Clinical physiology and functional imagingNiklas Vartiainen, Antti-Pekka E Rissanen, Suvi Hartikainen, Svantte Halttunen, Aleksi J Leikas, Elina Kariniemi, Eero Strengell, Paavo-Ilari Kuikka, Juha E K …
BACKGROUND: In patients with suspected coronary artery disease (CAD), diffusely impaired hyperaemic myocardial blood flow (MBF) may indicate a multivessel epicardial CAD but also impaired coronary microcirculation. We assessed whether relative hyperaemic MBF-that is, the ratio of the lowest to the highest regional hyperaemic MBF-predicts obstructive CAD in patients with diffusely impaired hyperaemic MBF. METHODS: We studied 874 patients who underwent coronary computed tomography angiography and [15O]H2O myocardial perfusion imaging with positron emission tomography at Kuopio University Hospital, Finland, in 2017-2023. The final analyses included 64 patients who had diffusely impaired hyperaemic MBF and were subsequently referred to invasive coronary angiography (ICA). RESULTS: In ICA, 34/64 (53%) patients had obstructive CAD. Compared to patients with non-obstructive CAD, those with obstructive CAD had lower relative hyperaemic MBF: 66% (95% CI 62-69%) versus 52% (95% CI 47-57%), respectively (p < 0.001). When relative hyperaemic MBF was used to predict the presence of obstructive CAD in ICA, the receiver operating characteristic analysis showed an area under the curve of 0.778 (95% CI 0.666-0.891). In binary logistic regression analysis, relative hyperaemic MBF independently predicted obstructive CAD (OR = 0.92 [95% CI 0.86-0.97], p = 0.004). CONCLUSION: Obstructive CAD is more likely in patients with lower relative hyperaemic MBF. Consequently, relative hyperaemic MBF may have clinical utility in patients with suspected CAD and diffusely impaired hyperaemic MBF.
Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology AssociationJesse Johnson, Lynn Griffin, Kathryn Vickery, Elissa Randall
Standardized uptake value maximum (SUVmax), metabolic tumor volumes (MTV), and total lesion glycolysis (TLG) are metabolic parameters used to quantify tumors detected on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). This is a subset project from a larger pilot study where dogs diagnosed with lymphoma via lymph node aspirates were staged and monitored with serial 18F-FDG PET/CT before, during, and after completion of standard of care chemotherapy. The aim of this prospective study was to evaluate metabolic parameters within the spleen in dogs with naive lymphoma and establish cutoff values for these metabolic parameters to predict lymphoma dissemination to the spleen (n = 7 dogs, 17 splenic samples). Splenic contours were performed at each time point to compare splenic cytology to splenic SUVmax, MTV, and TLG. Statistically significant receiver operating characteristic (ROC) curve-derived cutoff values were found for SUVmax (cutoff > 3.55, p ≤ 0.05) and MTV with a threshold of 1.5 SUV (cutoff > 325.7, p ≤ 0.05). Additionally, there are significantly higher mean/median splenic SUV, MTV, and TLG among dogs with lymphoma in the spleen compared to those with benign splenic cytology. Therefore, certain cutoff values for SUVmax, MTV, and TLG may be able to predict splenic dissemination. These results may allow for noninvasive staging, monitoring of therapeutic response, and evaluation for recurrence of lymphoma following remission.
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseasesChinese Thoracic Society, Chinese Medical Association, Chinese Association of Chest Physicians, National Collaborative Group for Prevention and Treatment of Pu…
Radionuclide pulmonary ventilation/perfusion (V/Q) imaging is an important non-invasive tool for diagnosing pulmonary thromboembolism (PTE) and is used for screening, follow-up, and assessment of treatment response of PTE and chronic thromboembolic pulmonary hypertension (CTEPH). Currently, hospitals in China differ in their use of planar and tomographic acquisition methods for V/Q imaging, and interpretation requires a high level of expertise among nuclear medicine physicians. After surveying the nuclear medicine departments of multiple hospitals and holding expert discussions, the working group developed the Expert consensus on the operational protocol for radionuclide pulmonary ventilation/perfusion scintigraphy of pulmonary thromboembolism. This consensus covers examination procedures, diagnostic approaches, and precautions, with the aim of standardizing the clinical application of V/Q imaging procedures and their clinical application in PTE diagnosis. The following recommendations were formulated.Summary of RecommendationsRecommendation 1: For ventilation imaging, 99mTc-Technegas is recommended as the preferred radiopharmaceutical. During the preparation of Technegas, the working group recommends wetting the crucible with anhydrous ethanol before the addition of the sodium pertechnetate solution to improve the efficiency and quality of Technegas generation. If Technegas is unavailable, 99mTc-Diethylenetriaminepentaacetic acid (99mTc-DTPA) aerosol may be used as an alternative (Consensus level: 100%).Recommendation 2: Routine supplemental oxygen is suggested before pulmonary perfusion imaging to prevent false-positive images caused by pulmonary vasospasm. The recommended oxygen flow rate is 2-4 L/min, with an inhalation duration of 5-10 minutes (Consensus level: 83.3%).Recommendation 3: For pulmonary perfusion imaging, 200 000-700 000 radiopharmaceutical particles (mean, approximately 400 000) should be administered, with the recommended activity of 120-240 MBq (3-6 mCi). For patients with severe pulmonary hypertension, conditions with right-to-left heart shunting, or a history of single-lung transplantation, the particle number should be reduced to 100 000-200 000 (Consensus level: 83.3%).Recommendation 4: Gently agitate and homogenize the suspension of 99mTc-macroaggregated human serum albumin (99mTc-MAA) prior to injection. With the patient supine and breathing at normal tidal volume, slowly inject the tracer over several respiratory cycles through a patent intravenous line, continuously monitoring for adverse reactions; discontinue immediately if discomfort occurs. Strictly avoid backflow of blood into the syringe, which may cause particulate aggregation and bolus formation, leading to artifactual hot spots (Consensus level: 100%).Recommendation 5: For patients with protein allergies, a routine skin test is recommended before pulmonary perfusion imaging. Inject 0.1 ml of 99mTc-MAA suspension into the appropriate part of the forearm and observe for 15-20 minutes. If there is no positive reaction, perfusion imaging can be proceeded, with close observation and emergency medications on standby. If the skin test is positive, pulmonary perfusion imaging is not recommended. Routine skin testing is not indicated in patients without a history of allergy (Consensus level: 83.3%).Recommendation 6: For the 2-day acquisition protocol, perform pulmonary perfusion imaging on the first day. If the result is abnormal, perform pulmonary ventilation imaging the following day to aid diagnosis; if the perfusion imaging result is normal, pulmonary ventilation imaging may be omitted (Consensus level: 83.3%).Recommendation 7: For pregnant women with suspected PTE, if V/Q imaging is considered necessary after clinical assessment, a 2-day protocol is recommended. Dose reduction is recommended for lung perfusion imaging, the recommended dose of 99mTc-MAA is 50 MBq (1.35 mCi) (Consensus level: 100%).Recommendation 8: When the 1-day acquisition protocol is used, perfusion imaging may be performed immediately after completion of ventilation imaging. To ensure the clarity and accuracy of pulmonary perfusion imaging, the perfusion count rate should be 3-4 times the ventilation count rate (Consensus level: 100%).Recommendation 9: Avoid ambiguous phrasing such as "possible pulmonary embolism" in image reports. Interpretations should provide a definitive conclusion, such as "pulmonary embolism present", "pulmonary embolism absent", or another specific conclusion, after excluding other causes of impaired pulmonary perfusion (e.g., Takayasu arteritis, mediastinitis or pulmonary arterial sarcoma). When the diagnosis remains uncertain, the report should state, "pulmonary embolism cannot be excluded; correlation with clinical findings and other imaging examinations is recommended" to support subsequent clinical assessment and therapeutic decision-making (Consensus level: 100%).Recommendation 10: For patients with CTEPH, visual semi-quantitative analysis (Begic/Meyer score) may serve as an adjunctive tool for efficacy assessment after percutaneous pulmonary balloon angioplasty (BPA) or pulmonary endarterectomy (PEA). Where institutional resources permit, structured reporting is encouraged to improve the clarity and reproducibility of segmental impairment documentation (Consensus level: 100%).
