects of research, such as the use of images or videos in sexual stimulation, remain controversial. The findings of our network analysis only demonstrated a limited number of altered functional connections, and no established network metrics were provided to substantiate the claim of extensive network disruption. These factors collectively represent important limitations of the present study. The hyperactivity in this brain region observed in patients could represent a unique response to VSS among those with LPE, ultimately leading to alterations in their ejaculatory behavior.&#x200c;&#x200c;&#x200c;.

Brown adipose tissue (BAT) activity has been suggested to play a role in cancer progression. Previous studies have shown that BAT activity is higher in patients with cancer, and that BAT volume is a predictor of tumour recurrence and mortality in patients with cancer, but the data on melanoma are limited. Here, we re-analysed 2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (FDG-PET-CT) images from 135 patients with cutaneous melanoma treated at Turku University Hospital between 2012 and 2021 to assess associations among BAT, melanoma progression, patient survival, and patient weight. We applied a three-stage universal BAT threshold definition using predetermined standardised uptake value thresholds of 0.8, 1.0, and 1.2 g/ml, given the retrospective nature of our study. Of the 135 patients (81 men and 54 women; median age 61 years, interquartile range 54-71), 40 (29.6%), 24 (17.8%), and 19 (14.1%) were BAT-positive at the 0.8, 1.0, and 1.2 g/ml thresholds, respectively. Our results showed that patients with active melanoma on FDG-PET-CT imaging were more frequently BAT-positive at the 0.8 threshold (P = 0.026) and 1.0 threshold (P = 0.016). We also found a significantly higher BAT volume among patients who survived the observation period (0.8, 1.0, and 1.2 g/ml thresholds; P = 0.018, P = 0.038, and P = 0.571, respectively) and those who did not relapse (0.8, 1.0, and 1.2 g/ml thresholds; P = 0.631, P = 0.012, and P = 0.030, respectively). No association between BAT positivity and relapse-free survival or overall survival was observed at any threshold. Although higher BAT volumes were observed in subgroups of patients who survived or did not relapse, these findings were not supported by survival analyses and should be considered exploratory.

Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal neoplasm in which malignant B cells proliferate predominantly within small blood vessels. Because lymphadenopathy, mass lesions, circulating malignant cells, and specific radiological findings may be absent, IVLBCL can closely mimic other medical conditions, resulting in delayed diagnosis. This case is notable for a prolonged culture-negative sepsis-like presentation with persistent unexplained hypoxemia due to predominant pulmonary microvascular involvement, further obscured by lupus-like autoimmune features and subsequent COVID-19 infection. An older woman in her early 70s presented with fever, lethargy, weight loss, back pain, hypotension, raised inflammatory markers, cytopenia, markedly elevated lactate dehydrogenase (LDH), and progressive hypoxemia. She was initially treated for presumed sepsis, but repeated microbiological investigations and serial imaging did not identify an infectious source, and clinical improvement was not sustained. A transient malar rash and a positive antinuclear antibody raised concern for a lupus-like autoimmune disease; however, testing for anti-double-stranded DNA and extractable nuclear antigen was negative, and the broader autoimmune workup did not support systemic lupus erythematosus as the unifying diagnosis. Subsequent severe acute respiratory syndrome coronavirus 2 infection further complicated the interpretation of hypoxemia and deterioration. Despite antimicrobial therapy, corticosteroids, antiviral treatment, and supportive care, she developed progressive multiorgan failure and died approximately six weeks after admission. Postmortem examination revealed widespread multiorgan IVLBCL involving the lungs, heart, kidneys, liver, spleen, and multiple additional extranodal sites. Pulmonary capillary involvement provided a clinicopathological explanation for persistent unexplained hypoxemia. This case demonstrates how IVLBCL may remain concealed when several plausible diagnoses coexist. Persistent culture-negative fever, constitutional decline, cytopenia, high LDH, nondiagnostic imaging, treatment nonresponse, and unexplained hypoxemia should prompt consideration of IVLBCL and early tissue-based investigation.