European radiology experimentalHaifeng Gu, Yue Jiang, Jun Cai, Gang Yang, Jianrui Li, Sui Chen, Song Luo, Longjiang Zhang
OBJECTIVE: This study aimed to define the minimum positron emission tomography (PET) acquisition time for chest PET/magnetic resonance imaging (MRI), providing image quality and lesion detectability comparable to a 20-min reference. MATERIALS AND METHODS: In this retrospective study, list-mode data from 101 patients undergoing chest 18F-fluorodeoxyglucose (18F-FDG) PET/MRI on a 3-T PET/MRI system were reconstructed to simulate 10 acquisition times (0.5-20 min). Two readers assessed subjective image quality using a 5-point Likert scale. Quantitative parameters, including maximum, mean of the lesion standardized uptake value (L_SUVmax, L_SUVmean), image noise ratio (INR), and lesion-to-background ratio (LBR), were measured. Lesion detectability was defined as the miss rate relative to lesions visible on the 20-min reference acquisition. RESULTS: In 101 patients, 283 lesions were identified. Subjective scores increased from a median of 2 (interquartile range 2-2) at 0.5 min to 5 (5-5) at 7 min (p < 0.001), then plateaued (7-20 min; all p = 1.000). L_SUVmax, L_SUVmean, and LBR inversely correlated with scan duration (all p < 0.001). L_SUVmean stabilized at 3 min (p = 1.000), while L_SUVmax/LBR stabilized at 5 min (p = 1.000). INR required 10 min (p ≥ 0.054). Lesion miss rates increased time dependently, from 0% at 15 min to 7.77% at 0.5 min. CONCLUSION: A 7-min acquisition time provided subjective quality and detectability comparable to the 20-min protocol, supporting routine use. For quantitative assessments, 3-5 min sufficed, and patients with shorter 18F-FDG uptake or larger lesions may be adequately assessed with 2 min. KEY POINTS: Question What is the minimum PET acquisition time for chest 18F-FDG PET/MRI that maintains image quality and lesion detectability equivalent to a 20‑min reference? Findings A 7‑min PET acquisition matches 20‑min image quality and detectability; quantitative parameters stabilize at 3‑5 min; 2 min suffices for patients with shorter uptake or larger lesions. Relevance statement Reducing PET acquisition time to 7 min enhances patient comfort, reduces motion artifacts, and increases scanner throughput without compromising chest PET/MRI diagnostic performance, thereby improving patient experience and workflow efficiency. Further clinical validation is needed.
KCND3 encodes the voltage-gated potassium channel Kv4.3, and pathogenic variants in KCND3 are associated with spinocerebellar ataxia type 19/22 (SCA19/22) and related neurological phenotypes. Here, we report a Japanese patient harboring a novel KCND3 missense variant, classified as a variant of uncertain significance, who presented with a clinical phenotype compatible with SCA19/22, including slowly progressive cerebellar ataxia beginning in childhood, accompanied by asymmetric parkinsonism. Dopamine transporter single-photon emission computed tomography demonstrated reduced striatal uptake. Parkinsonian symptoms exhibited a partial response to dopaminergic therapy; however, the improvement was primarily based on clinical observation, with limited objective evidence supporting treatment efficacy. To our knowledge, abnormal dopamine transporter imaging has not been previously reported in patients with SCA19/22-related phenotypes. Although it was difficult to determine whether the parkinsonism was attributable to the KCND3 variant or to coexisting Lewy body disease, we reviewed the literature on parkinsonism associated with SCA19/22 and discussed the potential contributions of both pathologies in the present case.
INTRODUCTION: Primary aldosteronism (PA) is the most common cause of secondary hypertension, and accurate differentiation between unilateral and bilateral disease is critical for selecting appropriate therapy. In patients undergoing adrenalectomy, histopathological classification based on the International Histopathology Consensus for Unilateral Primary Aldosteronism provides a definitive reference for unilateral disease. Although adrenal vein sampling (AVS) remains the diagnostic gold standard, it is invasive, technically demanding and often limited by variable success rates. CXCR4-targeted positron emission tomography (CXCR4-PET)/CT has emerged as a promising non-invasive imaging modality capable of identifying aldosterone-producing lesions, but robust prospective evidence comparing it directly with AVS is lacking. This study aims to evaluate the diagnostic accuracy of CXCR4-PET/CT and to determine whether PET imaging can support treatment decision-making. METHODS AND ANALYSIS: This prospective single-centre diagnostic test accuracy study will enrol adults with confirmed PA and blood pressure ≥140/90 mm Hg. All participants will undergo adrenal CT, CXCR4-PET/CT and AVS following standardised protocols. Diagnostic accuracy will be evaluated by receiver operating characteristic curve, using a hierarchical reference standard, with AVS as the primary clinical reference and postoperative histopathology (according to the International Histopathology Consensus for Unilateral Primary Aldosteronism). Eligible patients may receive superselective adrenal arterial embolisation (SAAE), adrenalectomy or medical therapy. Clinical and biochemical outcomes, including blood pressure, aldosterone-renin parameters and medication burden, will be assessed at 1, 3, 6 and 12 months. Safety will be monitored and graded using Common Terminology Criteria for Adverse Events (CTCAE) V.5.0 criteria. Multivariable analyses will explore predictors of unilateral disease and factors associated with PET-AVS discordance. ETHICS AND DISSEMINATION: By integrating functional imaging, AVS, and treatment outcomes within a unified prospective framework, this study may provide comprehensive evaluations of CXCR4-PET/CT in PA to date. Findings may clarify its diagnostic utility, reduce dependence on AVS, and support precision treatment strategies in PA management. TRIAL REGISTRATION NUMBER: ChiCTR2600118245.
Medical science monitor : international medical journal of experimental and clinical researchBo Gao, Jun Yuan, Jin Wang, Xueqing Lv, Yongren Wang
BACKGROUND In the "one-stop-shop" stroke computed tomography (CT) scanning protocol, CT perfusion (CTP) can be performed either before or after CT angiography (CTA). This study analyzed the effect of different scanning strategies in one-stop-shop stroke CT on CTA image quality and perfusion parameters, aiming to optimize the scanning sequence of CTP and CTA in the one-stop-shop stroke CT protocol. MATERIAL AND METHODS We retrospectively analyzed 115 patients with suspected acute ischemic stroke admitted to our hospital between March and June 2024 and implemented 2 scanning strategies: CTP before CTA (group A, n=51) and CTA before CTP (group B, n=64) using 64-row CT equipment. The differences in CT values of the basilar artery, middle cerebral artery, superior sagittal sinus, and straight sinus, as well as craniocerebral perfusion parameter values and subjective scores of the CTA image quality, were compared between the 2 groups. The difference between venous CT values and the expert consensus-recommended intracranial venous CT value of 150 Hounsfield units (HU) was also compared. RESULTS There were no significant differences in arterial CT values or perfusion parameter values between groups A and B (P>0.0125). However, there was a significant difference in superior sagittal sinus CT values between the groups (P<0.0125). Group A showed more venous contamination (P<0.025), and its superior sagittal sinus CT value was significantly higher than the expert consensus-recommended value of 150 HU (P<0.0125). CONCLUSIONS CTA before CTP had no significant effect on perfusion parameters and was associated with reduced venous contamination. This strategy may serve as a practical alternative in similar 64-slice CT one-stop-shop stroke protocols.
The Behavioral and brain sciencesHamish A Deery, Rui Zheng, Sharna D Jamadar
Haueis and Colaço argue that metabolism is a generative principle for cognitive modelling. We extend this by bridging the "scaling gap" through functional PET (fPET) and network neuroscience. By measuring glucodynamics and the metabolic network of the brain, we can model how glucose metabolism enables network efficiency, temporal flexibility, information transfer, and ultimately the cognitive capacity of the human brain.
PURPOSE: Treatment response in unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is highly variable due to marked intratumoral heterogeneity, while existing predictive biomarkers lack accuracy. We aimed to develop and validate a pretreatment 18F-FDG positron emission tomography (PET)-computed tomography (CT)-derived spatiotemporal heterogeneity model to predict treatment response and prognosis in unresectable LA-NSCLC, and to explore its biological underpinnings. MATERIALS AND METHODS: In a multicenter cohort of 434 patients with unresectable LA-NSCLC (training: n = 215; internal validation: n = 93; external validation: n = 126), treatment response was classified as responsive or nonresponsive based on initial assessment. Four distinct habitats (PEThigh-CThigh, PETlow-CTlow, PETlow-CThigh, and PEThigh-CTlow) were generated via the Otsu algorithm. Temporal heterogeneity was quantified using metabolic hotspot displacement (normalized distance from the hotspot to the tumor centroid and normalized distance from the hotspot to the tumor periphery) and integrated with spatial radiomics to build a multidimensional spatiotemporal model. Model performance was evaluated against conventional metrics, with interpretability enhanced via nomogram and SHapley Additive exPlanations analysis. Survival outcomes were assessed using Kaplan-Meier curves, and public transcriptomic data were analyzed to characterize underlying pathways. RESULTS: The spatiotemporal model accurately predicted treatment response with AUCs of 0.822 (training), 0.821 (internal validation), and 0.810 (external validation), significantly outperforming conventional whole-tumor PET-CT models. It maintained robust generalizability across treatment subgroups and effectively stratified patients by progression-free survival and overall survival (P < .01). PEThigh-CThigh habitat volume fraction correlated with treatment resistance, whereas PETlow-CTlow habitat correlated with better response. Exploratory pathway analysis highlighted key pathways involving drug metabolism, glycolytic reprogramming, and immune microenvironment remodeling. CONCLUSION: This study establishes a noninvasive spatiotemporal heterogeneity biomarker based on 18F-FDG PET-CT that reliably predicts treatment response and prognostic outcomes in unresectable LA-NSCLC. It offers valuable insights for personalized clinical decision making and supports precision oncology.
RATIONALE: Primary pulmonary lymphoma (PPL) is an extremely rare malignant lung tumor that is frequently misdiagnosed as pneumonia or lung cancer due to its atypical radiological and clinical presentation. The rationale of this report is to elucidate the diagnostic value of combining computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in evaluating a rare presentation of PPL. PATIENT CONCERNS: A 44-year-old male was admitted after an incidental lung lesion was discovered during routine screening. He was completely asymptomatic, lacking respiratory or systemic "B symptoms." DIAGNOSES: A baseline chest CT identified a 3.9 × 3.5 cm soft-tissue mass in the right hilar region that compressed the right upper lobe bronchus, leading to secondary post-obstructive consolidation that lacked the characteristic air bronchogram sign. The CT also revealed an incidental 2.6 × 2.6 cm anterior mediastinal nodule. Subsequent whole-body 18F-FDG PET/CT demonstrated intense tracer uptake in the right hilar mass with a maximum standardized uptake value of 7.1 and mild-to-moderate uptake in an adjacent regional lymph node (maximum standardized uptake value of 3.2). The scan showed completely absent uptake in the anterior mediastinal nodule and the post-obstructive consolidation, arguing against metabolically active malignancy in those areas. Histopathological and immunohistochemical analysis from a bronchoscopic transbronchial lung biopsy confirmed primary pulmonary mucosa-associated lymphoid tissue lymphoma. INTERVENTIONS: The patient underwent localized radiotherapy targeting the right hilar mass and the FDG-avid regional hilar/posterior mediastinal lymph node. A total dose of 66 Gy was delivered in 18 fractions over the course of 3 weeks. OUTCOMES: At the 2-month post-discharge follow-up, a repeat chest CT revealed a marked reduction in the size of both the hilar lesion and the regional lymph nodes. The patient remained completely asymptomatic, and his laboratory parameters normalized. LESSONS: Differentiating PPL from central lung cancer and coexisting benign mediastinal abnormalities presents a significant clinical challenge, particularly when atypical radiological features mimic aggressive carcinomas. Whole-body 18F-FDG PET/CT serves as an invaluable, noninvasive modality for metabolic characterization, accurate loco-regional staging, and preventing clinical overstaging by effectively differentiating metabolically active lymphoma from concurrent benign lesions.
MedicineDae Gon Ryu, Cheol Woong Choi, Seong Jang Kim, Su Jin Kim, Su Bum Park, Jin Ook Jang, Cheol Min Lee, Bong Soo Son
The utility of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for T1 esophageal cancer is unclear. This study analyzed the usefulness of FDG-PET for T1 esophageal squamous cell carcinoma (ESCC). Medical records of patients with T1 ESCC between December 2008 and July 2024 at Pusan National University Yangsan Hospital were retrospectively reviewed. The preoperative FDG-PET/CT findings and final pathological results of patients with T1 ESCC confirmed by surgery or endoscopic resection were compared. Among the 133 patients with T1 ESCC, 84 (63.2%) had mucosal cancer, 49 (36.8%) had submucosal cancer, and 9 (6.8%) had lymph node metastasis. The maximal standardized uptake value (SUVmax) of the PET/CT images was positively correlated with the invasion depth (r = 0.670; P < .001) and tumor length (r = 0.518; P < .001). PET confirmed FDG uptake in 8 cases of mucosal cancer and 35 cases of submucosal cancer (9.5% vs 71.4%; P < .001). The negative predictive value and positive predictive value of FDG-PET/CT for identifying mucosal cancer were 84% and 81%, respectively. Of the 8 mucosal cancers in which FDG uptake was observed during PET, 5 (62.5%) were whole or near-circumferential lesions. FDG uptake observed using PET/CT was positively correlated with the invasion depth and tumor length of T1 ESCC. FDG-PET/CT may provide complementary information for risk stratification in patients with T1 ESCC.
Journal of neuro-oncologyZeynep Özdemir, Wolfgang Roll, Walter Stummer, Stjepana Kovac, Michael Müther
PURPOSE: Diffuse lower-grade glioma (DLGG), i.e. WHO grade 2 and 3 tumors, frequently manifests with epileptic seizures, significantly affecting quality of life. While [18F]FET PET is routinely used to assess glioma metabolism, differences between patients with and without glioma-related epilepsy have not yet been assessed systematically. The objective of this study was to assess whether preoperative [18F]FET PET uptake is associated with epileptic seizures at initial presentation in patients with DLGG. METHODS: This retrospective study included 121 patients with DLGG with preoperative [18F]FET PET (2015-2025). [18F]FET uptake parameters were determined in patients with measurable disease according to PET RANO 1.0 criteria. Seizure status was assessed exclusively for seizures occurring before surgery. Statistical analyses included Fisher's exact test, Mann-Whitney U test, and multivariable logistic regression. RESULTS: Seventy-eight patients (64%) demonstrated measurable disease in [18F]FET, of whom 57 (73%) presented with epileptic seizures compared to 17 (40%) in the no-uptake group (p < 0.001). In the measurable disease group, those with seizures exhibited significantly higher median TBRmax (3.02; IQR 2.35-4.00) and TBRmean (2.2; IQR 1.8-2.5) values than those without seizures (TBRmax 2.4; IQR 2.00-3.16, TBRmean 1.9; IQR 1.7-2.2). The tumor location did not account for the observed association between [18F]FET uptake and seizures (p > 0.05). In multivariable analyses, [18F]FET uptake remained independently associated with preoperative seizures (adjusted OR 2.86, 95% CI 1.18-7.07; p = 0.020). CONCLUSION: These findings demonstrate an association between [18F]FET uptake and glioma-related epilepsy in DLGG. Further research on amino acid transporter expression and glutamatergic pathways may elucidate underlying mechanisms.
NeurologyDror Shir, Alicia Algeciras-Schimnich, Yoav D Piura, Joshua A Bornhorst, Daniel J Figdore, Anas Elgenidi, Christian Lachner, Neill R Graff-Radford, Gregory S D…
BACKGROUND AND OBJECTIVES: Plasma phosphorylated tau (p-tau) 217 is increasingly used for Alzheimer disease (AD) diagnosis and treatment decisions but may be discordant with established AD biomarkers. False-positive (FP) plasma results may lead to overtreatment and false-negative (FN) results to missed or delayed disease-modifying therapies. We evaluated factors associated with discordant results. METHODS: This retrospective study included participants enrolled in memory and aging studies at Mayo Clinic with "positive" (>0.324 pg/mL) or "negative" (<0.186 pg/mL) plasma p-tau217 results and confirmatory AD biomarkers. Plasma results were classified as true positive (TP), true negative (TN), FP, or FN, referencing amyloid-PET and CSF p-tau181/β-amyloid (Aβ) 42. Clinical and laboratory variables were compared using univariate analyses; multivariable logistic regression evaluated independent associations with discordance. RESULTS: Among 706 participants (median 70.0 [interquartile range 15.8] years; 54% male), 60 (8.5%) had discordant plasma p-tau217 results. FN results (5.6%) were more frequent than FP results (2.8%; p = 0.007). Discordance was associated with older age (odds ratio [OR] 1.61 per decade, 95% CI 1.23-2.14) and obstructive sleep apnea (OR 1.94, 95% CI 1.08-3.49). FN (vs TP) results were associated with milder clinical stage (global Clinical Dementia Rating [CDR] ≤0.5 vs CDR ≥1; p < 0.001), higher Mini-Mental State Examination scores (OR 1.20 per point, 95% CI 1.05-1.36), obstructive sleep apnea (OR 2.01, 95% CI 1.01-4.3), higher body mass index (OR 1.11/kg/m2, 95% CI 1.03-1.20), and higher estimated glomerular filtration rate (eGFR: OR 1.33/10 mL/min/1.73 m2, 95% CI 1.05-1.69). In age-adjusted models, body mass index (OR 1.14, 95% CI 1.03-1.25), eGFR (OR 1.63/10 mL/min/1.73 m2, 95% CI 1.22-2.16), and earlier clinical stage (CDR ≤0.5) were independently associated with FN results. FP (vs TN) results were associated with older age (OR 2.37, 95% CI 1.36-4.09), thyroid disease (OR 4.41, 95% CI 1.36-14.3), lower eGFR (OR 0.48/10 mL/min/1.73 m2, 95% CI 0.31-0.66), and advanced disease stage (CDR ≥1). In age-adjusted models, eGFR (OR 0.54/10 mL/min/1.73 m2, 95% CI 0.35-0.82) and advanced disease stage (CDR ≥ 1 vs CDR 0: OR 11.11, 95% CI 2.0-50.0; vs CDR 0.5: OR 4.55, 95% CI 1.12-16.67) were independently associated with FP results. DISCUSSION: Plasma p-tau217 results and established AD biomarkers were discordant in 8.5% of participants. Clinical stage and factors related to brain amyloid clearance, renal clearance, and volume of distribution were associated with discordant results. These insights may inform mechanisms of discordance and identify patients requiring confirmatory biomarker measures.