Postoperative disease assessment in neuroblastoma remains challenging. We aimed to develop and validate a postoperative semiquantitative dual-tracer PET scoring system integrating [18F]FDOPA and [18F]FDG PET for outcome stratification in pediatric neuroblastoma. In this retrospective single-center study, 46 patients with histologically confirmed neuroblastoma who underwent curative-intent surgery, followed by postoperative dual-tracer PET/CT between 2014 and 2023, were included. Both PET studies were interpreted using a 3-point visual scoring system based on lesion uptake intensity (1: no abnormal uptake, 2: higher than background, and 3: intense uptake &#x2265;3&#xd7; liver SUVmean). Patients were stratified into dual PET-defined low, intermediate, and high-risk groups. Event-free survival (EFS) and overall survival (OS) were analyzed using Kaplan-Meier and multivariable Cox regression analyses. The discriminatory ability of the dual-tracer PET classification was quantified using Harrell C-index. Median patient age was 2.4 years, and 82.6% were classified as INRG high-risk. Median follow-up was 57.1 months. Patients were stratified into low risk (both scores = 1, n = 18), high risk (either score = 3, n = 9), and intermediate risk (remaining combinations, n = 19). The classification demonstrated significantly different 3-year EFS and OS rates: low-risk (94%, 100%), intermediate-risk (43%, 83%), and high-risk (11%, 42%). The dual PET model showed superior prognostic performance compared with single-tracer assessment (EFS C-index: 0.819 vs. 0.781 for FDG and 0.747 for FDOPA; OS C-index: 0.799 vs. 0.797 and 0.689, respectively). Dual PET classification remained an independent predictor after adjustment for age, MYCN amplification, and INRG classification. Postoperative dual-tracer PET provides robust prognostic stratification in pediatric neuroblastoma and may serve as a practical imaging biomarker for risk-adapted management.

Left ventricular (LV) hypertrabeculation, formerly termed LV noncompaction, is a heterogeneous myocardial entity linked to adverse cardiovascular outcomes. This study evaluated embolic risk in patients with dilated cardiomyopathy (DCM) according to the presence of hypertrabeculation and examined its prevalence and prognostic relevance across DCM genotypes. Clinical data from 1160 patients with DCM evaluated by cardiac magnetic resonance imaging and genetic testing (n=997 [86%]) were collected from 22 international centers. End points included embolic events, advanced heart failure events, and major ventricular arrhythmias. LV hypertrabeculation was identified in 354 patients (30.5%) by fractal analysis and in 343 (29.7%) according to Petersen criteria, with good concordance. After a median follow-up of 5.1 years (interquartile range, 2.8-7.4), embolic events occurred in 37 patients (3.2%), advanced heart failure in 62 (5.3%), and major ventricular arrhythmias in 136 (11.7%). Hypertrabeculation was not associated with increased embolic risk (hazard ratio, 1.5 [95% CI, 0.75-3.00]), even among patients in sinus rhythm with LV ejection fraction &#x2264;40% (hazard ratio, 1.89 [95% CI, 0.7-5.5]). In contrast, atrial fibrillation and reduced LV ejection fraction were associated with embolic events (both P<0.01). LV hypertrabeculation was not associated with an increased risk of major ventricular arrhythmias or advanced heart failure; genotype, LV ejection fraction, and late gadolinium enhancement emerged as the main predictors of adverse outcomes. The prevalence of LV hypertrabeculation varied across genotypes, with the highest prevalence observed in patients with sequence variants in motor sarcomeric genes (58%), TTN (38%), and genotype-negative status (33%), and the lowest prevalence observed among those with variants in cytoskeletal/Z-disk (7%) and nuclear envelope (5%) genes. Hypertrabeculation was not associated with adverse outcomes within any genotype. Although LV hypertrabeculation is common in DCM, it is not associated with worse outcomes and should not prompt differential clinical management. The embolic risk in patients with DCM and hypertrabeculation is low, including in those with reduced LV ejection fraction without atrial fibrillation, and does not support prophylactic anticoagulation in these patients.

This review delves into the advancements in Alzheimer's Disease (AD) research in China, focusing on insights, innovations, and future directions derived from the Chinese Preclinical Alzheimer's Disease Study (CPAS). With an aging population, AD prevalence has risen, increasing societal and economic burdens. CPAS, initiated in 2019, aims to identify early Alzheimer's pathology using plasma biomarkers and PET imaging. The study includes participants across the cognitive spectrum, including cognitively unimpaired individuals, patients with mild cognitive impairment (MCI), and patients with dementia, undergoing comprehensive assessments. Key findings include the impact of A&#x3b2;-PET on diagnosis and management, risk factors for amyloid pathology, and the expansion of biomarkers to include synaptic and other PET imaging markers. Future directions involve exploring disease-modifying therapies and applying multi-omics approaches to enhance the understanding and treatment of AD. These efforts are crucial for advancing personalized medicine and improving therapeutic outcomes in China and globally.

Enlarged perivascular spaces (EPVSs) in the basal ganglia (BG-EPVS) are an important marker of cerebral small vessel disease (cSVD), and EPVS in the centrum semiovale (CSO-EPVS) are part of the diagnostic criteria for cerebral amyloid angiopathy. We aimed to investigate associations of EPVS with reduced estimated glomerular filtration rate (eGFR) and glomerular hyperfiltration (higher than normal eGFR), which have scarcely been studied previously. In this cross-sectional study, we used pooled individual patient data from the Microbleeds International Collaborative Network which includes patients with ischemic stroke or transient ischemic attack. We investigated associations of impaired kidney function, defined as an eGFR of 30-60 or <30 mL/minute/1.73 m2, and glomerular hyperfiltration, defined as eGFR above the age-adjusted and sex-adjusted 95th centile, with BG-EPVS and CSO-EPVS severity. EPVS were rated according to a validated 5-point ordinal scale, and combined cSVD burden was rated using a validated 5-point ordinal scale with 1 point assigned for the presence of each of the following: severe white matter hyperintensities, &#x2265;1 cerebral microbleed, &#x2265;1 lacune, and BG-EPVS &#x2265;11. Normal glomerular filtration was defined as eGFR &#x2265;60 without hyperfiltration. We used multivariable ordinal logistic regression models to estimate risk of increased EPVS and cSVD burden severity adjusted for age, sex, and comorbidities. Seven thousand two hundred fifty-four patients (mean age 71 &#xb1; 13 years, 43% female) were included in the analysis, 357 with glomerular hyperfiltration, 1,692 with eGFR 30-60, and 256 with eGFR <30. Compared with normal glomerular filtration, hyperfiltration was independently associated with BG-EPVS (adjusted odds ratio [aOR] 1.38, 95% CI 1.11-1.70, p < 0.001) and CSO-EPVS (aOR 1.34, 95% CI 1.08-1.64, p = 0.011). Associations of eGFR 30-60 and eGFR <30 with EPVS were not statistically significant. Compared with normal glomerular filtration, eGFR <30 (aOR 1.27, 95% CI 1.03-1.57) was independently associated with increased cSVD burden, but eGFR 30-60 (aOR 1.06, 95% CI 0.95-1.20) and hyperfiltration (aOR 1.15, 95% CI 0.98-1.34) were not. Glomerular hyperfiltration was independently associated with EPVS severity, in both the basal ganglia and centrum semiovale. eGFR <30 was independently associated with total cSVD burden. A key limitation was a lack of repeated eGFR measurements.