Human brain mappingNarges Azizi, Hoda Borooghani, Iman Kiani, Zeinab Gharaylou, Dina Seyedi, Kavous Firouznia, Shahriar Kolahi
Cerebral small vessel disease (SVD) is a leading cause of stroke, vascular cognitive impairment, and functional decline in older adults. Emerging experimental and translational data implicate glymphatic dysfunction in SVD pathogenesis and in vascular amyloid accumulation. The analysis along the perivascular space (ALPS) index, derived from diffusion tensor imaging (DTI), noninvasively estimates water diffusivity along perivascular pathways and has been proposed as an indirect imaging marker related to glymphatic function. In this study, we aim to determine whether the baseline DTI-ALPS index is associated with baseline SVD burden and subsequent longitudinal changes in SVD markers and amyloid-β deposition in cognitively normal aging. We analyzed 204 cognitively normal participants from the Harvard Aging Brain Study with baseline and follow-up visits separated by 3 years. Primary MRI SVD outcomes were intracranial-volume-normalized white matter hyperintensities (WMH/ICV), and visual SVD ratings (Fazekas, ARWMC, perivascular space, and BOMBS [microbleed scale]). Secondary outcomes included cortical amyloid PET burden (PIB_FS_DVR_FLR). We tested the effects of time, baseline ALPS (z-scored), and the time-ALPS interaction using Bayesian mixed-effects models with subject-specific random intercepts adjusted for baseline age, sex, and education; amyloid models were additionally adjusted for APOE4 status. Continuous outcomes were modeled with Gaussian mixed-effects models, binary outcomes with Bernoulli mixed-effects models, and ordinal outcomes with Bayesian cumulative mixed-effects models. In a sensitivity analysis, ALPS was recalculated after excluding voxels with λ2/λ3 > 1.8, and the models were repeated using the crossing-fiber-adjusted index. Posterior means and 95% HDIs were the primary summaries. Multiplicity was controlled using the Benjamini-Hochberg false discovery rate procedure, and the resulting FDR-adjusted two-sided posterior tail-area p-analogues are reported as pcorrected. Over the 3-year follow-up, SVD and amyloid-β burden increased: WMH/ICV (β = 0.096, 95% HDI [0.069, 0.121], pcorrected < 0.001), cortical amyloid-β (β = 0.130, 95% HDI [0.106, 0.152], pcorrected < 0.001), Fazekas (β = 0.320, 95% HDI [0.088, 0.541], pcorrected = 0.010), ARWMC (β = 0.404, 95% HDI [0.165, 0.649], pcorrected = 0.004), basal ganglia (β = 0.318, 95% HDI [0.079, 0.546], pcorrected = 0.010), and centrum semiovale (β = 0.244, 95% HDI [0.026, 0.450], pcorrected = 0.025). PVS scores also increased over time. Higher baseline ALPS was associated with lower Fazekas severity (β = -0.742, 95% HDI [-1.281, -0.201], pcorrected = 0.026) and with attenuated amyloid accumulation over time (β = -0.025, 95% HDI [-0.049, -0.001], pcorrected = 0.039). In a sensitivity analysis excluding voxels with a high likelihood of substantial fiber crossing, the ALPS-by-time interaction for amyloid burden remained significant (β = -0.028, 95% HDI [-0.052, -0.003], pcorrected = 0.022), whereas the baseline association with Fazekas severity was attenuated (β = -0.413, 95% HDI [-0.966, 0.181], pcorrected = 0.751). Higher baseline WMH/ICV was associated with poorer baseline global cognition (PACC5) (β = -0.092, 95% HDI [-0.177, -0.011], pcorrected = 0.036), processing speed (β = -0.116, 95% HDI [-0.223, -0.010], pcorrected = 0.036), and executive function (β = -0.144, 95% HDI [-0.251, -0.029], pcorrected = 0.035). Higher baseline amyloid burden was associated with steeper PACC5 decline (β = -0.065, 95% HDI [-0.096, -0.033], pcorrected < 0.001). In cognitively normal older adults, higher conventional baseline ALPS was associated with lower Fazekas severity, although attenuation after crossing-fiber adjustment indicates that this cross-sectional relationship was sensitive to the microstructural composition of the ALPS regions. In contrast, higher baseline ALPS was associated with slower short-term amyloid-β accumulation, and this longitudinal association remained significant after crossing-fiber adjustment. Greater baseline amyloid burden was associated with more rapid decline in global cognition, whereas higher baseline WMH volume was associated with poorer baseline global cognition, processing speed, and executive function. These findings support ALPS as a candidate noninvasive diffusion marker associated with longitudinal amyloid-related change, while emphasizing the need for further validation of its relationship with SVD burden and its biological specificity.
Neuroimaging is crucial in early and accurate assessment of diagnosis, prognosis, and therapy optimization in patients with declining cognitive abilities. Imaging modalities now available for clinical indications related to neurodegenerative processes include Computed Tomography (CT), MR imaging, and PET imaging with 6 positron-emitting radiotracers approved at this time by the US Food and Drug Administration. The central focus of this article is the role of FDG-PET in clinical and research applications of patients with cognitive problems, and how the derived information may be effectively integrated with information acquired from other neuroimaging modalities.
Alzheimer's & dementia : the journal of the Alzheimer's AssociationSusan Ashrafzadeh-Kian, Daniel J Figdore, Joshua A Bornhorst, Patrick M Vanderboom, Sarah Callison, Gregory S Day, Christian Lachner, Neill Graff-Radford, Dror…
INTRODUCTION: Plasma phosphorylated tau 217 (p‑tau217) immunoassays are increasingly being used to assess Alzheimer's disease (AD) pathology despite limited data affirming test reliability over time. METHODS: Clinical performance of the Fujirebio Lumipulse G p‑tau217 assay was assessed in 744 Mayo Clinic patients presenting for evaluation of cognitive impairment between July 2024 and December 2025. Cerebrospinal fluid p‑tau181/amyloid beta 42 or amyloid positron emission tomography, within 1 year of p-tau217 testing, were used as reference. Analytical robustness was evaluated by tracking result frequencies over time, conducting quality control checks, performing 10 lot‑to‑lot comparisons, and comparing two versions of reagents. RESULTS: Diagnostic accuracy for detection of AD pathology was 93% (95% confidence interval 91-95) with 23% intermediate results. Reduced estimated glomerular filtration rate was associated with increased intermediate results among amyloid-negative individuals. Result frequencies remained stable, average imprecision was 8%, and analytical bias between lots and version changes were ≤ 11%. DISCUSSION: The findings support plasma p-tau217 reliability in clinical practice for evaluation of cognitively impaired individuals.
Alzheimer's & dementia : the journal of the Alzheimer's AssociationMenglan Pang, Holly M Brothers, John O'Gorman, Jennifer Murphy, Yuval Zabar, Tyler Lasky, Changyu Shen, Ivana Rubino, David Knopman
INTRODUCTION: Anti-amyloid antibody clinical trials with a high proportion of participants reaching treatment-related amyloid clearance (TRAC) had positive clinical outcomes. We evaluated the aducanumab phase 3 program to determine whether TRAC during the double-blind period was likewise associated with clinical benefit. METHODS: We pooled ENGAGE and EMERGE (E/E) aducanumab-treated participants in the amyloid positron emission tomography substudy who continued into the long-term extension ≤ 134 weeks (continuously treated population) and/or returned to the EMBARK redosing study 0.7 to 2.5 years after termination of E/E (treatment gap population). Clinical outcomes were stratified by week 78 TRAC status. RESULTS: TRAC participants had less clinical decline at week 78, week 134, and EMBARK baseline than non-TRAC participants. Post-TRAC, clinical decline was heterogeneous; approximately two thirds of TRAC participants had annualized decline of < 1 point on Clinical Dementia Rating Sum of Boxes. DISCUSSION: In these exploratory analyses, week 78 TRAC status was associated with better clinical outcomes. CLINICAL TRIAL REGISTRATION: NCT02484547, NCT02477800, NCT04241068.
Despite isolated REM sleep behaviour disorder (iRBD) reliably identifying individuals at high risk of developing Parkinson's disease (PD) or dementia with Lewy bodies (DLB), with more than 90% converting, the neurobiological markers of the conversion phenotype are not fully understood. Most previous studies have found univariate imaging biomarkers of phenoconversion, and most of these lack specificity for PD and DLB. Using a well-characterised iRBD cohort (N=21), receiving multiple PET and MRI scans, we aimed to assess if the inter-modality relationship can specifically predict conversion to PD or DLB. The patients received [18F]-DOPA, [11C]-Donepezil and [11C](R)-PK11195 PET and structural MRI scans to derive grey matter (GM) volume along with dynamic susceptibility contrast MRI to extract measures of microcirculatory dysregulation. We used a multimodal adaptation of the scaled sub-profile model to identify patterns of multimodal covariance across the PET and MRI scans. We identified a multimodal network characterised by high neuroinflammation, cholinergic dysfunction, GM atrophy and microcirculatory dysfunction with the covariance pattern converging in the medial occipito-parietal cortex (OPC). The combined pathology from the OPC and striatal [18F]-DOPA uptake was able to specifically predict conversion into DLB (sub-distribution hazard ratio=38.68, 95% confidence interval: 7.545-198.3), and this survived correction for age and disease duration. These findings demonstrate the feasibility of integrating multiple modalities in risk assessment and suggest that posterior cortical pathology, along with striatal dopaminergic impairment, could hold predictive value for phenotype-specific conversion of iRBD patients, and that multiple pathological processes converge in this brain region.
Medical physicsBingjie Wang, Sheng Bi, Xiaoyin Xu, Hairong Zheng, Dong Liang, Greta S P Mok, Shaozhen Yan, Zhanli Hu
BACKGROUND: Accurate and early diagnosis of Alzheimer's disease (AD) remains a major clinical challenge. This study aims to explore the value of multimodal positron emission tomography (PET) and magnetic resonance imaging (MRI) radiomics to improve diagnostic accuracy. PURPOSE: To develop and evaluate hippocampus-based multimodal PET/MRI radiomics models for AD classification and exploratory five-class classification, and to compare early fusion (EF) with multi-criteria decision-making (MCDM)-based decision-level fusion. METHOD: A total of 758 patients who underwent both PET ([18F]FDG and Amyloid-β) and MRI (3DT1, T1WI, T2WI, T2-FLAIR) were retrospectively included as the primary dataset in this study. 945 radiomic features (RFs) per sequence were extracted from the bilateral hippocampus. Models were evaluated on the primary cohort using a five-fold stratified cross-validation at the subject level (80% training and 20% testing in each fold). Feature selection was performed independently for each sequence using the Least Absolute Shrinkage and Selection Operator (LASSO). For multimodal PET/MR models, features from all six sequences were concatenated, and feature selection was applied (EF). Six classifiers were used to construct classification models for two tasks, including (1) AD/non-AD classification, and (2) exploratory five-class classification among AD, FTD, VaD, MCI, and other dementia. In addition, an MCDM-based strategy was implemented to fuse multimodal RFs and multi-classifiers. Modality-matched external validation was performed in an independent cohort of 45 patients with 3DT1 and Aβ PET available. Decision curve analysis (DCA) was employed to assess the clinical usefulness of the models. SHapley Additive exPlanations (SHAP) was applied to explore the interpretability of the EF-based model. RESULTS: Among the 758 patients in the primary dataset, AD, FTD, VaD, and MCI were present in 481 (63.5%), 34 (4.5%), 15 (2.0%), 136 (17.9%) cases, with 92 (12.1%) classified as the other dementia subtypes. The MCDM-based models achieved the highest area under the receiver operating characteristic curves (AUCs) for both tasks on the primary dataset (Task 1: AUC = 0.848; Task 2: AUC = 0.797), significantly higher than EF-based models in Task 2 (AUC = 0.782, p < 0.001) and showing comparable performance in Task 1 (AUC = 0.839, p = 0.629). On the external dataset, EF and MCDM models achieved AUCs of 0.741 and 0.761, respectively, for Task 1. The MCDM model showed a higher AUC than EF. DCA suggested potential net-benefit advantages for the multimodal models across selected threshold ranges. SHAP analysis identified wavelet-transformed texture features as the key predictors. CONCLUSION: Hippocampus-based PET/MRI radiomics models showed promising performance for binary AD classification, with further improvement achieved by the MCDM strategy. The five-class findings should be regarded as exploratory. External validation provides preliminary support for the reduced 3DT1-Aβ PET model and does not establish the generalizability of the complete six-modality framework.
Alzheimer's & dementia : the journal of the Alzheimer's AssociationLukas Frontzkowski, Sebastian Roemer-Cassiano, Johannes Gnörich, Daniel Janowitz, Hannah Eyob, Katharina Probst, Dario Dhoqina, Anna Dewenter, Anna Steward, Ze…
BACKGROUND: Tau pathology in Alzheimer's disease (AD) propagates along the brain's connectome, yet the mechanisms by which tau drives neuronal dysfunction remain unclear. We hypothesized that dysfunction primarily emerges in regions close to tau-harboring epicenters. METHODS: One hundred thirty-one amyloid-positive individuals underwent dynamic [18F]PI-2620 tau positron emission tomography. Kinetic modeling yielded distribution volume ratios (DVRs) and perfusion (R1). Tau epicenters were defined as top 10% DVR regions. Connectivity-based distance to epicenters was derived from normative resting-state functional connectivity. RESULTS: At the individual level, hypoperfusion was more closely related to distance from tau epicenters than to local tau deposition, particularly in early AD, consistent with diaschisis-like disconnection. With advancing biological disease severity, local tau deposition increasingly converged with hypoperfusion. Critically, hypoperfusion mediated the relationship between tau accumulation and cognitive decline. DISCUSSION: Tau epicenters shape the brain-wide pattern of neuronal dysfunction, while local tau burden determines the degree of damage driving cognitive decline.
BACKGROUND: Apathy is a frequent nonmotor symptom of multiple system atrophy (MSA) that worsens quality of life. Although frontostriatal dysfunction has been implicated in apathy, its neural basis in MSA remains insufficiently characterized. OBJECTIVES: To identify the neural substrates of apathy associated with MSA-specific neurodegenerative processes. METHODS: This retrospective cross-sectional study included 76 patients with cognitively preserved clinically established/probable MSA who underwent clinical and neuropsychological assessments, including the Apathy Scale and a separate depression measure, magnetic resonance imaging, and cerebral blood flow single-photon emission computed tomography. Clinical variables, gray matter volume, and voxel-wise perfusion were compared between apathy and non-apathy groups. Multivariate logistic regression was used to analyze the independent association of the significant perfusion cluster with apathy, and seed-based covariance analysis was used to explore network alterations. RESULTS: Apathy was present in 55.3% of patients and did not differ between motor subtypes. Compared with the non-apathy group, the apathy group showed lower visuospatial scores and frequency of neurogenic orthostatic hypotension, similar depression scores and gray matter volume, and reduced perfusion in the medial prefrontal cortex on voxel-wise perfusion analysis. These findings remained independently associated with apathy after adjustment for clinical variables. Seed-based covariance analysis suggested reduced positive covariance between the medial prefrontal cortex and cerebellar regions, predominantly in the posterior lobe. CONCLUSIONS: Apathy was common in MSA even with relatively preserved global cognition and distinct from depression. In addition to medial frontostriatal dysfunction, exploratory findings suggested that mechanisms related to cerebellar cognitive affective syndrome may contribute to its pathophysiology.
The Lancet. NeurologyTammie L S Benzinger, Petrice M Cogswell, Arvin Arani, Aisling M Chaney, Kent Hutson, Matthew F Glasser, Jonathan Graff-Radford, Jon McConathy, Cyrus A Raji, C…
Disease-modifying therapies and biomarker-based diagnostic frameworks will fundamentally altered the clinical diagnosis and management of Alzheimer's disease. Diagnosis is increasingly anchored in the biological evidence of pathology rather than clinical presentation alone, with implications for treatment eligibility, prognosis, and monitoring. In clinical practice, patients with memory complaints can present with complex mixed pathologies that develop across the lifespan. Brain imaging, particularly MRI and PET, plays a crucial role in visualising these cumulative abnormalities. With Alzheimer's disease-specific therapies now available in many regions of the world, amyloid PET plays a central role in establishing Alzheimer's disease diagnosis, determining eligibility for amyloid-targeting therapies, and quantifying treatment-related amyloid clearance. In settings where available, tau PET informs biological stage, prognosis, and clinical heterogeneity. MRI remains indispensable for differential diagnosis, the assessment of comorbid and vascular pathology, and monitoring for complications, particularly amyloid-related imaging abnormalities. Technological advances-including quantitative imaging, artificial intelligence, accelerated acquisition, and workflow optimisation-are improving reliability, efficiency, and access to these tools. Neuroimaging is now a cornerstone of Alzheimer's disease care and a crucial discriminator tool for characterising brain injury across the lifespan. With emerging fluid biomarkers, neuroimaging supports accurate diagnosis, prognosis, and treatment monitoring.
BMJ case reportsSyed Adil Hassan, Kasturi Hazarika, Prashant Kumar Rai
Dermatomyositis is a recognised paraneoplastic inflammatory myopathy although its association with oesophageal malignancy is uncommon. Most reported cases either precede or accompany the initial diagnosis of malignancy. We report a man in his late fifties with previously treated oesophageal squamous cell carcinoma who developed florid dermatomyositis after approximately 6 years of sustained remission following chemotherapy, radiotherapy and pembrolizumab therapy. He presented with progressive proximal muscle weakness, dysphagia and characteristic cutaneous manifestations accompanied by markedly elevated creatine kinase levels. Fluorodeoxyglucose positron emission tomography-CT demonstrated metastatic oesophageal squamous cell carcinoma involving the thoracic oesophagus, abdominal lymph nodes and liver. Corticosteroids followed by paclitaxel-carboplatin rechallenge chemotherapy resulted in marked improvement in both inflammatory manifestations and tumour burden. The chronology was notable for parallel evolution of inflammatory activity and metastatic disease after prolonged oncological remission.