Retrospective Cohort Study. To develop and externally validate an explainable machine-learning framework for perioperative risk stratification of radiographic adjacent segment degeneration (ASDeg) after short-segment lumbar fusion. Radiographic ASDeg is frequently observed after lumbar fusion and may represent an early structural phenotype preceding symptomatic adjacent segment disease (ASDis) in some patients. However, existing risk assessment approaches are limited by heterogeneous risk factors, insufficient model interpretability, and limited external validation. Machine-learning methods may improve perioperative risk stratification by integrating clinical, radiographic, surgical, and functional variables. Clinical data were retrospectively collected from two hospitals. The internal cohort included 570 patients who underwent posterior short-segment lumbar fusion for lumbar degenerative disease, and an independent cohort of 150 patients from another institution was used for external validation. The internal cohort was randomly divided into training and internal test sets at a 7:3 ratio using stratified sampling according to ASDeg status. Feature selection was performed exclusively in the training set using least absolute shrinkage and selection operator regression (LASSO), random forest-recursive feature elimination (RE-RFE), and Boruta. Five algorithms were developed and compared: logistic regression, random forest (RF), extreme gradient boosting (XGBoost), Light Gradient Boosting Machine(LightGBM), and multilayer perceptron (MLP). Model performance was evaluated using discrimination, calibration, precision-recall (P-R) analysis, and decision-curve analysis(DCA). Shapley Additive Explanations (SHAP) were used for model interpretation. Radiographic ASDeg occurred in 212 of 570 patients in the internal cohort. Five perioperative variables were retained for model construction: preoperative intervertebral space height (ISH), postoperative pelvic incidence-lumbar lordosis (PI-LL) mismatch, frailty, Coflex implantation, and preoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-defined lower-extremity dysfunction. Among the candidate algorithms, the RF model showed the highest discriminative performance, with an AUROC of 0.782 in the internal test set and 0.749 in the external validation cohort. SHAP analysis identified preoperative ISH as the strongest contributor to model output. This externally validated RF-based model provides a structured and interpretable framework for postoperative radiographic ASDeg risk stratification after short-segment lumbar fusion. By integrating clinically accessible perioperative variables, the model may support individualized imaging follow-up and provide a preliminary basis for future studies using symptomatic adjacent segment disease or revision surgery as clinically oriented endpoints.

Accurately assessing tumor response to immunotherapy remains a significant clinical challenge due to the unique response patterns and limitations of conventional anatomical imaging. This review explores the evolving application of PET/CT in evaluating immunotherapy efficacy through the novel lens of tumor metabolic reprogramming and immune escape mechanisms. First, we examine how metabolic imbalances in the tumor microenvironment mediate immune escape by suppressing immune cell function. The review subsequently analyzes advances in molecular imaging, focusing on the development of novel radiopharmaceuticals that target specific immunometabolism pathways, enabling direct visualization of immune cell dynamics. Furthermore, we analyze advances in novel tracers targeting specific immunometabolism processes for direct immune cell visualization, along with the application of radiomics for early response prediction. Finally, we address current technical and clinical challenges, outlining future directions aimed at constructing an integrated tumor metabolic-immune map and developing robust, PET-based patient stratification strategies to guide personalized therapeutic regimens. In conclusion, PET/CT is emerging as an indispensable multi-dimensional tool, providing critical real-time insights into immunometabolism activity to optimize therapeutic decision-making and improve clinical outcomes in cancer immunotherapy. Integrating these metabolic-immune signatures with other biomarker data holds promise for refining response assessment strategy and advancing personalized oncology.

In patients with progressive multiple sclerosis (PMS), previous studies reported increased cerebrospinal fluid (CSF) concentrations of inflammatory biomarkers, but these correlated only weakly with structural damage. We aimed to identify inflammatory CSF biomarkers that associate with tissue damage in PMS. We performed four substudies: [1] A cross-sectional exploratory study of patients with primary (PPMS) or secondary progressive MS (SPMS) (n&#xa0;=&#xa0;38) in whom we explored correlations between CSF concentrations of 1128 proteins and CSF neurofilament light chain (NFL) and myelin basic protein. [2] A cross-sectional confirmatory study where a protein of main interest, chitinase-1 (CHIT1), was analyzed in 104 patients with PPMS (n&#xa0;=&#xa0;78) or SPMS (n&#xa0;=&#xa0;26) and compared with 38 symptomatic controls. [3] Associations between CSF concentrations of CHIT1 and other disease biomarkers including CSF- and magnetic resonance imaging (MRI)-based measures of white matter injury in patients with PPMS (n&#xa0;=&#xa0;59). [4] A longitudinal study of effects of treatment with methylprednisolone, natalizumab, dimethyl fumarate, or placebo on CHIT1 in CSF in patients with PMS. Substudy [1] identified three proteins that correlated with CSF NFL: soluble B-cell maturation antigen, CC chemokine ligand 22, and CHIT1. CHIT1 showed a strong correlation with CSF NFL (&#x3c1;&#xa0;=&#xa0;0.61, q&#xa0;=&#xa0;0.008) and was selected for further analyses. Substudy [2] showed that patients with progressive MS had higher CSF concentrations of CHIT1 than symptomatic controls (all p&#xa0;<&#xa0;0.001). In substudy [3], CSF concentrations of CHIT1 correlated with increased lesion volume (p&#xa0;<&#xa0;0.001) and decreased magnetization transfer ratio (p&#xa0;=&#xa0;0.001) of lesions, decreased fractional anisotropy (p&#xa0;<&#xa0;0.001) and increased mean diffusivity of normal-appearing white matter (p&#xa0;=&#xa0;0.044) and lesions (p&#xa0;=&#xa0;0.005) in patients with PPMS. Substudy [4] showed that natalizumab treatment reduced CSF CHIT1 concentrations (p&#xa0;=&#xa0;0.005) in PMS. CSF CHIT1 concentrations are associated with neuroaxonal and white matter injury in patients with PPMS and responsive to disease-modifying therapy in PMS.

18F-NaF PET/CT is widely used in prostate cancer for detecting skeletal metastases, but the examination also contains structural and metabolic information potentially relevant to bone health assessment. This study evaluated feasibility of this dual-parameter approach for opportunistic bone health assessment in prostate cancer. This was a retrospective cross-sectional. A total of 105 men with prostate cancer without bone metastasis underwent 18F-NaF PET/CT. Stand-alone diagnostic CT-L1 was available in 76 patients and was used as an external structural reference for feasibility analysis and gray-zone stratification. Patient-level analyses used mean lumbar SUVavg and mean PET/CT-derived trabecular attenuation across L1-L4. Vertebra-level analyses used all available same-level SUVavg and same-level PET/CT-derived trabecular attenuation measurements. Patient-level metabolic-structural discordance on 18F-NaF PET/CT was assessed. PET/CT-derived L1 trabecular attenuation agreed strongly with stand-alone diagnostic CT-L1, with a correlation coefficient of 0.929 and an intraclass correlation coefficient of 0.916. In the paired diagnostic CT, cross-validated discrimination for low diagnostic CT-L1 thresholds was already high with low-dose CT alone, and adding SUV did not improve performance. However, among 41 patients in the stand-alone diagnostic CT gray zone of 110-160 HU, 19 (46.3%) were classified as low 18F-NaF uptake. At the patient level, mean SUVavg across L1-L4 correlated positively with mean PET/CT-derived trabecular attenuation across L1-L4 (r = 0.521, p<0.001). In the vertebra-level mixed-effects model, each 10-HU increase in trabecular attenuation was associated with a 0.084-unit increase in SUVavg (95% CI: 0.058 to 0.110; p<0.001). Nine patients showed a higher-TA but low-uptake phenotype, whereas 30 showed low TA with higher uptake. In prostate cancer, 18F-NaF PET/CT may feasibly support opportunistic bone health assessment by integrating low-dose CT-derived trabecular attenuation and 18F-NaF uptake within the same examination. The clinical contribution of 18F-NaF uptake appears to lie more in refining gray-zone stratification and identifying metabolically discordant patients. These feasibility findings are hypothesis-generating and require prospective validation against DXA and fracture endpoints before clinical use.

Primary bone lymphoma (PBL) is a rare extranodal lymphoma accounting for approximately 7% of malignant primary bone tumors. It typically presents with nonspecific features, frequently resulting in diagnostic delay and inappropriate initial management. We retrospectively analyzed the characteristics of 72 patients diagnosed with PBL between 1966 and 2025 at a tertiary referral center in Spain. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype. The most frequent presentations included persistent bone pain, pathological fractures, and palpable masses, often associated with elevated LDH levels or underlying immunosuppressive conditions. Imaging findings were heterogeneous, ranging from permeative lytic patterns to sclerotic lesions, occasionally resembling osteomyelitis or other aggressive neoplasms. MRI proved essential for early detection, accurate assessment of bone marrow infiltration, and soft tissue extension, while CT played a key role in biopsy guidance. FDG PET/CT was critical for staging, restaging, and treatment response evaluation. Diagnostic precision depended heavily on close clinico-radiological-pathological correlation, particularly in cases with atypical or misleading imaging patterns. Most patients were treated with combined chemotherapy and radiotherapy, which was associated with high response rates and favorable survival outcomes. PBL is an uncommon but potentially curable malignancy. Early diagnosis requires a high index of suspicion and systematic integration of clinical data, laboratory findings, and multimodal imaging. PBL should be systematically considered in patients presenting with aggressive-appearing bone lesions, pathological fractures, or unexplained marrow replacement, especially in the presence of elevated LDH levels or immunosuppression, in order to prevent diagnostic delay and optimize outcomes.