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) >3 cm often recurs after resection, indicating a need for better risk stratification. The 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) maximum standardized uptake value (SUVmax) reflects tumor aggressiveness. We evaluated the prognostic significance of preoperative FDG-PET SUVmax in patients with resectable initial HCC >3 cm. PATIENTS AND METHODS: This retrospective analysis included 136 patients who underwent curative resection for HCC >3 cm between 2012 and 2021 with preoperative FDG-PET imaging. Patients were classified into low- and high-uptake groups based on tumor SUVmax. Associations between FDG-PET findings and clinicopathological factors were analyzed. RESULTS: Patients with high SUVmax had significantly worse overall survival than those with low SUVmax (49.2% vs. 90.0%, p<0.0001). Multivariate analysis identified high SUVmax as an independent predictor of poor overall survival (hazard ratio=3.16, 95% confidence interval=1.42-7.03, p=0.0048). Furthermore, recurrence-free survival was significantly worse in the high SUVmax group (33.4% vs. 60.4%, p=0.0006). High SUVmax was strongly associated with microscopic vascular invasion (MVI). Combining SUVmax with alpha-fetoprotein improved preoperative prediction of MVI. CONCLUSION: Preoperative FDG-PET SUVmax is an independent prognostic biomarker in HCC >3 cm and, when combined with serum alpha-fetoprotein, may enhance prediction of MVI. These findings support incorporating metabolic imaging into preoperative risk models to guide management.
Human brain mappingTimothy Lawn, Johan Nakuci, Steve C R Williams, Federico Turkheimer, Mitul A Mehta
Analyses of neuroimaging data increasingly leverage the distribution of neurotransmitter receptors derived from positron emission tomography (PET) to bridge the gap between micro- and macro-scale brain function. However, these receptor maps are highly spatially overlapping, which can give rise to interpretive and analytical challenges. Here, we systematically investigate the impact of spatial collinearity among PET maps in the context of Receptor-Enriched Analysis of functional Connectivity by Targets (REACT), a method that uses receptor maps as spatial regressors to derive subject-level molecular-enriched functional connectivity networks. Exhaustive combinatorial analysis across 19 receptor and transporter maps showed that collinearity scales rapidly with the number of receptors modelled simultaneously, and that the underlying correlation structure was relatively stable across parcellation scales, reflecting the intrinsic organisation of neurotransmitter systems. Using test-retest fMRI data from the Human Connectome Project, we demonstrate that modelling greater numbers of receptors degrades the reliability of molecular-enriched networks derived from conventional multivariate REACT models, and that collinearity among receptor maps drives this degradation. An alternative univariate approach, in which each receptor is modelled independently, yielded more reliable networks and, when applied to a within-subjects study of LSD compared to placebo, better recovered the role of the 5-HT2A receptor in LSD's neural effects. These findings identify spatial collinearity as a fundamental constraint on multivariate molecular-enriched network estimation. We therefore recommend univariate models as the default, with multivariate models used only where specifically motivated and reported alongside the univariate result.
Alzheimer's & dementia : the journal of the Alzheimer's AssociationLuyue Zhang, Ana M Franceschi, John F Crary, Frank A Provenzano, Alzheimer's Disease Neuroimaging Initiative
INTRODUCTION: Early neurofibrillary tau degeneration in the entorhinal cortex (EC) is a hallmark of Alzheimer's disease (AD) and aging. We propose a biomechanical cascade hypothesis, suggesting proximity to the tentorial incisura (TI) may render the EC susceptible to chronic mechanical stress, potentially contributing to tau pathology. METHODS: We developed a neuroanatomical contact coefficient (NCC) to quantify EC-TI proximity using Alzheimer's Disease Neuroimaging Initiative multimodal imaging data (n = 47), stratifying participants into high and low adjacency groups. RESULTS: Controlling for risk factors, EC tau positron emission tomography signal predicted conversion from mild cognitive impairment to AD only in the high-adjacency group (P = 0.036). DISCUSSION: Findings identify EC-TI proximity as a potential, novel, anatomically grounded biomarker of AD risk. These findings are consistent with a previously unrecognized biomechanical contribution to EC tau vulnerability in sporadic AD and aging, opening new avenues for early detection, risk stratification, and mechanistically targeted prevention strategies.
Alzheimer's & dementia : the journal of the Alzheimer's AssociationIsabella Bizzi, Arthur C Macedo, Lydia Trudel, Joseph Therriault, Nesrine Rahmouni, Firoza Z Lussier, Cécile Tissot, Gleb Bezgin, Étienne Aumont, Tevy Chan, Se…
INTRODUCTION: We compared the association between mild behavioral impairment (MBI) and first- versus second-generation tau-positron emission tomography (PET) tracers in preclinical and prodromal Alzheimer's disease (AD). METHODS: We assessed 110 individuals with head-to-head [18F]MK6240 and [18F]Flortaucipir tau-PET. Voxel-wise and region-of-interest analyses investigated relationships between tau-PET and MBI Checklist (MBI-C) scores, which were also compared across tau-PET positivity and PET-Braak stages. RESULTS: For both tracers, MBI severity was associated with tau-PET signal in all Braak regions and increased across PET-Braak stages. [18F]MK6240 showed more extensive voxel-wise associations with MBI-C scores and additional correlations with affective symptoms in stratified analyses by diagnostic groups. Tau positivity was associated with a higher frequency of MBI. Individuals positive for [18F]MK6240 but negative for [18F]Flortaucipir exhibited greater MBI burden than individuals negative for both tracers. DISCUSSION: MBI in early AD is associated with tau-PET, with [18F]MK6240 providing greater sensitivity to detect MBI-related symptoms.
Human brain mappingClaudia Tarricone, Giulia Vallini, Giorgia Baron, Massimiliano Facca, Erica Silvestri, Tommaso Volpi, Andrei G Vlassenko, Manu S Goyal, Alessandra Bertoldo
Despite accounting for only 2% of body weight, the human brain requires significant amounts of glucose, even at rest, underscoring the importance of functional-metabolic relationships. Previous studies revealed moderate associations between resting-state fMRI functional connectivity (FC) and local metabolism via [18F]FDG-PET, yet much remains to be understood, particularly regarding their coupling between functional and metabolic networks. To this end, we employed multivariate Partial Least Squares Correlation (PLSC) to investigate the functional-metabolic relationship at both nodal and network levels. From dynamic [18F]FDG-PET data we estimated parameters describing glucose metabolism-delivery rate (K1), phosphorylation rate (k3), and fractional uptake (Ki)-and generated within-individual metabolic connectivity (MC) networks. FC was derived from fMRI data filtered into two frequency bands and summarized as region-wise strength to capture nodal characteristics. Our findings revealed that glucose delivery is linked with FC strength, particularly when fMRI signal frequencies include greater hemodynamic contributions. Even stronger functional-metabolic coupling occurs at the network level in the low-frequency fMRI band, with higher MC between sensory/attention and transmodal networks supporting stronger FC within sensory/attention areas. By leveraging PLSC, this work deepens our understanding of the functional-metabolic synergy in the healthy brain, providing new insights into its organization.
Current cardiology reportsMassimo Imazio, Francesco Venturelli, Valentino Collini
PURPOSE OF REVIEW: Cardiac sarcoidosis (CS) is an inflammatory granulomatous cardiomyopathy associated with atrioventricular block, ventricular arrhythmias, heart failure (HF), and sudden cardiac death (SCD). Diagnosis and management remain challenging because myocardial involvement is patchy and evidence from randomized trials is limited. This review summarizes current knowledge on CS, focusing on advances in diagnosis, immunosuppression, and prevention of arrhythmic events. RECENT FINDINGS: Cardiac involvement is clinically recognized in 5-10% of patients with sarcoidosis but is more frequent in imaging and autopsy studies. Cardiac magnetic resonance (CMR) and ^18F-fluorodeoxyglucose positron emission tomography (FDG-PET) provide complementary information on myocardial scar and active inflammation. Multimodality imaging, extracardiac tissue diagnosis, guided endomyocardial biopsy, and consensus criteria improve diagnostic confidence. Corticosteroids remain first-line therapy for active inflammation, while steroid-sparing agents are increasingly used to reduce corticosteroid exposure or treat persistent disease. Inflammasome/interleukin-1 inhibition is an emerging targeted strategy, but its clinical efficacy remains unproven. SCD risk stratification now extends beyond left ventricular ejection fraction to include ventricular arrhythmias, conduction disease, ventricular dysfunction, and myocardial scar burden. Implantable cardioverter-defibrillator therapy remains central in selected high-risk patients. CS requires early recognition of both inflammation and myocardial scar. CMR and FDG-PET are central to diagnosis, prognosis, and therapeutic decisions, while management combines immunosuppression, HF therapy, and arrhythmia prevention. Major uncertainties remain regarding optimal diagnostic criteria, immunosuppression strategies, serial imaging, and primary-prevention ICD selection. Prospective studies and randomized trials are needed to refine treatment and risk stratification.
Physics in medicine and biologyLaura Moliner, Carlos Correcher, Adrian Beltrá, Cesar Molinos, Todd Sasser, Alejandro Lucero, Keshav Nagpal, Noriel Pavón, Michael Heidenreich, Jose María Benl…
Objective.This work presents a comprehensive evaluation of the Bruker PET/CT Si78 preclinical imaging system, combining standardized performance assessment, inter-system reproducibility analysis, and investigation of depth-of-interaction (DOI) encoding effects on image quality.Approach.Ten independently assembled systems were characterized following the National Electrical Manufacturers Association NU 4-2008 protocol to assess spatial resolution, sensitivity, count rate performance, and image quality. Beyond standard evaluation, this study investigates the impact of DOI estimation using simulations, controlled experiments, andin vivomulti-mouse imaging.Main results.The results demonstrate consistent performance across the evaluated systems, with nearly uniform spatial resolution across the field of view (FOV), peak sensitivity around 10.5%, and low variability among systems, typically below 5%, indicating low inter-system variability across most evaluated metrics-. Continuous DOI estimation, enabled by monolithic detector technology, improves spatial resolution and its uniformity compared with dual-layer and non-DOI approaches, particularly at the periphery of the imaging volume where parallax effects are most pronounced. These improvements were consistently observed in both simulated and experimental datasets. The practical implications of DOI encoding were demonstrated in multi-animal imaging studies, where enhanced visualization of fine anatomical structures and improved quantitative accuracy were achieved. In particular, the absence of DOI information led to substantial spatially dependent quantification errors, while dual-layer DOI partially mitigated these effects. Continuous DOI estimation provided the smallest deviations and most spatially uniform results among the evaluated configurations, supporting reliable quantification in demanding applications such as brain imaging. Significance. Overall, the PET/CT Si78 system combines competitive performance with high reproducibility and advanced DOI capabilities, enabling uniform image quality across the FOV and supporting efficient multi-animal studies. These characteristics supports its use for reproducible and ethically optimized preclinical imaging aligned with the principles of reduction and refinement in animal research.
World journal of urologyJ Gómez Rivas, L Fernández Hernández, L Turpin, A Peyrottes, M Rouprêt
PURPOSE: To examine the gap between evidence-based indications for PSMA PET/CT and real-world access in prostate cancer, with a focus on European implementation and country-specific experience from Spain and France. METHODS: A focused narrative appraisal of published evidence, clinical guidelines, regulatory and reimbursement information, and real-world accessibility data was performed. European accessibility modelling and physician market research from Spain were incorporated to characterise implementation patterns and barriers. RESULTS: Access to PSMA PET/CT remains heterogeneous despite its established role in higher-risk staging and biochemical recurrence. Reported barriers include reimbursement and local approval requirements, PET/CT and nuclear medicine capacity, radiopharmaceutical logistics, non-standardised referral pathways, waiting times, and institutional variation. Exploratory modelling suggested that use remains below the estimated eligible population in both staging and biochemical recurrence, with differences between countries and clinical scenarios. Spanish market research similarly indicated substantial variation. These data are exploratory implementation signals rather than population-level epidemiological estimates. CONCLUSION: Improving access requires guideline-based eligibility criteria, harmonised reimbursement, regional referral networks, adequate imaging and reporting capacity, reliable tracer supply, and measurable access indicators. Further research should determine whether reducing implementation gaps improves diagnostic pathways and treatment allocation.
Proceedings of the National Academy of Sciences of the United States of AmericaDardo Tomasi, Nora D Volkow
Large-scale functional connectivity gradients provide a compact description of cortical organization, capturing hierarchical transitions from unimodal sensory systems to transmodal association cortex. Although these gradients have become a central framework for studying macroscale brain organization, it remains unclear whether they systematically map onto regional cortical biology. Here we show that functional gradient position robustly predicts cortical thickness and regional glucose metabolism, measured with MRI and FDG-PET respectively. Modeling parcelwise cortical thickness and glucose metabolism as linear combinations of signed and amplitude components along functional gradients explained substantial variance in both measures across individuals, with signed gradient terms improving prediction in every subject. These relationships generalized across scanning sessions and independent cohorts and remained significant under spatial permutation testing. Gradient-based models outperformed classical graph-theoretic connectivity metrics, whereas nonlinear extensions did not improve performance. Cortical myelin was selectively associated with the signed component of the principal gradient, without an amplitude effect, and this pattern replicated across developmental, adult, and aging cohorts, supporting a microstructural basis for gradient-cortical thickness coupling. In contrast, gradient associations with glucose metabolism remained largely intact after controlling for myelination, indicating additional biological determinants. These findings establish functional gradients as a reproducible framework linking cortical hierarchy to structure and metabolism.
Neurology(R) neuroimmunology & neuroinflammationArian Madani Neishaboori, Mansi Agarwal, Ally Kalinsky, Justin P Lofaso, Gayatri Rampilla, Elizabeth A Kras, Sydney C Nagy, John G Cooper, Shenjian Ai, Claire …
BACKGROUND AND OBJECTIVES: PET imaging targeting the 18-kDa translocator protein (TSPO) is a widely used method to detect neuroinflammation in vivo and shows promise for detecting innate inflammatory activity in multiple sclerosis (MS). However, TSPO-PET findings in MS vary substantially across studies. We performed a systematic review and meta-analysis to quantify TSPO-PET signal differences between people with MS (PwMS) and healthy controls (HCs) and to evaluate the impact of methodological factors on study outcomes. METHODS: A systematic search of Scopus, MEDLINE, Web of Science, and Embase databases was conducted through September 10, 2025. Original TSPO-PET studies in PwMS were included. Standardized mean differences (SMDs) in TSPO-PET signal between PwMS and HC were pooled using random-effects models with cluster robust variances. Heterogeneity was assessed using I2 statistics. Meta-regression and subgroup analyses investigated methodological sources of heterogeneity. Patient-level data were analyzed for associations with clinical and demographic variables. Risk of bias and certainty of evidence were assessed using quality assessment of diagnostic accuracy studies 2 tool and GRADE framework, respectively. RESULTS: Forty-nine studies met inclusion criteria. Overall meta-analysis revealed significantly increased TSPO-PET signal in PwMS vs HC (SMD = 0.44, 95% CI: 0.27-0.61, p = 0.0002, I2: 97.00%). TSPO-PET signal was also significantly higher in progressive MS than in relapsing-remitting MS, indicating discrimination across MS clinical subtypes. Meta-regression attributed study heterogeneity to tracer (11.47%), PET quantification method (15.37%), and region of interest (19.71%) differences. Significant PwMS vs HC differences were most consistently observed with select tracers ([11C]PBR28, [18F]DPA-714, [11C]ER176, and [11C]PK11195) and with distribution volume ratio (DVR), nondisplaceable binding potential (BPND), and standardized uptake value ratio metrics. Significant effects were found in perilesional, thalamic, cortical, hippocampal, normal-appearing white matter, and T2-weighted white matter lesion regions. Patient-level analyses, while limited in power, showed significant associations between TSPO-PET signal (DVR) and disability measures (expanded disability status scale). DISCUSSION: TSPO-PET effectively distinguishes PwMS from HC and differentiates MS subtypes. However, radiotracer, quantification method, image analysis method, reference tissue, and region of interest significantly impact TSPO-PET outcomes and must be considered when designing and interpreting studies. Methodological standardization and improved reporting will be essential to enhance cross-study comparability and clinical interpretability.
Current neurology and neuroscience reportsJan Kassubek, Hans-Peter Müller
PURPOSE OF REVIEW: The review is intended to summarize and discuss the increasing roles and perspectives of neuroimaging in the clinical and scientific work-up of amyotrophic lateral sclerosis (ALS) and other motor neuron diseases (MND). RECENT FINDINGS: The applications of magnetic resonance imaging (MRI) and positron emission tomography (PET) identify characteristic disease-specific patterns especially for ALS including its clinical subtypes. Guided by neuroanatomical pattern stratification, these MND-associated alterations could be detected by dedicated analysis parameters from MRI, including T1-weighted structural imaging and microstructural diffusion tensor imaging, in combination with additional MR techniques, to act as diagnostic and monitoring biomarkers. Imaging in MND increasingly makes use of machine learning-based analysis methods. The conceptualization of (neuro-)imaging in ALS and other MND encompasses multiparametric technical approaches, also of regions outside the central nervous system, together with aspects of disease-specific pathophysiology which will further advance the field in future applications.