The rapid advancement of digital pathology has opened unprecedented opportunities for intelligent diagnosis in renal cell tumor. However, there remains a significant gap in the availability of reliable deep learning models capable of comprehensive kidney cancer detection, classification, grading, and survival prediction. This study retrospectively analyzed 11,135 whole-slide images (WSIs) from 7033 patients with renal tumor, sourced from four medical centers and two public cohorts. Histopathological representations were extracted using the foundation model Prov-GigaPath. A full-stack renal tumor diagnosis and prognosis framework was developed by combining fully supervised learning and weakly supervised multi-instance learning to enable both regional characterization and patient-level inference. The deep learning model demonstrated high accuracy in identifying normal tissue (AUC&#x2009;=&#x2009;0.990), tumor tissue (AUC&#x2009;=&#x2009;0.982), necrosis tissue (AUC&#x2009;=&#x2009;0.994), sarcomatoid differentiation (AUC&#x2009;=&#x2009;0.967), and pseudocapsule tissue (AUC&#x2009;=&#x2009;0.990) across various pathological types of renal cell tumor. For nine major subtypes of renal cell tumor, classification AUC reached 0.956-0.998 across multi-center validation cohorts. WHO/ISUP nuclear grade prediction for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) achieved an AUC of 0.867. A whole-slide-derived pan-renal cell tumor pathological risk score independently predicted overall survival and significantly outperformed WHO/ISUP grading in prognostic stratification (p&#x2009;<&#x2009;0.001). We developed and validated a comprehensive AI framework integrating tissue-region detection, renal tumor subtype classification, nuclear grading, and survival prediction. These findings support its potential as a decision-support tool for renal tumor pathology, while prospective workflow-based studies are warranted to determine its clinical utility and impact on pathologist performance.

To assess the pathogenicity of a novel duplication in the RP17 locus identified in a cone dystrophy proband with biallelic CEP290 variants. Structural variants (SVs) in this locus have previously been associated with dominant retinitis pigmentosa. Inheritance of the duplication was assessed by breakpoint polymerase chain reaction (PCR). Ophthalmic evaluation included fundus examination, multimodal retinal imaging, and full-field electroretinogram (ERG). A proband-derived pluripotent stem cell line was differentiated into photoreceptor precursor cells (PPCs) and retinal organoids (ROs). Variant-induced mis-splicing of CEP290 was assessed by reverse-transcription PCR (RT-PCR) and long-read cDNA sequencing, and immunohistochemistry was used to assess photoreceptor morphology. Expression of GDPD1 was quantified by quantitative RT-PCR. The proband and father carried the 324-kb duplication in the RP17 locus. The father was clinically unaffected, but the proband showed features of cone dystrophy, including reduced visual acuity, foveal abnormalities, diminished cone density, and preserved dark-adapted but absent light-adapted ERG responses. The compound heterozygous variants in CEP290 resulted in pseudoexon inclusion and exon 36 skipping in patient-derived retinal cells. Immunohistochemistry revealed altered ciliation and reduced trafficking of L/M opsin and rhodopsin in ROs. In silico modeling predicted that the novel RP17 duplication does not disrupt chromatin looping, and GDPD1 expression was not upregulated in patient ROs, in contrast to pathogenic RP17-SVs. The cone dystrophy phenotype of the proband can be attributed to the CEP290 variants, whereas the novel RP17 duplication can be classified as likely benign based on the integrated evidence. These findings emphasize the importance of modeling and functional studies for accurately classifying RP17-SVs and preventing misinterpretation in clinical diagnostics.