Journal of radiological protection : official journal of the Society for Radiological ProtectionKanokon Poonak, Poonnaphob Sopapan, Phiyada Thongkuam, Marisa Sureeyaphan, Ladawan Tanakitchaiyasit, Nopteera Sungsriphet, Panatsada Awikunprasert, Piyarat Par…
Occupational radiation protection in nuclear medicine is complicated by ambient radiation fields that vary both spatially and temporally. This variability arises from routine radiopharmaceutical handling and from patients who act as temporary mobile radiation sources after administration. Passive dosimetry provides cumulative information but cannot resolve short-term fluctuations arising during routine operations. This study integrated fixed-location optically stimulated luminescence (OSL) dosimetry with time-resolved Geiger-Müller monitoring to characterise spatial variations in ambient dose equivalent and temporal variations in dose-rate in a clinical nuclear medicine department. Monthly ambient dose equivalent,H*(10), was measured at 34 positions grouped into 14 functional areas across controlled, supervised, and uncontrolled zones, while ambient dose rate was recorded at 1 s intervals during routine working hours (08:00-16:00 h) over four weeks. Location-based estimates of annual effective dose (AED) and excess lifetime cancer risk were derived from the OSL measurements. At the functional-area level, the syringe placement area showed the highest monthlyH*(10) (0.405 mSv month-1), followed by the patient waiting room (0.288 ± 0.214 mSv month-1) and injection room (0.204 ± 0.101 mSv month-1). The patient waiting room also recorded the highest four-week mean dose rate (1.21 ± 0.24µSv h-1). Functional-area AED indicators ranged from 1.18 to 5.30 mSv y-1, reflecting spatial variation in the annualised exposure estimates.H*(10) did not differ significantly among the three zones (p= 0.262), it differed significantly among locations within the controlled zone (p= 0.046). Time-resolved monitoring further revealed transient dose-rate peaks that were not apparent in cumulative dosimetry. Integrated monitoring may provide a more comprehensive basis for spatial prioritization and workflow-informed optimisation of radiation protection.
BMJ case reportsLakshmi Kandhan L, Venkata Ramana K, Rubina Singh, Raghavendran Asokan, Chandru Thirunavukkarasu, Natarajan K
Ewing's sarcoma is an aggressive small round cell tumour that usually arises from bone or soft tissues in children and young adults. Primary origin within the prostate is exceptionally rare, with only isolated cases documented. We describe a man in his 20s who presented with urinary obstruction, constipation and leg pain. Imaging revealed a bulky pelvic mass arising from the prostate and bilateral hydroureteronephrosis. Histology demonstrated a round cell neoplasm with strong CD99 and FLI1 positivity, confirming Ewing's sarcoma. Staging PET-CT identified widespread metastases involving lung, liver and bone. The patient underwent urinary and bowel diversion, followed by Vincristine, Adriamycin, Cyclophosphamide alternating with Ifosfamide and Etoposide (VAC/IE) chemotherapy. He achieved complete metabolic remission, allowing colostomy reversal and is currently under surveillance. This case illustrates the need to consider rare sarcomas in the differential diagnosis of pelvic masses in young men with normal serum PSA and highlights the potential for durable response with timely systemic therapy.
Molecular neurodegenerationJohannes Gnörich, Julia Kusche-Palenga, Agnes Kling, Amir Dehsarvi, Angela Bronte, Lukas Frontzkowski, Artem Zatcepin, Mirlind Zaganjori, Florian Schöberl, Seb…
BACKGROUND: Patients with Alzheimer's disease (AD) and clinically overlapping neurodegenerative diseases are classified molecularly using the A/T/N classification system. Apart from fluid biomarkers and structural MRI, A/T/N assessment incorporates β-amyloid-PET (A), tau-PET (T), and [18F]FDG-PET (N). We evaluated if dynamic features of tau-PET with [18F]PI-2620 allow prediction of β-amyloid positivity and simultaneous staging of tau and neurodegeneration in individual patients using a single imaging session. METHODS: We studied 129 patients with tauopathies, comprising 47 patients with β-amyloid-positive 3/4-repeat tauopathy and 82 patients with β-amyloid-negative primary 4-repeat tauopathies, alongside 17 healthy controls. Participants underwent 60-minute dynamic [18F]PI-2620 tau-PET. Kinetic modelling simultaneously provided tracer efflux rate (K2a) as a predictor for β-amyloid status, distribution volume ratio (DVR) for regional tau burden, and relative perfusion (R1) as a marker of neurodegeneration. These parameters were validated against β-amyloid-PET, [18F]FDG-PET, volumetric MRI, and cerebrospinal fluid biomarkers using receiver operating characteristic and correlation analyses and visual assessments. [18F]PI-2620K2a-based prediction of β-amyloid positivtiy was additionally tested in an independent, clinically heterogeneous validation cohort of 97 individuals. RESULTS: [18F]PI-2620K2a differentiated tau isoform compositions despite clinically overlapping presentations and tau-PET patterns, demonstrating reduced cortical tracer clearance in 3/4-repeat compared with 4-repeat tauopathies. [18F]PI-2620K2a remained sensitive in individuals with visually negative or low [18F]PI-2620DVR signals and outperformed both tau burden and perfusion for predicting β-amyloid status, achieving an area under the curve of 0.99, a positive predictive value of 91.5%, and a negative predictive value of 95.1%. Performance remained robust in the independent validation cohort, with an area under the curve of 0.98, a positive predictive value of 87.9%, and a negative predictive value of 95.3%. [18F]PI-2620DVR quantified regional tau patterns, with cortical predominance in 3/4-repeat tauopathy and subcortical involvement in 4-repeat tauopathies. [18F]PI-2620R1 exhibited strong quantitative and visual associations with established markers of neurodegeneration. Integration of K2a, DVR, and R1 in disease-specific composite regions enabled individualized three-dimensional A/T/N staging. CONCLUSIONS: Dynamic [18F]PI-2620 PET imaging facilitates assessment of the β-amyloid status and regional staging of tau and neurodegeneration during a single acquisition. This one-stop-shop approach may reduce radiation exposure, streamline diagnostic workflows, and facilitate personalized disease profiling.
BMJ case reportsMargaux Mouchet, Jolanta Gourmaud, Mohammed Ehab Kamel, Marie-Gabrielle Courtès
Immune checkpoint inhibitor (ICI)-induced pancreatitis is a rare immune-related adverse event that can present as mass-forming lesions mimicking metastatic disease, posing a diagnostic challenge in patients with cancer. We report the case of a woman with early triple-negative breast cancer who, after 4 months of neoadjuvant chemoimmunotherapy, experienced progression of the primary tumour. Restaging PET-CT revealed four hypermetabolic pancreatic lesions, suggestive of metastases. Abdominal MRI confirmed the presence of pancreatic masses. Endoscopic ultrasound-guided biopsy revealed immune-related pancreatitis with no malignant cells. Laboratory workup showed elevated amylase and lipase levels despite the patient being asymptomatic. ICI was discontinued and corticosteroid therapy was initiated, with normalisation of pancreatic enzymes. After excluding metastatic spread, the patient underwent a total mastectomy for local progression. This case highlights that ICI-induced pancreatitis can mimic metastatic disease and that tissue biopsy is essential to avoid misdiagnosis and inappropriate treatment escalation.
This pilot trial evaluated the one-year tolerability of oral N-acetylcysteine (NAC) 1200 mg/day in Parkinson's disease (PD) and explored associations with clinical progression, levodopa dose, and striatal dopamine-transporter imaging. Forty-two patients were randomized to NAC or matching placebo twice daily for 12 months in addition to usual care. Completers (n = 32) were assessed at baseline and 12 months with the original UPDRS parts I-IV, 99mTc-TRODAT-1 SPECT, prescribed levodopa dose, and liver/kidney tests. Analyses included paired t-tests, Welch tests of change scores, and linear mixed-effects models with a group × time interaction adjusted for age, sex, and disease duration. No multiplicity correction was applied; results are exploratory. Thirty-two of 42 randomized patients completed both visits. Total UPDRS increased in both groups, but less with NAC than placebo (mean Δ + 5.4 vs. + 9.5 points; difference - 4.1, 95% CI - 7.6 to - 0.5; p = 0.028; mixed-model group × time p = 0.024). Mood-item change also differed (difference - 0.64, 95% CI - 1.17 to - 0.11; p = 0.020). TRODAT binding declined less with NAC (difference in change + 5.5 units, 95% CI 1.7 to 9.3; p = 0.006; group × time p = 0.004). The ≤ 4-year subgroup comprised 9/17 (53%) NAC and 7/15 (47%) placebo participants and showed a similar pattern. Levodopa-dose change was not significant between groups after ANCOVA adjustment for baseline dose, age, sex, and disease duration (adjusted difference - 86 mg/day, 95% CI - 235 to + 64; p = 0.25). Completer laboratory values were stable; discontinuations were not characterized for adverse events. One-year oral NAC was associated with more favorable exploratory clinical and imaging trajectories than placebo. Completer laboratories were unremarkable, but safety cannot be established from completers alone. These data do not establish disease modification and require confirmation in a larger, prospectively powered trial.